The Best Anticoagulation Therapy in Multiple-Trauma Patients with Mechanical Heart Valves: Evaluation of Latest Guidelines and Studies.

PubMed

Moeinipour, Aliasghar; Zarifian, Ahmadreza; Sheikh Andalibi, Mohammad Sobhan; Shamloo, Alireza Sepehri; Ahmadabadi, Ali; Amouzeshi, Ahmad; Hoseinikhah, Hamid

2015-12-22

It is common practice for patients with prosthetic cardiac devices, especially heart valve prosthesis, arterial stents, defibrillators, and pacemaker devices, to use anticoagulation treatment. When these patients suffer from multiple trauma after motor vehicle accidents, the best medical management for this challenging position is mandatory. This strategy should include a rapid diagnosis of all possible multiple organ injuries, with special attention to anticoagulation therapy so as to minimize the risk of thromboembolism complication in prosthetic devices. In this review, we describe the best medical management for patients with multiple trauma who use anticoagulants after heart valve replacement. We searched electronic databases PubMed/Medline, Scopus, Embase, and Google Scholar using the following terms: anticoagulant, warfarin, heparin, and multiple trauma. Also, similar studies suggested by the databases were included. Non-English articles were excluded from the review. For patients who use anticoagulation therapy, teamwork between cardiac surgeons, general surgeons, anesthesiologists, and cardiologists is essential. For optimal medical management, multiple consults between members of this team is mandatory for rapid diagnosis of all possible damaged organs, with special attention to the central nervous system, chest, and abdominal traumas. With this strategy, it is important to take note of anticoagulation drugs to minimize the risk of thromboembolism complications in cardiac devices. The best anticoagulant agents for emergency operations in patients with multiple trauma who are using an anticoagulant after heart valve replacement are fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC).

iPod™ technology for teaching patients about anticoagulation: a pilot study of mobile computer-assisted patient education.

PubMed

Denizard-Thompson, Nancy R; Singh, Sonal; Stevens, Sheila R; Miller, David P; Wofford, James L

2012-01-01

To determine whether an educational strategy using a handheld, multimedia computer (iPod™) is practical and sustainable for routine office-based patient educational tasks. With the limited amount of time allotted to the office encounter and the growing number of patient educational tasks, new strategies are needed to improve the efficiency of patient education. Education of patients anticoagulated with warfarin is considered critical to preventing complications. Despite the dangers associated with the use of warfarin, educational practices are variable and often haphazard. During a four-month period, we examined the implementation of a three-part series of iPod™-based patient educational modules delivered to anticoagulated patients at the time of routine INR (International Normalized Ratio) blood tests for outpatients on the anticoagulation registry at an urban community health center. A total of 141 computer module presentations were delivered to 91 patients during the four-month period. In all, 44 patients on the registry had no INR checkups, and thus no opportunity to view the modules, and 32 patients had at least three INR checkups but no modules were documented. Of the 130 patients with at least one INR performed during the study period, 22 (16.9%) patients completed all three modules, 91 (70.0%) patients received at least one module, and nine (7.6%) patients refused to view at least one module. Neither of the two handheld computers was lost or stolen, and no physician time was used in this routine educational activity. Patients reported that the audio and visual quality was very good, (9.0/10); the educational experience of the patient was helpful (7.4/10) compared with the patient's previous warfarin education (6.3/10), and the computer strategy extended the INR visit duration by 1-5 min at most. The computer-assisted patient educational strategy was well received by patients, and uptake of the intervention by the clinic was successful and durable. The iPod™ strategy standardized the educational message, improved clinic efficiency, and helped this busy clinic meet its educational goals for patient education.

The Reversal of Direct Oral Anticoagulants in Animal Models

PubMed Central

Honickel, Markus; Akman, Necib; Grottke, Oliver

2017-01-01

ABSTRACT Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity). Though promising, most specific antidotes are still in development. Preclinical animal research is the key to establishing the efficacy and safety of potential reversal agents. Here, we summarize published preclinical animal studies on reversal of DOAC anticoagulation. These studies (n = 26) were identified via a PubMed search, and used rodent, rabbit, pig, and non-human primate models. The larger of these animals have the advantages of similar blood volume/hemodynamics to humans, and can be used to model polytrauma. We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies. PMID:28471371

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Aspirin in stroke prevention in nonvalvular atrial fibrillation and stable vascular disease: an era of new anticoagulants.

PubMed

Turagam, Mohit K; Velagapudi, Poonam; Leal, Miguel A; Kocheril, Abraham G

2012-04-01

Atrial fibrillation (AF) is a major cause of ischemic stroke, especially in the elderly. There are currently enough data to support the notion that anticoagulation with warfarin or dabigatran is far superior to aspirin in the prevention of stroke or systemic embolism in AF. Aspirin is the preferred modality in patients who are either not candidates for anticoagulation, such as patients with increased risk for bleeding, low-risk patients based on the CHADS2 score or patients who have difficulty in maintaining a therapeutic international normalized ratio. There is no dispute on the recommendations regarding stroke prevention in high-risk patients (CHADS2 risk score of 2 and beyond) with AF. However, there is some controversy regarding the appropriate strategy (anticoagulation vs aspirin) for stroke prevention in low-risk patients (CHA2DS2-VASc score of 0-1). Novel oral anticoagulant drugs (direct thrombin inhibitors and Factor Xa inhibitors) might further diminish the role of aspirin for stroke prevention in AF due to their superior efficacy, lack of need for monitoring of therapeutic effects and lower bleeding risk when compared with warfarin, especially in patients with stable vascular disease.

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

PubMed

Lyle, Courtney A; Sidonio, Robert F; Goldenberg, Neil A

2015-02-01

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Management Strategy for Patients With Chronic Subclavian Vein Thrombosis.

PubMed

Keir, Graham; Marshall, M Blair

2017-02-01

We performed a systematic review to determine best practice for the management of patients with chronic or subacute subclavian vein thrombosis. This condition is best managed with surgical excision of the first rib followed by long-term anticoagulation. Interventional techniques aimed at restoring patency are ineffective beyond 2 weeks postthrombosis. Additional therapeutic options should be made based on the severity of symptoms as well as vein status. Patients with milder symptoms are given decompression surgery followed by anticoagulation whereas patients with more severe symptoms are considered for either a jugular vein transposition or saphenous patch based on the vein characteristics. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

PubMed

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2018-02-01

The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

Residual vein thrombosis and serial D-dimer for the long-term management of patients with deep venous thrombosis.

PubMed

Prandoni, Paolo; Vedovetto, Valentina; Ciammaichella, Maurizio; Bucherini, Eugenio; Corradini, Sara; Enea, Iolanda; Cosmi, Benilde; Mumoli, Nicola; Visonà, Adriana; Barillari, Giovanni; Bova, Carlo; Quintavalla, Roberto; Zanatta, Nello; Pedrini, Simona; Villalta, Sabina; Camporese, Giuseppe; Testa, Sofie; Parisi, Roberto; Becattini, Cecilia; Cuppini, Stefano; Pengo, Vittorio; Palareti, Gualtiero

2017-06-01

The optimal long-term strategy for preventing recurrent venous thromboembolism (VTE) in patients with deep-vein thrombosis (DVT) is uncertain. In 620 consecutive outpatients with a first proximal DVT who had completed at least three months of anticoagulation (unprovoked in 483, associated with minor risk factors in 137), the ultrasound presence of residual vein thrombosis (RVT) was assessed and defined as an incompressibility of at least 4mm. In 517 patients without RVT and with negative D-dimer, anticoagulation was stopped and D-dimer was repeated after one and three months. Anticoagulation was resumed in 63 of the 72 patients in whom D-dimer reverted to positivity. During a mean follow-up of three years, recurrent VTE developed in 40 (7.7%) of the 517 patients, leading to an annual rate of 3.6% (95% CI, 2.6 to 4.9): 4.1% (95% CI, 2.9 to 5.7) in individuals with unprovoked DVT, and 2.2% (95% CI, 1.1 to 4.5) in those with DVT associated with minor risk factors. Of the 233 males with unprovoked DVT, 17 (7.3%) developed events in the first year of follow-up. Major bleeding complications occurred in 8 patients while on anticoagulation, leading to an annual rate of 1.2% (95% CI, 0.6 to 2.4). Discontinuing anticoagulation in patients with a first episode of proximal DVT based on the assessment of RVT and serial D-dimer leads to an overall annual rate of recurrent VTE lower than 5.0%, which is the rate deemed as acceptable by the Subcommittee on Control of Anticoagulation of the ISTH. However, in males with unprovoked DVT there is room for further improving the long-term strategy of VTE prevention. (ClinicalTrials.gov number, NCT01285661). Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of Guidelines for Reducing Stroke Risk in Patients With Nonvalvular Atrial Fibrillation: A Review From a Latin American Perspective

PubMed Central

Silva, Gisele Sampaio; Ameriso, Sebastián F.

2017-01-01

Atrial fibrillation (AF) is a prominent risk factor for stroke and a leading cause of death and disability throughout Latin America. Contemporary evidence-based guidelines for the management of AF and stroke incorporate the use of practical and relatively simple scoring methods to estimate both stroke and bleeding risk, in order to assist in matching patients with appropriate interventions. This review examines consistencies and differences among guidelines for reducing stroke risk in patients with AF, assessing the role of user-friendly scoring methods to determine appropriate patients for anticoagulation and other treatment options. Current options include warfarin and direct oral anticoagulants such as dabigatran, rivaroxaban, apixaban, and edoxaban. These agents have been found to be superior or noninferior to standard vitamin K antagonist anticoagulation in large randomized trials. Potential benefits of these agents mainly include lower ischemic stroke rates, reduced intracranial bleeding, no need for regular monitoring, and fewer drug–drug and drug–food interactions. Expert opinions regarding clinical situations for which data are presently lacking, such as emergency bleeding and stroke in anticoagulated patients, are also provided. Enhanced attention and adherence to evidence-based guidelines are essential components for a strategy to reduce stroke morbidity and mortality across Latin America. PMID:28992764

Applying the cell-based coagulation model in the management of critical bleeding.

PubMed

Ho, K M; Pavey, W

2017-03-01

The cell-based coagulation model was proposed 15 years ago, yet has not been applied commonly in the management of critical bleeding. Nevertheless, this alternative model may better explain the physiological basis of current coagulation management during critical bleeding. In this article we describe the limitations of the traditional coagulation protein cascade and standard coagulation tests, and explain the potential advantages of applying the cell-based model in current coagulation management strategies. The cell-based coagulation model builds on the traditional coagulation model and explains many recent clinical observations and research findings related to critical bleeding unexplained by the traditional model, including the encouraging results of using empirical 1:1:1 fresh frozen plasma:platelets:red blood cells transfusion strategy, and the use of viscoelastic and platelet function tests in patients with critical bleeding. From a practical perspective, applying the cell-based coagulation model also explains why new direct oral anticoagulants are effective systemic anticoagulants even without affecting activated partial thromboplastin time or the International Normalized Ratio in a dose-related fashion. The cell-based coagulation model represents the most cohesive scientific framework on which we can understand and manage coagulation during critical bleeding.

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism.

PubMed

Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S

2017-08-01

Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this patient group. © 2017 International Society on Thrombosis and Haemostasis.

Effect of sodium citrate based anticoagulants on the growth activity of malaria parasites.

PubMed

Liu, Zhong-xiang; Wang, Xian-feng; Li, Shu-mei; Li, Xun; Xue, Cai-fang; Miao, Jun

2004-12-01

To study the effect of anticoagulants based on sodium citrate on the growth activity of malaria parasites. The parasites were treated with 3 anticoagulants (ACD, CD and SC), respectively, and the parasitemia was determined to measure the effect of the anticoagulants on the growth of the parasites. Unsynchronized Plasmodium falciparum was treated with the anticoagulants at different concentrations for 3 h at 37 degrees C. Treated erythrocytes were mixed with normal parasites or treated parasites with normal erythrocytes, which was followed by parasitemia determination of the two cultures to determine the cell target of the anticoagulants. Stage-synchronized parasites (ring, trophozoite and schizont) were treated as above to investigate the stage target. P. berghei was also treated with anticoagulants and inoculated in mice to detect the effect of anticoagulants on the animal malaria parasite by counting the parasitemia. All 3 anticoagulants inhibited falciparum parasite growth and ACD had the strongest potency. The treatments of the erythrocyte and the parasite with anticoagulants respectively showed that the anticoagulants targeted the parasites rather than normal erythrocytes. Stage-synchronized parasite treatment suggested anticoagulants primarily inhibited schizonts. The effect of anticoagulants on P. berghei was similar to that on P. falciparum. ACD showed the most significant inhibitive effect on the growth of malaria parasites and SC was the best anticoagulant based on sodium citrate for malarial experiments.

The Translation of Knowledge into Practice in the Management of Atrial Fibrillation in Singapore.

PubMed

Woo, Fong Yeong Brigitte; Lim, Toon Wei; Tam, Wai San Wilson

2018-03-12

Atrial fibrillation (AF) is a clinically significant cardiac arrhythmia known to increase the risk of stroke by at least four times. Stroke-risk assessment and thromboprophylaxis are vital components in AF management. Guidelines are available to standardise AF management, but physicians' adherence to the recommended guidelines has been low. The aims were to: 1. Examine and compare the level of knowledge and current practice in AF management between cardiologists and non-cardiologist physicians in Singapore; 2. Identify physicians' perceived barriers to prescribing oral anticoagulants (OACs) when indicated; 3. Identify strategies to optimise AF management. From June 2017 to August 2017, a cross-sectional online survey involving physicians was conducted in Singapore. The survey instrument was adapted from a previously developed instrument, and validated locally by five cardiologists. It explored the physicians' stroke-risk assessment practices, estimation of stroke risk and benefits of anticoagulation, likelihood of prescribing anticoagulation when indicated, perceived barriers to anticoagulation, and strategies to optimise AF management. Sixty-three physicians completed the survey (14 cardiologists and 49 non-cardiologist physicians). No significant difference was found between cardiologists and non-cardiologist physicians in their assessment and estimation of stroke risk for stable AF patients. However, when presented with an AF patient with stroke risk, cardiologists were more likely than non-cardiologist physicians to prescribe novel OACs (93% vs. 51%; χ 2 =7.933, p=0.004). Compared to cardiologists, the majority of the non-cardiologist physicians thought the risk of falls were usually or always barriers to prescribing OACs (29% vs 69%; χ 2 =7.579, p=0.006). Among the suggested strategies to support them in AF management, physicians have overwhelmingly rated two as "quite useful" and "very useful": the establishment of clinics for monitoring anticoagulated patients (100%); and involvement of pharmacists in managing patients on warfarin (98.4%). Physicians possess good knowledge about stroke-risk assessment in AF patients yet it is not translated into effective measures for stroke prevention. Physicians, especially non-cardiologist ones, were not anticoagulating AF patients when indicated. Although novel OACs are safer alternatives to warfarin, non-cardiologist physicians were less inclined to use them for stroke prevention. All physicians opined that establishing anticoagulation clinics and collaborating with pharmacists were useful strategies to optimise AF management. Existing barriers to anticoagulation impeded the translation of knowledge into practice in the management of AF patients in Singapore, for which optimal strategies to optimise AF management are ascertained. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation: an evidence-based choice.

PubMed

Li, Yan-Guang; Pastori, Daniele; Lip, Gregory Y H

2018-06-01

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomized trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomized trials are supplemented by effectiveness and safety data from real-world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC to the particular patient's characteristics, with the aim of optimizing outcomes for the individual patient. This review article aims to provide a summary of the evidence on the performance of NOACs in AF patients with specific clinical characteristics. Evidence-based suggestions are presented to provide a simple and viable strategy for clinicians for the choice of a particular NOAC. KEY MESSAGE Given the different performance of the new-oral anticoagulants in patients with the different clinical situation, evidence-based choice of fitting the right new-oral anticoagulants to the patients is provided in this review article.

Best strategies for patient education about anticoagulation with warfarin: a systematic review

PubMed Central

Wofford, James L; Wells, Megan D; Singh, Sonal

2008-01-01

Background Patient education is an essential component in quality management of the anticoagulated patient. Because it is time consuming for clinicians and overwhelming for patients, education of the anticoagulated patient is often neglected. We surveyed the medical literature in order to identify the best patient education strategies. Methods Study Selection: Two reviewers independently searched the MEDLINE and Google Scholar databases (last search March 2007) using the terms "warfarin" or "anticoagulation", and "patient education". The initial search identified 206 citations, A total of 166 citations were excluded because patients were of pediatric age (4), the article was not related to patient education (48), did not contain original data or inadequate program description (141), was focused solely on patient self-testing (1), was a duplicate citation (3), the article was judged otherwise irrelevant (44), or no abstract was available (25). Data Extraction: Clinical setting, study design, group size, content source, time and personnel involved, educational strategy and domains, measures of knowledge retention. Results Data Synthesis: A total of 32 articles were ultimately used for data extraction. Thirteen articles adequately described features of the educational strategy. Five programs used a nurse or pharmacist, 4 used a physician, and 2 studies used other personnel/vehicles (lay educators (1), videotapes (1)). The duration of the educational intervention ranged from 1 to 10 sessions. Patient group size most often averaged 3 to 5 patients but ranged from as low as 1 patient to as much as 11 patients. Although 12 articles offered information about education content, the wording and lack of detail in the description made it too difficult to accurately assign categories of education topics and to compare articles with one another. For the 17 articles that reported measures of patient knowledge, 5 of the 17 sites where the surveys were administered were located in anticoagulation clinics/centers. The number of questions ranged from as few as 4 to as many as 28, and questions were most often of multiple choice format. Three were self-administered, and 2 were completed over the telephone. Two reports described instruments along with formal testing of the validity and reliability of the instrument. Conclusion Published reports of patient education related to warfarin anticoagulation vary greatly in strategy, content, and patient testing. Prioritizing the educational domains, standardizing the educational content, and delivering the content more efficiently will be necessary to improve the quality of anticoagulation with warfarin. PMID:18275605

Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source.

PubMed

Sanna, Tommaso; Ziegler, Paul D; Crea, Filippo

2018-03-01

Cryptogenic stroke (CS) and embolic stroke of unknown source (ESUS) represent a major challenge to healthcare systems worldwide. Atrial fibrillation (AF) is commonly found after CS or ESUS. Independent of the mechanism of the index CS or ESUS, detection of AF in these patients offers the opportunity to reduce the risk of stroke recurrence by prescribing an anticoagulant instead of aspirin. The detection of AF may be pursued with different monitoring strategies. Comparison of monitoring strategies should take into account that AF detection rates reported in published studies, and then pooled in meta-analyses, are not only a function of the monitoring strategy itself, but also depend on patient-related, device-related, and study design-related factors. Once AF is found, the decision to anticoagulate a patient should be made on the basis of AF burden and the baseline risk of the patient. Empirical anticoagulation in patients with ESUS and no evidence of AF is an intriguing but still-unproven strategy and therefore should not be adopted outside of randomized clinical trials. © 2018 Wiley Periodicals, Inc.

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

PubMed

Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

2014-04-01

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral Anticoagulant Therapy

PubMed Central

Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

2012-01-01

Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

Challenges with Navigating the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation and Transfusion Management.

PubMed

Andrews, Jennifer; Winkler, Anne M

2016-10-01

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure, and there are increasingly numbers of centers worldwide performing ECLS for numerous indications. Despite the progress with advancing the technology, hemorrhagic and thrombotic complications are frequently reported and associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and an artificial circuit, anticoagulation is necessary and there is resultant activation of coagulation, fibrinolysis, as well as, an increased inflammatory response. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management while lacking expertise. From an international survey, centers often use a combination of tests, which in turn result in discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as, use of alternative anticoagulants and non-thrombogenic biomaterials. Blood transfusion during extracorporeal support typically occurs for several reasons, which includes circuit priming, restoration of oxygen carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications. As a result, the majority of patients will have been exposed to at least one blood product during extracorporeal support and transfusion utilization is high. ECLS Centers have adopted transfusion thresholds based upon practice rather than evidence as there have been no prospective studies investigating the efficacy of red cell (RBC) transfusion in patients receiving extracorporeal support. In addition, RBC transfusion has been associated with increased mortality in ECLS in several retrospective studies. Additional studies are needed to establish evidence based thresholds for transfusion support and diagnostics to guide transfusion therapy to assess efficacy of transfusion in this population, as well as, exploration of alternatives to transfusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban—an oral, direct Factor Xa inhibitor

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban. PMID:25426077

Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Niederalt, Christoph; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Tanigawa, Takahiko; Lippert, Jörg

2014-01-01

The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis.

PubMed

Marcolino, Milena Soriano; Polanczyk, Carisi Anne; Bovendorp, Ana Carolina Caixeta; Marques, Naiara Silveira; Silva, Lilian Azevedo da; Turquia, Cintia Proveti Barbosa; Ribeiro, Antonio Luiz

2016-01-01

Randomized clinical trials have shown that the new oral anticoagulants have at least similar impact regarding reduction of thromboembolic events, compared with warfarin, with similar or improved safety profiles. There is little data on real costs within clinical practice. Our aim here was to perform economic analysis on these strategies from the perspective of Brazilian society and the public healthcare system. Cost-minimization analysis; anticoagulation clinic of Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brazil. Patients at the anticoagulation clinic were recruited between August and October 2011, with minimum follow-up of four weeks. Operational and non-operational costs were calculated and corrected to 2015. This study included 633 patients (59% women) of median age 62 years (interquartile range -49-73). The mean length of follow-up was 64 ± 28 days. The average cost per patient per month was $ 54.26 (US dollars). Direct costs accounted for 32.5% of the total cost. Of these, 69.5% were related to healthcare professionals. With regards to indirect costs, 52.4% were related to absence from work and 47.6% to transportation. Apixaban, dabigatran and rivaroxaban were being sold to Brazilian public institutions, on average, for $ 49.87, $ 51.40 and $ 52.16 per patient per month, respectively, which was lower than the costs relating to warfarin treatment. In the Brazilian context, from the perspective of society and the public healthcare system, the cumulative costs per patient using warfarin with follow-up in anticoagulation clinics is currently higher than the strategy of prescribing the new oral anticoagulants.

Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

PubMed

Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

2016-12-01

Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These data will be used to better understand optimal strategies to care for these complex but increasingly common emergent real world clinical challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

Recent progress and market analysis of anticoagulant drugs

PubMed Central

Fan, Ping; Gao, Yangyang; Zheng, Minglin; Xu, Ting; Schoenhagen, Paul

2018-01-01

This review describes epidemiology of thromboembolic disease in China and abroad, evaluates trends in the development of anticoagulant drugs, and analyzes the market situation based on large amounts of accumulated data. Specifically, we describe advances in clinical application of anticoagulants and analyze the most commonly used anticoagulants in the market systematically.

Risk of gastrointestinal bleeding during anticoagulant treatment.

PubMed

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Heparin: Past, Present, and Future.

PubMed

Oduah, Eziafa I; Linhardt, Robert J; Sharfstein, Susan T

2016-07-04

Heparin, the most widely used anticoagulant drug in the world today, remains an animal-derived product with the attendant risks of adulteration and contamination. A contamination crisis in 2007-2008 increased the impetus to provide non-animal-derived sources of heparin, produced under cGMP conditions. In addition, recent studies suggest that heparin may have significant antineoplastic activity, separate and distinct from its anticoagulant activity, while other studies indicate a role for heparin in treating inflammation, infertility, and infectious disease. A variety of strategies have been proposed to produce a bioengineered heparin. In this review, we discuss several of these strategies including microbial production, mammalian cell production, and chemoenzymatic modification. We also propose strategies for creating "designer" heparins and heparan-sulfates with various biochemical and physiological properties.

Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications (Second Edition): Guidelines From the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain.

PubMed

Narouze, Samer; Benzon, Honorio T; Provenzano, David; Buvanendran, Asokumar; De Andres, José; Deer, Timothy; Rauck, Richard; Huntoon, Marc A

2018-04-01

The American Society of Regional Anesthesia and Pain Medicine (ASRA) 2012 survey of meeting attendees showed that existing ASRA anticoagulation guidelines for regional anesthesia were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors required separate guidelines for pain and spine procedures. In response, a guidelines committee was formed. After preliminary review of published complications reports and studies, the committee stratified interventional spine and pain procedures according to potential bleeding risk: low-, intermediate-, and high-risk procedures. The ASRA regional anesthesia anticoagulation guidelines were largely deemed appropriate for the low- and intermediate-risk categories, but the high-risk category required further investigation. The first guidelines specific to interventional spine and pain procedures were published in 2015. Recent reviews evaluating bleeding complications in patients undergoing specific interventional pain procedures, the development of new regional anesthesia and acute pain guidelines, and the development of new anticoagulants and antiplatelet medications necessitate complementary updated guidelines. The authors desired coordination with the authors of the recently updated regional and acute pain anticoagulation guidelines. The latest evidence was sought through extensive database search strategies and the recommendations were evidence based when available and pharmacology driven otherwise. We could not provide strength and grading of these recommendations because there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations. This publication is intended as a living document to be updated periodically with consideration of new evidence.

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

PubMed

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re-aligned oral anticoagulant therapy to the latest evidence based guidelines for stroke prophylaxis, whilst simultaneously correcting the over-utilisation of antiplatelet therapy.

Improving cost-effectiveness of and outcomes from drug therapy in patients with atrial fibrillation in managed care: role of the pharmacist.

PubMed

Johnson, Samuel G

2009-08-01

The medical care costs for procedures, medications, and testing associated with atrial fibrillation (AF) in the United States are high and projected to increase markedly in the future as the number of Americans affected grows. The burden on patient quality of life, the health care system, and society are pharmacoeconomic considerations in managing AF. To identify key pharmacoeconomic considerations in managing AF and describe ways in which managed care pharmacists can improve the cost-effectiveness of and outcomes from drug therapy for AF. The high medical care costs of AF are largely the result of the high cost of hospitalization and inpatient procedures. Recurrence of AF dramatically increases costs, especially for hospital care. Managed care pharmacists have many opportunities to provide cost-effective care to and improve outcomes in patients with AF. Policy and process review, population management, and case management are key strategies for improving outcomes in patients with AF. Pharmacist input into policy and process review, including pharmacy benefits design, formulary management, and the use of information technology, can help ensure that the use of drug therapy for AF is cost-effective. Population management strategies, such as development of clinical pathways and patient registries, seek to improve the quality, consistency, and cost-effectiveness of care and the likelihood that desired therapeutic outcomes are achieved through targeted interventions. Case management strategies focus on longitudinal care for individuals in order to improve quality. Pharmacist-managed anticoagulation services and antiarrhythmic drug monitoring are the 2 most widely known case management strategies for patients with AF. Managed care pharmacists can screen patients with AF for the use of anticoagulation, which is needed to prevent embolic stroke but is under-used, even though recommended by evidence-based guidelines. The clinical efficacy and cost-effectiveness of pharmacist-managed anticoagulation services for patients with AF are well documented. Pharmacist-managed antiarrhythmic drug monitoring is a less well-known case management strategy that facilitates early detection and intervention to minimize toxicity. Managed care pharmacists can play an instrumental role in implementing strategies to improve the cost-effectiveness of and outcomes from drug therapy for AF.

Early Transcatheter Aortic Valve Function With and Without Therapeutic Anticoagulation.

PubMed

Hiremath, Pranoti G; Kearney, Kathleen; Smith, Bryn; Don, Creighton; Dvir, Danny; Aldea, Gabriel; Reisman, Mark; McCabe, James M

2017-11-01

Prosthetic leaflet thrombosis is a growing concern in transcatheter aortic valve replacement (TAVR). Given the uncertainty of best practices for antiplatelet and anticoagulation therapies in the post-TAVR period, additional evidence regarding the impact of anticoagulation on prosthetic valve function after TAVR is needed. Patients undergoing native-valve TAVR at a single academic institution between 2012 and 2015 were analyzed based on any anticoagulant use at hospital discharge post TAVR. Changes in prosthetic valve peak velocity and mean gradient were assessed based on transthoracic echocardiograms performed immediately following valve implant and at 4-week follow-up. Multivariate regression analyses were performed to explore the impact of anticoagulation status on early TAVR valve performance. For 403 patients, there were no available data to analyze. Of those, 29.6% were discharged on anticoagulation. Following TAVR, the average mean prosthetic valve gradient was 11.8 ± 5.6 mm Hg and peak velocity was 2.33 ± 0.52 m/s. There were no significant differences between anticoagulated and non-anticoagulated groups in the mean or peak gradients or velocity immediately following implant or at 4 weeks, which remained true following multivariate adjustment (P=.80 for delta mean gradient; P=.91 for delta peak velocity). Our data suggest that the absence of anticoagulation is not associated with short-term degradation in TAVR performance and do not support the routine use of anticoagulation following native-valve TAVR.

Therapeutic implications of transesophageal echocardiography after transthoracic echocardiography on acute stroke patients

PubMed Central

de Abreu, Tiago Tribolet; Mateus, Sonia; Carreteiro, Cecilia; Correia, Jose

2008-01-01

Background The role of transesophageal echocardiography (TEE) in the evaluation of acute stroke patients is still ill-defined. We conducted a prospective observational study to find the prevalence of TEE findings that indicate anticoagulation as beneficial, in acute ischemic stroke patients without indication for anticoagulation based on clinical, electrocardiographic and transthoracic echocardiography (TTE) findings. Methods We prospectively studied all patients referred to our laboratory for TTE and TEE. Patients were excluded if the diagnosis was not acute ischemic stroke or if they had an indication for anticoagulation based on clinical, electrocardiographic, or TTE data. Patients with TEE findings that might indicate anticoagulation as beneficial were identified. Results A total of 84 patients with acute ischemic stroke and without indication for anticoagulation based on clinical and electrocardiographic or TTE data were included in the study. Findings indicating anticoagulation as beneficial were found in 32.1%: spontaneous echo contrast (1.2%), complex aortic atheroma (27.4%), thrombus (8.3%), and simultaneous patent foramen ovale and atrial septal aneurysm (2.4%). Conclusions The results of our study show that TEE can have therapy implications in 32.1% of ischemic stroke patients in sinus rhythm and with TTE with no indication for anticoagulation. PMID:18629351

Variations in Anticoagulation Practices Following the Maze Procedure.

PubMed

Chung, Jennifer; Sami, Magdi; Albert, Carole; Varennes, Benoit De

2015-01-01

The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

PubMed

Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

2013-05-01

To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Risk-adapted management of pulmonary embolism.

PubMed

Barco, Stefano; Konstantinides, Stavros V

2017-03-01

The presence and severity of right ventricular (RV) dysfunction is a key determinant of prognosis in the acute phase of pulmonary embolism (PE). Risk-adapted treatment strategies continue to evolve, tailoring initial management to the clinical presentation and the functional status of the RV. Beyond pharmacological and, if necessary, mechanical circulatory support, systemic thrombolysis remains the mainstay of treatment for hemodynamically unstable patients; in contrast, it is not routinely recommended for intermediate-risk PE. Catheter-directed pharmacomechanical reperfusion treatment represents a promising option for minimizing bleeding risk; for reduced-dose intravenous thrombolysis, the data are still preliminary. Non-vitamin K-dependent oral anticoagulants, directly inhibiting factor Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran), have simplified initial and long-term anticoagulation for PE while reducing major bleeding risk. Use of vena cava filters should be restricted to selected patients with absolute contraindications to anticoagulation, or PE recurrence despite adequately dosed anticoagulants. © 2017 Elsevier Ltd. All rights reserved.

Comparative effectiveness analysis of anticoagulant strategies in a large observational database of percutaneous coronary interventions.

PubMed

Wise, Gregory R; Schwartz, Brian P; Dittoe, Nathaniel; Safar, Ammar; Sherman, Steven; Bowdy, Bruce; Hahn, Harvey S

2012-06-01

Percutaneous coronary intervention (PCI) is the most commonly used procedure for coronary revascularization. There are multiple adjuvant anticoagulation strategies available. In this era of cost containment, we performed a comparative effectiveness analysis of clinical outcomes and cost of the major anticoagulant strategies across all types of PCI procedures in a large observational database. A retrospective, comparative effectiveness analysis of the Premier observational database was conducted to determine the impact of anticoagulant treatment on outcomes. Multiple linear regression and logistic regression models were used to assess the association of initial antithrombotic treatment with outcomes while controlling for other factors. A total of 458,448 inpatient PCI procedures with known antithrombotic regimen from 299 hospitals between January 1, 2004 and March 31, 2008 were identified. Compared to patients treated with heparin plus glycoprotein IIb/IIIa inhibitor (GPI), bivalirudin was associated with a 41% relative risk reduction (RRR) for inpatient mortality, a 44% RRR for clinically apparent bleeding, and a 37% RRR for any transfusion. Furthermore, treatment with bivalirudin alone resulted in a cost savings of $976 per case. Similar results were seen between bivalirudin and heparin in all end-points. Combined use of both bivalirudin and GPI substantially attenuated the cost benefits demonstrated with bivalirudin alone. Bivalirudin use was associated with both improved clinical outcomes and decreased hospital costs in this large "real-world" database. To our knowledge, this study is the first to demonstrate the ideal comparative effectiveness end-point of both improved clinical outcomes with decreased costs in PCI. ©2012, Wiley Periodicals, Inc.

Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

PubMed

Black-Maier, Eric; Kim, Sunghee; Steinberg, Benjamin A; Fonarow, Gregg C; Freeman, James V; Kowey, Peter R; Ansell, Jack; Gersh, Bernard J; Mahaffey, Kenneth W; Naccarelli, Gerald; Hylek, Elaine M; Go, Alan S; Peterson, Eric D; Piccini, Jonathan P

2017-09-01

Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized. Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation. Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status. Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent. Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients. © 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

PubMed

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade

PubMed Central

Atar, Dan; Bode, Christoph; Stuerzenbecher, André; Verheugt, Freek W A

2014-01-01

The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acute MI over the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of further ACS events, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post-ACS thrombosis and limitations of current therapeutic approaches. The recent approval in Europe of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acute MI and discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting. PMID:24494730

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address themore » strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.« less

Argatroban for an alternative anticoagulant in HIT during ECMO.

PubMed

Rougé, Alain; Pelen, Felix; Durand, Michel; Schwebel, Carole

2017-01-01

Extracorporeal membrane oxygenation (ECMO) have become more frequently used in daily ICU practice, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication while on extracorporeal membrane oxygenation (ECMO). HIT confirmation directly impacts on anticoagulant strategy requiring no delay unfractionated heparin discontinuation to be replaced by alternative systemic anticoagulant treatment. We report two clinical cases of HIT occurring during ECMO in various settings with subsequent recovery with argatroban and provide literature review to help physicians treat HIT during ECMO in clinical daily practice. HIT during ECMO is uncommon, and despite the absence of recommendation, argatroban seems to be an appropriate and safe therapeutic option. Finally, there are not enough arguments favouring routine circuit change in the event of HIT during ECMO.

The mythology of anticoagulation therapy interruption for dental surgery.

PubMed

Wahl, Michael J

2018-01-01

Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Splanchnic Vein Thrombosis in the Myeloproliferative Neoplasms.

PubMed

Akpan, Imo J; Stein, Brady Lee

2018-06-01

To review the epidemiology, diagnostic challenges, pathogenesis, and treatment strategies for patients with myeloproliferative neoplasm-associated splanchnic vein thrombosis. The epidemiology of myeloproliferative neoplasm-associated splanchnic vein thrombosis (MPN-SVT) has been well characterized. While typical MPN-associated thrombosis affects older patients and involves the arterial circulation, MPN-SVT mostly impacts younger women. An association with JAK2 V617F is well-known; recent studies have demonstrated only a weak association with CALR mutations. JAK inhibition may represent a novel treatment strategy, complementing anticoagulation, and management of portal hypertension. While the epidemiology has been well characterized, more work is needed to identify novel contributors to disease pathogenesis, beyond the JAK2 V617F mutation itself, and endothelial compromise. Testing for MPN mutations in the setting of non-cirrhotic SVT is commonplace; JAK2 V617F is the most likely to be identified. Testing for CALR or MPL mutations requires clinical judgement, though not unreasonable. The mainstay of therapy is indefinite anticoagulation; the role of direct oral anticoagulants is unclear. JAK inhibition may play a role in addressing associated splenomegaly and portal hypertension.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

PubMed

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

Internal Medicine Physicians’ Perceptions Regarding Rate versus Rhythm Control for Atrial Fibrillation

PubMed Central

McCabe, James M.; Johnson, Colleen J; Marcus, Gregory M

2011-01-01

Atrial fibrillation (AF) is often managed by general internal medicine physicians. Available data suggest that guidelines regarding AF management are often not followed, but the reasons for this remain unknown. We sought to assess the knowledge and beliefs of internists regarding strategies to treat AF. We conducted a national electronic survey of internal medicine physicians regarding their perceptions of optimal AF management, with an emphasis on the rationale for choosing a rhythm or rate control strategy. One hundred and forty-eight physicians from 36 different states responded (representing at least 19% of unique e-mails opened). Half of the respondents reported managing their AF patients independently without referral to a cardiologist. Seventy-three percent of participants believe a rhythm control strategy conveys a decreased stroke risk, 64% believe there is a mortality benefit to rhythm control, and 55% think that it would help avoid long term anticoagulation. Comparing those who prefer a rhythm control strategy to everyone else, those who favor rhythm control statistically significantly more often believe that rhythm control reduces the risk for stroke (96% versus 67%, p=0.009) and that rhythm control allows for the discontinuation of anticoagulation therapy (76% versus 49%, p=0.045). In conclusion, contrary to available data in clinical trials and recent guidelines regarding the rationale for choosing a rhythm control strategy in treating AF, the majority of study participants believe that rhythm control decreases stroke risk, decreases mortality, and allows for discontinuation of anticoagulation therapy. These prevalent misconceptions may substantially contribute to guideline non-adherence. PMID:19195516

Management Strategies for Vitamin K Antagonists Reversal in Patients With Major Bleeding: A Survey of Italian Emergency Departments.

PubMed

Bernardi, Enrico; Imberti, Davide; Ferrari, Annamaria

2017-01-01

Emergency physicians frequently deal with patients on vitamin K antagonists (VKAs) suffering major bleeding events, and rapid reversal of anticoagulation in this setting is of paramount importance. In Italy, given the absence of specific national guidelines, local policies are likely to differ, possibly impacting on clinical outcomes. We decided to perform a telephone survey among Italian emergency physicians to evaluate management strategies for VKAs reversal in patients with major bleeding. We conducted a computer-assisted, 10-minute telephone survey of 15 questions, focusing on the local prevalence, assessment, and management strategies of major and intracranial hemorrhage (ICH) occurring in patients on VKAs. We planned to interview a sample of 320 Italian emergency physicians. Institutions from all geographic areas of Italy were to participate in the survey. Of the 320 physicians contacted, 150 (47%) completed the survey, 95% being employed in public hospitals. Focusing on ICH, only 29% of the responders stated they would reverse anticoagulation irrespective of the international normalized ratio value, and only 27% would use prothrombin-complex concentrate as first-line agent. In patients needing urgent neurosurgical operation, less than 50% would administer prothrombin-complex concentrate before surgery. The average knowledge of management strategies for reversal of anticoagulation displayed by Italian emergency physicians appears to be unsatisfactory. The need for an extensive educational program and for the implementation of specific guidelines, possibly endorsed by Scientific Societies, cannot be underemphasized. © The Author(s) 2015.

Anticoagulants for secondary prevention after acute myocardial infarction: lessons from the past decade.

PubMed

Atar, Dan; Bode, Christoph; Stuerzenbecher, André; Verheugt, Freek W A

2014-08-01

The impact of an acute coronary syndrome (ACS) event, such as an acute myocardial infarction (MI), is not limited to the acute management phase; patients face an elevated risk of residual atherothrombotic events that commonly requires chronic management for months or even years. Significant advances have been made in both the acute and chronic management of patients with acute MI over the past decade, resulting in improved prognoses. One of the hallmarks of modern treatment strategies is more aggressive antiplatelet treatment regimens. However, the risks of further ACS events, stroke and premature death remain elevated in these patients, and addressing this residual risk is challenging owing to interpatient variability, differences in management strategies between centres and countries, incomplete understanding of the specific pathophysiology of post-ACS thrombosis and limitations of current therapeutic approaches. The recent approval in Europe of the direct oral anticoagulant rivaroxaban for use in this setting in combination with clopidogrel and acetylsalicylic acid offers another strategy to consider in the management of these patients, and clinical strategies in this area continue to evolve. In this review, we chart the progress made over the past decade in reducing the burden of secondary thromboembolic events after acute MI and discuss the current position of and future perspectives on the inclusion of oral anticoagulants into care pathways in this setting. © 2014 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

Efficacy of vitamin E-bonded polysulfone dialyzer and polysulfone dialyzer on a series of non-anticoagulant hemodialysis.

PubMed

Torato, Toshihiro; Doi, Kent; Negishi, Kousuke; Hamasaki, Yoshifumi; Satonaka, Hiroshi; Hanafusa, Norio; Noiri, Eisei

2013-01-01

Non-anticoagulant hemodialysis is conducted occasionally at limited numbers of hospitals on an empirical basis. This study examines the efficacy of polysulfone and vitamin E-bonded polysulfone dialyzer for non-anticoagulant hemodialysis. These dialyzers were assigned one after the other for a vintage hemodialysis patient complicated with uncontrollable bleeding. The patient's vital and console data throughout non-anticoagulant hemodialysis were monitored serially. Both dialyzers were reasonably applicable to hemodialysis without major clotting. The scheduled treatment period was completed. Vitamin E-bonded polysulfone dialyzer was superior to non-anticoagulant hemodialysis based on venous pressure observed during treatment.

Study protocol for the dabigatran, apixaban, rivaroxaban, edoxaban, warfarin comparative effectiveness research study.

PubMed

Krumme, Alexis A; Pawar, Ajinkya; Schneeweiss, Sebastian; Glynn, Robert J; Choudhry, Niteesh K; Kulldorff, Martin; Ortiz, Adrian Santiago; Avorn, Jerome; Gagne, Joshua J

2018-01-01

Since 2010, four oral anticoagulants have been approved for marketing in addition to warfarin for treatment of thromboembolic disease. Limited head-to-head data exist comparing these treatments, leaving patients and clinicians with little guidance for selecting a strategy that balances recurrence reduction with bleeding risk. In the dabigatran, apixaban, rivaroxban, edoxaban and warfarin comparative effectiveness research study, we compare all five currently available oral anticoagulant agents for the extended treatment of deep venous thrombosis and pulmonary embolism, as well as no extended treatment, and evaluate whether results differ in specific sub-populations. As our population includes Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, our results will likely be transportable to the majority of US patients experiencing a DVT or pulmonary embolism. NCT03271450.

Sustained impact of anticoagulant control achieved in an anticoagulation management service after transfer of management to the primary care physician.

PubMed

Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T

2012-02-01

To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant management by the AMS relative to PCP care (p=0.01), and given the choice, patients preferred AMS care (p=0.001). During this 6-month trial, anticoagulation control did not significantly differ between patients who continued to receive anticoagulation management by the AMS and those who transferred to their PCP for anticoagulation management, indicating that the effects of AMS care were sustained. Although patients were more satisfied and preferred to stay with AMS care, this study shows that select patients could have their anticoagulation care transferred to their PCP without compromising anticoagulation control. © 2012 Pharmacotherapy Publications, Inc.

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

PubMed

Singer, Adam J; Quinn, Adam; Dasgupta, Neil; Thode, Henry C

2017-01-01

Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin. Copyright © 2016 Elsevier Inc. All rights reserved.

Stroke prevention with oral anticoagulation in older people with atrial fibrillation - a pragmatic approach.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-08-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.

Stroke Prevention with Oral Anticoagulation in Older People with Atrial Fibrillation - A Pragmatic Approach

PubMed Central

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-01-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715

[Oral anticogulation for non-valvular atrial fibrilation in the elderly].

PubMed

Veiga Fernández, Fernando; Malfeito Jiménez, María del Rocío; Barros Cerviño, Sonia María; Magariños Losada, María del Mar

2015-01-01

Anticoagulation in elderly people with non-valvular atrial afibrillation (AF) is a challenge, due to the thromboembolic, as well as the haemorrhagic risks. The correct use of anticoagulants in these patients has shown a higher net clinical benefit when comparing it with a younger population. Non-vitamin K antagonist oral anticoagulants (NOACs) have been compared to oral vitamin K antagonists in several studies that included a sufficient number of elderly people. Favourable results for non-vitamin K antagonist oral anticoagulants were obtained in these studies, making them the preferred treatment for this group of patients. Basing the estimations on indirect comparisons, the ideal anticoagulant and the specific dose for each particular case has been determined. Finally, a new algorithm has been developed that relates these parameters. Geriatric assessment is the key to the indication for an anticoagulation, the type of anticoagulant needed, and also the best way to optimise all the factors for a safe anticoagulation. The arrival of non-vitamin K antagonist oral anticoagulants will enhance the efficient thromboembolic prophylaxis rate in elderly people with AF. This new treatment will remove different controversial prophylaxis, such as antiaggregants. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

International normalized ratio self-testing and self-management: improving patient outcomes.

PubMed

Pozzi, Matteo; Mitchell, Julia; Henaine, Anna Maria; Hanna, Najib; Safi, Ola; Henaine, Roland

2016-01-01

Long term oral anti-coagulation with vitamin K antagonists is a risk factor of hemorrhagic or thromebomlic complications. Periodic laboratory testing of international normalized ratio (INR) and a subsequent dose adjustment are therefore mandatory. The use of home testing devices to measure INR has been suggested as a potential way to improve the comfort and compliance of the patients and their families, the frequency of monitoring and, finally, the management and safety of long-term oral anticoagulation. In pediatric patients, increased doses to obtain and maintain the therapeutic target INR, more frequent adjustments and INR testing, multiple medication, inconstant nutritional intake, difficult venepunctures, and the need to go to the laboratory for testing (interruption of school and parents' work attendance) highlight those difficulties. After reviewing the most relevant published studies of self-testing and self-management of INR for adult patients and children on oral anticoagulation, it seems that these are valuable and effective strategies of INR control. Despite an unclear relationship between INR control and clinical effects, these self-strategies provide a better control of the anticoagulant effect, improve patients and their family quality of life, and are an appealing solution in term of cost-effectiveness. Structured education and knowledge evaluation by trained health care professionals is required for children, to be able to adjust their dose treatment safely and accurately. However, further data are necessary in order to best define those patients who might better benefit from this multidisciplinary approach.

Anticoagulation by factor Xa inhibitors.

PubMed

Orfeo, T; Butenas, S; Brummel-Ziedins, K E; Gissel, M; Mann, K G

2010-08-01

Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach. To assess anticoagulant strategies targeting FXa. A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of FXa-directed anticoagulants [an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban] in experimental regimens relevant to long-term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Computational representations of each anticoagulant's efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long-term and acute clinical applications, respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an FXa inhibitor. We have reported that FIXa contributes to the long-term capacity of clot-associated catalysts to restart a coagulation process, suggesting that the enhanced anti-FIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. © 2010 International Society on Thrombosis and Haemostasis.

STS/SCA/AmSECT Clinical Practice Guidelines: Anticoagulation during Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John

2018-03-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, the Society of Thoracic Surgeons (STS), the Society of Cardiovascular Anesthesiologists (SCA), and the American Society of Extracorporeal Technology (AmSECT) developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered together to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation for CPB using the available evidence. To identify relevant evidence a systematic review was outlined and literature searches were conducted in PubMed® using standardized MeSH terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published prior to 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the AHA/ACCF Task Force on Practice Guidelines. Recommendations were written in the three following areas 1) Heparin dosing and monitoring for initiation and maintenance of CPB, 2) Heparin contraindications and heparin alternatives, 3) Reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and expand upon the evidence base on the topic of anticoagulation for CPB.

Causes of Death in Patients with Venous Thromboembolism Anticoagulated with Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

PubMed

Gómez-Outes, Antonio; Terleira-Fernández, Ana Isabel; Lecumberri, Ramón; Suárez-Gea, Mª Luisa; Calvo-Rojas, Gonzalo; Vargas-Castrillón, Emilio

2018-06-01

Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3-4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2-25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A pharmacoeconomic study of traditional anticoagulation versus direct oral anticoagulation for the treatment of venous thromboembolism in the emergency department.

PubMed

Law, Stephanie; Ghag, Daljit; Grafstein, Eric; Stenstrom, Robert; Harris, Devin

2016-09-01

Patients with venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) are commonly treated as outpatients. Traditionally, patients are anticoagulated with low-molecular-weight heparin (LMWH) and warfarin, resulting in return visits to the ED. The direct oral anticoagulant (DOAC) medications do not require therapeutic monitoring or repeat visits; however, they are more expensive. This study compared health costs, from the hospital and patient perspectives, between traditional versus DOAC therapy. A chart review of VTE cases at two tertiary, urban hospitals from January 1, 2010 to December 31, 2012 was performed to capture historical practice in VTE management, using LMWH/warfarin. This historical data were compared against data derived from clinical trials, where a DOAC was used. Cost minimization analyses comparing the two modes of anticoagulation were completed from hospital and patient perspectives. Of the 207 cases in the cohort, only 130 (63.2%) were therapeutically anticoagulated (international normalized ratio 2.0-3.0) at emergency department (ED) discharge; patients returned for a mean of 7.18 (range: 1-21) visits. Twenty-one (10%) were admitted to the hospital; 4 (1.9%) were related to VTE or anticoagulation complications. From a hospital perspective, a DOAC (in this case, rivaroxaban) had a total cost avoidance of $1,488.04 per VTE event, per patient. From a patient perspective, it would cost an additional $204.10 to $349.04 over 6 months, assuming no reimbursement. VTE management in the ED has opportunities for improvement. A DOAC is a viable and cost-effective strategy for VTE treatment from a hospital perspective and, depending on patient characteristics and values, may also be an appropriate and cost-effective option from a patient perspective.

The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

PubMed

Ten Cate, V; Ten Cate, H; Verheugt, F W A

2016-10-01

There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients.

Switching, Adverse Effects and Use of Over-the-Counter Analgesics among Users of Oral Anticoagulants: A Pharmacy-based Survey.

PubMed

Hellfritzsch, Maja; Hyllested, Lea Maria Rønneberg; Meegaard, Line; Wiberg-Hansen, Alexander; Grove, Erik Lerkevang; Pottegård, Anton

2017-07-01

Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We collected information concerning the patients' knowledge of their anticoagulant treatment including prior drug switching. Further, patients were asked about use of over-the-counter analgesics, adverse effects and how the treatment affected their everyday life. Among 335 eligible patients, 301 (90%) agreed to participate. Atrial fibrillation was the most common indication (65%), and most patients filled a prescription for a non-vitamin K antagonist oral anticoagulant (NOAC) (58%). Among the 12% (n = 35) of participants who had switched oral anticoagulant treatment, 69% had switched from a vitamin K antagonist (VKA) to a NOAC. Switching was most frequently caused by inconvenience (34%) and adverse effects (23%). Although half of all patients had recently bought over-the-counter analgesics, purchase of ibuprofen and aspirin was rare (6%). More VKA users than NOAC users felt limited in their everyday life because of anticoagulant treatment (18% versus 9%). Among non-incident NOAC users, 21% had experienced adverse effects during their current treatment. Based on first-hand information from a large sample of anticoagulant users, we conclude that the main drug-related issues leading to anticoagulant switching and perceived limitations in everyday life were inconvenience and adverse effects. This varied between drug groups. Further, use of NSAIDs obtained over the counter was rare. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

How are patients with atrial fibrillation approached and informed about their risk profile and available therapies in Europe? Results of the European Heart Rhythm Association Survey.

PubMed

Potpara, Tatjana S; Pison, Laurent; Larsen, Torben B; Estner, Heidi; Madrid, Antonio; Blomström-Lundqvist, Carina

2015-03-01

This European Heart Rhythm (EHRA) Scientific Initiatives Committee EP Wire Survey aimed at exploring the common practices in approaching patients with atrial fibrillation (AF) and informing them about their risk profiles and available therapies in Europe. In the majority of 53 responding centres, patients were seen by cardiologists (86.8%) or arrhythmologists (64.2%). First- and follow-up visits most commonly lasted 21-30 and 11-20 min (41.5 and 69.8% of centres, respectively). In most centres (80.2%) stroke and bleeding risk had the highest priority for discussion with AF patients; 50.9% of centres had a structured patient education programme for stroke prevention. Individual patient stroke risk was assessed at every visit in 69.2% of the centres; 46.1% of centres had a hospital-based anticoagulation clinic. Information about non-vitamin K oral anticoagulants (NOACs) was communicated to all AF patients eligible for oral anticoagulation (38.5% of centres) or to warfarin-naive/unstable patients (42.3%). Only two centres (3.8%) had a structured NOAC adherence follow-up programme; in eight centres (15.4%) patients were requested to sign the statement they have been informed about the risks of non-adherence to NOAC therapy, and three centres (5.8%) had a patient education programme. Patient preferences were of the highest relevance regarding oral anticoagulation and AF ablation (64.7 and 49.0% of centres, respectively). This EP Wire Survey shows that in Europe considerable amount of time and resources are used in daily clinical practice to inform AF patients about their risk profile and available therapies. However, a diversity of strategies used across the European hospitals was noted, and further research is needed to better define optimal strategies for informing AF patients about their risk profile and treatment options. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.

PubMed

Peacock, W Frank

2014-10-01

The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity as part of the inpatient workup if time allows, and the potential use of hemodialysis, prohemostatic agents, and reversal agents when available.

Management of recent-onset sustained atrial fibrillation: pharmacologic and nonpharmacologic strategies.

PubMed

Lau, Dennis H; Kalman, Jonathan; Sanders, Prashanthan

2014-09-01

Recent studies have highlighted significant variations in the management of recent-onset sustained atrial fibrillation (AF). We aim to provide a succinct and clear management algorithm for physicians treating patients with recent-onset sustained AF. We performed a comprehensive search of the literature on the management of recent-onset sustained AF with focus on studies reporting cardioversion of AF, antiarrhythmic agents, and anticoagulation. We also reviewed recent practice guidelines on AF management. This review provides a guide on a tailored management approach of patients with recent-onset sustained AF. After initial detailed clinical assessment, optimal rate and rhythm control options can be provided, depending on hemodynamic stability, duration of AF episode, and AF stroke risk. Issues surrounding electrical and pharmacologic cardioversion are discussed in detail. We emphasize the importance of thromboembolic risk assessment and appropriate anticoagulation surrounding the point of cardioversion. Last, we highlighted the need for appropriate specialized follow-up care after acute AF management. Despite the highly heterogeneous clinical presentations, management of recent-onset sustained AF must include stroke risk assessment, appropriate anticoagulation, and follow-up care in all patients beyond optimum rate and rhythm control strategies. Copyright © 2014. Published by Elsevier Inc.

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

PubMed

Shatzel, J J; Olson, S R; Tao, D L; McCarty, O J T; Danilov, A V; DeLoughery, T G

2017-05-01

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib. © 2017 International Society on Thrombosis and Haemostasis.

New strategies for the treatment of acute venous thromboembolism.

PubMed

Prandoni, Paolo; Lensing, Anthonie W A; Pesavento, Raffaele

2006-11-01

In recent years, new opportunities have emerged that have the potential to change rapidly the therapeutic scenario of patients with acute venous thromboembolism (VTE). Selected patients with deep vein thrombosis (DVT) can be treated effectively and safely at home with fixed doses of low molecular weight heparins. The prompt administration of compression elastic stockings in addition to anticoagulant drugs in patients with acute DVT has the potential to halve the rate of late postthrombotic sequelae. The long-term use of low molecular weight heparins is likely to be more effective than oral anticoagulants for the secondary prevention of VTE in patients with advanced malignancy. Patients with pulmonary embolism and right ventricular dysfunction might benefit from the early administration of thrombolytic drugs in combination with heparin to a greater extent than from heparin alone. Despite an impressive amount of clinical information on the proper duration of oral anticoagulants in patients with unprovoked VTE, the optimal long-term treatment of these patients remains undefined. Finally, new categories of drugs are emerging that have the potential to replace conventional anticoagulants in the near future. They include compounds that inhibit factor Xa or thrombin.

Percutaneous Occlusion of the Left Atrial Appendage with the Watchman Device in an Active Duty Sailor with Atrial Fibrillation and Recurrent Thromboembolism Despite Appropriate Use of Oral Anticoagulation.

PubMed

Cox, Justin M; Choi, Anthony J; Oakley, Luke S; Francisco, Gregory M; Nayak, Keshav R

2018-05-23

Atrial fibrillation is the most common significant cardiac arrhythmia and is associated with a five-fold increased risk of stroke from thromboembolism. Over 94% of these emboli arise from the left atrial appendage. Systemic embolic phenomena are rare, accounting for less than 1 out of 10 of all embolic events, but have a similar prevention strategy. Anticoagulation significantly reduces the risk of these events, and thus forms the cornerstone of therapy for most patients with atrial fibrillation. Left atrial appendage occlusion with the Watchman device is a recently approved alternative for stroke prevention in selected patients. We present a case of an active duty U.S. Navy sailor at low risk for thromboembolism who nonetheless suffered recurrent thromboembolic events despite appropriate anticoagulation, and thus underwent Watchman implantation. The therapy in this case will ideally provide a lifetime of protection from recurrent systemic embolization while allowing the patient to continue his active duty military career without restriction due to oral anticoagulation.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

PubMed Central

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-01

ABSTRACT Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R1 and R2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect. PMID:27759485

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

PubMed

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-02

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke.

PubMed

Lightowlers, S; McGuire, A

1998-09-01

A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

Estimated effect of an integrated approach to suspected deep venous thrombosis using limited-compression ultrasound.

PubMed

Poley, Rachel A; Newbigging, Joseph L; Sivilotti, Marco L A

2014-09-01

Deep vein thrombosis (DVT) is both common and serious, yet the desire to never miss the diagnosis, coupled with the low specificity of D-dimer testing, results in high imaging rates, return visits, and empirical anticoagulation. The objective of this study was to evaluate a new approach incorporating bedside limited-compression ultrasound (LC US) by emergency physicians (EPs) into the workup strategy for DVT. This was a cross-sectional observational study of emergency department (ED) patients with suspected DVT. Patients on anticoagulants; those with chronic DVT, leg cast, or amputation; or when the results of comprehensive imaging were already known were excluded. All patients were treated in the usual fashion based on the protocol in use at the center, including comprehensive imaging based on the modified Wells score and serum D-dimer testing. Seventeen physicians were trained and performed LC US in all subjects. The authors identified a priori an alternate workup strategy in which DVT would be ruled out in "DVT unlikely" (Wells score < 2) patients if the LC US was negative and in "DVT likely" (Wells score ≥ 2) patients if both the LC US and the D-dimer were negative. The criterion standard was based on comprehensive imaging interpreted by radiologists blinded to LC US findings and by structured medical record review at 6 months in patients without comprehensive imaging. A total of 227 patients were enrolled (47% DVT likely), of whom 24 had DVT. The LC US was positive in 27 cases (21 actually DVT positive), indeterminate in 28 (one DVT positive), and negative in 172 (two DVT positive). Of 130 patients deemed DVT negative by the new strategy, one had confirmed DVT (miss rate = 0.8%; 95% confidence interval [CI] = 0.1% to 4.0%), but this patient had been misclassified by the treating physician as low risk by Wells criteria. The stand-alone sensitivity and specificity of LC US were 91% (95% CI = 70% to 98%) and 97% (95% CI = 92% to 99%), respectively. Incorporating LC US into the diagnostic approach would have reduced the rate of comprehensive imaging from 70% to 43%, D-dimer testing from 100% to 33%, and the mean time to diagnostic certainty by 5.0 hours and avoided 24 (11%) return visits for imaging and 10 (4.4%) cases of unnecessary anticoagulation. In 19% of cases, the treating and scanning physician disagreed whether the patient was DVT likely or DVT unlikely based on Wells score (κ = 0.62; 95% CI = 0.48 to 0.77). Limited-compression US holds promise as one component of the diagnostic approach to DVT, but should not be used as a stand-alone test due to imperfect sensitivity. Tradeoffs in diagnostic efficiency for the sake of perfect sensitivity remain a difficult issue collectively in emergency medicine (EM), but need to be scrutinized carefully in light of the costs of overinvestigation, delays in diagnosis, and risks of empirical anticoagulation. © 2014 by the Society for Academic Emergency Medicine.

Design of anticoagulant surfaces based on cellulose nanocrystals.

PubMed

Ehmann, Heike M A; Mohan, Tamilselvan; Koshanskaya, Maria; Scheicher, Sylvia; Breitwieser, Doris; Ribitsch, Volker; Stana-Kleinschek, Karin; Spirk, Stefan

2014-11-07

The anticoagulant activity of surfaces decorated with cellulose nanocrystals (CNCs) prepared via sulfuric acid hydrolysis, is explored. Such surfaces bear a high amount of negatively charged sulfate groups, which mimic the naturally occurring anticoagulant heparin in terms of charge density. It is demonstrated that CNC decorated surfaces significantly enhance the coagulation times of blood plasma and whole blood as proven by QCM-D and simple clotting tests.

Emerging therapeutic uses of direct-acting oral anticoagulants: An evidence-based perspective.

PubMed

Raschi, Emanuel; Bianchin, Matteo; De Ponti, Roberto; De Ponti, Fabrizio; Ageno, Walter

2017-06-01

Direct-acting oral anticoagulants (DOACs) were claimed to cause a potential paradigm shift in the therapeutic scenario of patients requiring short- and long-term anticoagulation, by virtue of their pharmacological properties, perceived as innovative. The evidence gathered so far (from pre-approval pivotal trials to real-world post-marketing observational data) consistently confirmed that DOACs are overall comparable to vitamin-K antagonists (VKAs) in terms of safety, efficacy and effectiveness and unequivocally documented a consistent and clinically relevant reduced risk of intracranial bleeding in the settings of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE). Interestingly, two parallel paths can be identified in the current research scenario: A) in the aforementioned consolidated therapeutic indications, an innovative approach is directed towards tailored treatment strategies, to identify patients most likely to benefit from one of the different anticoagulant drugs, in particular subpopulations at increased risk of adverse events (e.g., bleeding); B) in unconventional settings, DOACs are gaining interest for potential use in emerging diseases characterized by arterial and venous thromboembolic risk. In these scenarios, the risk-benefit profile of DOACs, as compared to VKAs or heparins, is less defined. The aim of this review is to critically assess the body of evidence underlying emerging therapeutic uses of DOACs (e.g., heparin-induced thrombocytopenia, anti-phospholipid antibody syndrome), including evolving issues in special populations (e.g., patients with VTE and cancer or cirrhosis). This will be achieved by analyzing the strength (i.e., systematic reviews, randomized clinical trials, observational studies, case report/series) and consistency (i.e., concordance) of both published and unpublished evidence registered in major public repositories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spontaneous Rectus Sheath Hematoma: an Overview of 4-Year Single Center Experience.

PubMed

Aktürk, Okan Murat; Kayılıoğlu, Selami Ilgaz; Aydoğan, İhsan; Dinç, Tolga; Yildiz, Baris; Cete, Mükerrem; Erdoğan, Ahmet; Coşkun, Faruk

2015-12-01

Rectus sheath hematoma is a clinical entity characterized by the presence of blood within rectus abdominis muscle sheath. The aim of this study was to analyze clinical characteristics, diagnostic approach, treatment strategy, and outcomes of patients with rectus sheath hematoma. Patients diagnosed and treated for spontaneous rectus sheath hematoma between March 2010 and March 2014 were included in the study. A total of 10 patients were diagnosed as spontaneous rectus sheath hematoma. The mean age was 66.5 ± 16.9 years, and the mean hospital stay was 4.4 ± 1.8 days. There was no mortality. Six patients were using anticoagulant or antiplatelet agents. Eight patients recovered after conservative treatment. Two patients underwent surgery. Spontaneous rectus sheath hematoma is associated with anticoagulant therapy. Cases with abdominal pain and a non-pulsatile abdominal mass particularly in elderly women should be kept in mind. Treatment is mostly based on supportive care to preserve hemodynamic stability.

Coagulation Management in Jersey Calves: An ex vivo Study.

PubMed

Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

2017-01-01

Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

Evaluation of the safety and efficacy of an edoxaban-based antithrombotic regimen in patients with atrial fibrillation following successful percutaneous coronary intervention (PCI) with stent placement: Rationale and design of the ENTRUST-AF PCI trial.

PubMed

Vranckx, Pascal; Lewalter, Thorsten; Valgimigli, Marco; Tijssen, Jan G; Reimitz, Paul-Egbert; Eckardt, Lars; Lanz, Hans-Joachim; Zierhut, Wolfgang; Smolnik, Rüdiger; Goette, Andreas

2018-02-01

The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored. The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis. The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB.

Improving Warfarin Management Within the Medical Home: A Health-System Approach.

PubMed

Rose, Anne E; Robinson, Erin N; Premo, Joan A; Hauschild, Lori J; Trapskin, Philip J; McBride, Ann M

2017-03-01

Anticoagulation clinics have been considered the optimal strategy for warfarin management with demonstrated improved patient outcomes through increased time in therapeutic international normalized ratio (INR) range, decreased critical INR values, and decreased anticoagulation-related adverse events. However, not all health systems are able to support a specialized anticoagulation clinic or may see patient volume exceed available anticoagulation clinic resources. The purpose of this study was to utilize an anticoagulation clinic model to standardize warfarin management in a primary care clinic setting. A warfarin management program was developed that included standardized patient assessment, protocolized warfarin-dosing algorithm, and electronic documentation and reporting tools. Primary care clinics were targeted for training and implementation of this program. The warfarin management program was applied to over 2000 patients and implemented at 39 clinic sites. A total of 160 nurses and 15 pharmacists were trained on the program. Documentation of warfarin dose and date of the next INR increased from 70% to 90% (P <.0001), documentation occurring within 24 hours of the INR result increased from 75% to 87% (P <.0001), and monitoring the INR at least every 4 weeks increased from 71% to 83% (P <.0001) per patient encounter. Time in therapeutic INR range improved from 65% to 75%. Incorporating a standardized approach to warfarin management in the primary care setting significantly improves warfarin-related documentation and time in therapeutic INR range. Copyright © 2016 Elsevier Inc. All rights reserved.

Nebulized anticoagulants in lung injury in critically ill patients—an updated systematic review of preclinical and clinical studies

PubMed Central

Juschten, Jenny; Tuinman, Pieter R.; Juffermans, Nicole P.; Dixon, Barry; Levi, Marcel

2017-01-01

Pneumonia, inhalation trauma and acute respiratory distress syndrome (ARDS), typical causes of lung injury in critically ill patients, are all three characterized by dysregulated inflammation and coagulation in the lungs. Nebulized anticoagulants are thought to have beneficial effects as they could attenuate pulmonary coagulopathy and maybe even affect pulmonary inflammation. A systematic search of the medical literature was performed using terms referring to aspects of the condition (‘pneumonia’, ‘inhalation trauma’ and ‘ARDS’), the intervention (‘nebulized’, ‘vaporized’, and ‘aerosolized’) and anticoagulants limited to agents that are commercially available and frequently given or tested in critically ill patients [‘heparin’, ‘danaparoid’, ‘activated protein C’ (APC), ‘antithrombin’ (AT) and ‘tissue factor pathway inhibitor’ (TFPI)]. The systematic search identified 16 articles reporting on preclinical studies and 11 articles reporting on human trials. All nebulized anticoagulants attenuate pulmonary coagulopathy in preclinical studies using various models for lung injury, but the effects on inflammation are less consistent. Nebulized heparin, danaparoid and TFPI, but not APC and AT also reduced systemic coagulation. Nebulized heparin in lung injury patients shows contradictory results, and there is concern over systemic side effects of this strategy. Future studies need to focus on the way to nebulize anticoagulants, as well as on efficient but safe dosages, and other side effects. PMID:29264361

Is there a role for pharmacokinetic/pharmacodynamic-guided dosing for novel oral anticoagulants?

PubMed

Chan, Noel; Sager, Philip T; Lawrence, Jack; Ortel, Thomas's; Reilly, Paul; Berkowitz, Scott; Kubitza, Dagmar; Eikelboom, John; Florian, Jeffry; Stockbridge, Norman; Rose, Martin; Temple, Robert; Seltzer, Jonathan H

2018-05-01

The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting. Copyright © 2017. Published by Elsevier Inc.

Contemporary Strategies in the Management of Civilian Neck Zone II Vascular Trauma

PubMed Central

Karaolanis, Georgios; Maltezos, Konstantinos; Bakoyiannis, Chris; Georgopoulos, Sotiris

2017-01-01

Neck trauma is the leading cause of death mainly in younger persons posing to surgeons the dilemma whether to proceed with reconstruction of vascular injuries either in the presence of coma or in severe neurological deficit. Vascular injuries in zone II predominate over the other injuries located in zones I/III of the neck. Conventional open repair of carotid injuries with primary closure or interposition grafting is always recommended due to the effective long-term results for penetrating injuries or for patients unfit for endovascular intervention. In cases of blunt trauma, anticoagulation or antiplatelet therapy should be administered first in neurologically stable patients. In case of worsening of the neurological status of the patient despite adequate anticoagulation endovascular means should be considered in cases of appropriate anatomy of the arterial trauma. We provide an update on penetrating/blunt trauma in zone II of the neck, giving emphasis on the anticoagulant and endovascular treatment. PMID:29034244

Evaluating the impact of new anticoagulants in the hospital setting

PubMed Central

Braidy, Nady; Bui, Khai; Bajorek, Beata

2010-01-01

The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives. Objective To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing. Method A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009). Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials. Results Data were collected for 67 patients treated with either warfarin (n=46) or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)). The use of dabigatran in VTE/stroke prevention was found to be more cost- effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33%) were factored into costing. Conclusion This study highlights the potential cost- effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients. PMID:25132883

Thromboprophylaxis for Patients with High-risk Atrial Fibrillation and Flutter Discharged from the Emergency Department.

PubMed

Vinson, David R; Warton, E Margaret; Mark, Dustin G; Ballard, Dustin W; Reed, Mary E; Chettipally, Uli K; Singh, Nimmie; Bouvet, Sean Z; Kea, Bory; Ramos, Patricia C; Glaser, David S; Go, Alan S

2018-03-01

Many patients with atrial fibrillation or atrial flutter (AF/FL) who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED). This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation. Of 312 eligible patients, 128 (41.0%) were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82-0.96); ED cardiology consultation (aOR 1.89, 95% CI [1.10-3.23]); and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35-5.21]). Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%), the most common of which were deferring the shared decision-making process to the patient's outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm. Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population.

Preemptive Anticoagulation in Patients With a High Pretest Probability of Pulmonary Embolism: Are Guidelines Followed?

PubMed

Willoughby, Laura; Adams, Daniel M; Evans, R Scott; Lloyd, James F; Stevens, Scott M; Woller, Scott C; Bledsoe, Joseph R; Aston, Valerie T; Wilson, Emily L; Elliott, C Gregory

2018-05-01

Guidelines suggest anticoagulation of patients with high pretest probability of pulmonary embolism (PE) while awaiting diagnostic test results (preemptive anticoagulation). Data relevant to the practice of preemptive anticoagulation are not available. We reviewed 3,500 consecutive patients who underwent CT pulmonary angiography (CTPA) at two EDs. We classified the pretest probability for PE using the revised Geneva Score (RGS) as low (RGS 0-3), intermediate (RGS 4-10), or high (RGS 11-18). We classified patients with a high pretest probability of PE as receiving preemptive anticoagulation if therapeutic anticoagulation was given before CTPA completion. Patients with a high bleeding risk and those receiving treatment for DVT before CTPA were excluded from the preemptive anticoagulation analysis. We compared the time elapsed between ED registration and CTPA completion for patients with a low, intermediate, and high pretest probability for PE. We excluded three of 3,500 patients because CTPA preceded ED registration. Of the remaining 3,497 patients, 167 (4.8%) had a high pretest probability for PE. After excluding 29 patients for high bleeding risk and 21 patients who were treated for DVT prior to CTPA, only two of 117 patients (1.7%) with a high pretest probability for PE received preemptive anticoagulation. Furthermore, 37 of the remaining 115 patients (32%) with a high pretest probability for PE had a preexisting indication for anticoagulation but did not receive preemptive anticoagulation. The time from ED registration to CTPA completion did not differ based on the pretest probability of PE. Physicians rarely use preemptive anticoagulation in patients with a high pretest probability for PE. Clinicians do not expedite CTPA examinations for patients with a high pretest probability for PE. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Disease management: atrial fibrillation and home monitoring.

PubMed

Ricci, Renato Pietro

2013-06-01

Device-detected atrial fibrillation (AF) episodes predict poor clinical outcome regardless of symptoms. Potential benefits of remote monitoring are early arrhythmia detection and patient continuous monitoring. Several studies of device remote monitoring consistently demonstrated that AF represents the most common clinical alert and that detailed information on arrhythmia onset, duration, and burden as well as on the ventricular rate may be early available for clinical evaluation. Reaction time to AF alerts was very short in all series involving either pacemakers or defibrillators and action ability of AF alerts was very high. In the Home Guide Registry, in which 1650 patients were enrolled, AF was detected in 16.3% of patients and represented 36% of all cardiovascular events during the follow-up. Timely anticoagulation introduction in asymptomatic patients may impact on the stroke rate. According to the results of repeated Monte Carlo simulations based on a real population of 166 patients, daily monitoring may reduce the 2-year stroke risk by 9-18% with an absolute reduction of 0.2-0.6%, compared with conventional inter-visit intervals of 6-12 months. In the COMPAS trial, the incidence of hospitalizations for atrial arrhythmias and related stroke was significantly higher in the control group than in the remote monitoring group. Major questions will be addressed by the ongoing IMPACT trial in which a remote monitoring guided anticoagulation strategy based on AF detection will be compared with a physician-directed standard strategy. In patients with heart failure, AF early detection combined with other indexes may help prevent hospitalizations.

Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

PubMed

Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

2004-12-01

Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

PubMed Central

Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

2013-01-01

Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

Venous Thromboembolism Requiring Extended Anticoagulation Among HIV-Infected Patients in a Rural, Resource-Constrained Setting in Western Kenya.

PubMed

Kanyi, John; Karwa, Rakhi; Pastakia, Sonak Dinesh; Manji, Imran; Manyara, Simon; Saina, Collins

2017-05-01

HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment. To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya. A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound-confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation. A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04. This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Polyguluronate sulfate, polymannuronate sulfate, and their oligosaccharides have antithrombin III- and heparin cofactor II-independent anticoagulant activity

NASA Astrophysics Data System (ADS)

Zeng, Xuan; Lan, Ying; Zeng, Pengjiao; Guo, Zhihua; Hao, Cui; Zhang, Lijuan

2017-04-01

Cardiovascular disease is the leading causes of death. However, the complications can be treated with heparin and heparinoids, such as heparin pentasaccharide Fondaparinux, dermatan sulfate, and PSS made from alginate extracted from brown seaweeds by chemical sulfation. Alginate is composed of a linear backbone of polymannuronate (PM), polyguluronate (PG), and alternate residues of mannuronic acid and guluronic acid. It is unknown if heparin and sulfated PG (PGS)/PM (PMS) have the same or different anticoagulant molecular targets. In the current study, the anticoagulant activities of PGS, PMS, and their oligosaccharides were directly compared to that of heparin, Fondaparinux, and dermatan sulfate by the activated partial thrombinplastin time (aPTT) assay using normal, antithrombin III (ATIII)-deficient, heparin co-factor II (HCII)-deficient, and ATIII- and HCII-double deficient human plasmas. Our results showed that PGS, PMS, and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested. As expected, heparin was the best anticoagulant in normal plasma. Moreover, PGS, PGS6, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma. Most strikingly, PGS, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than that of heparin in ATIII- and HCII-double deficient human plasma. The results revealed for the first time that sulfated alginate had ATIII- and HCII-independent anticoagulant activities. Therefore, developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era.

PubMed

Toth, Peter P

2016-01-01

Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism.

Heparin bridge therapy and post-polypectomy bleeding.

PubMed

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-12-07

To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB ( P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB ( P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

Cost-effectiveness of lower extremity compression ultrasound in emergency department patients with a high risk of hemodynamically stable pulmonary embolism.

PubMed

Ward, Michael J; Sodickson, Aaron; Diercks, Deborah B; Raja, Ali S

2011-01-01

Computed tomography angiograms (CTAs) for patients with suspected pulmonary embolism (PE) are being ordered with increasing frequency from the emergency department (ED). Strategies are needed to safely decrease the utilization of CTs to control rising health care costs and minimize the associated risks of anaphylaxis, contrast-induced nephropathy, and radiation-induced carcinogenesis. The use of compression ultrasonography (US) to identify deep vein thromboses (DVTs) in hemodynamically stable patients with signs and symptoms suggestive of PE is highly specific for the diagnosis of PE and may represent a cost-effective alternative to CT imaging.   The objective was to analyze the cost-effectiveness of a selective CT strategy incorporating the use of compression US to diagnose and treat DVT in patients with a high pretest probability of PE. The authors constructed a decision analytic model to evaluate the scenario of an otherwise healthy 59-year-old female in whom PE was being considered as a diagnosis. Two strategies were used. The selective CT strategy began with a screening compression US. Negative studies were followed up with a CTA, while patients with positive studies identifying a DVT were treated as though they had a PE and were anticoagulated. The universal CT strategy used CTA as the initial test, and anticoagulation was based on the CT result. Costs were estimated from the 2009 Medicare data for hospital reimbursement, and professional fees were obtained from the 2009 National Physician Fee Schedule. Clinical probabilities were obtained from existing published data, and sensitivity analyses were performed across plausible ranges for all clinical variables. In the base case, the selective CT strategy cost $1,457.70 less than the universal CT strategy and resulted in a gain of 0.0213 quality-adjusted life-years (QALYs). Sensitivity analyses confirm that the selective CT strategy is dominant above both a pretest probability for PE of 8.3% and a compression US specificity of 87.4%. A selective CT strategy using compression US is cost-effective for patients provided they have a high pretest probability of PE. This may reduce the need for, and decrease the adverse events associated with, CTAs. © 2010 by the Society for Academic Emergency Medicine.

Heparin-induced thrombocytopenia and heart operation: management with tedelparin.

PubMed

Altés, A; Martino, R; Gari, M; Cámara, M L; Garín, R; Casas, J I; Fontcuberta, J

1995-02-01

Anticoagulation for cardiopulmonary bypass in the infrequent clinical setting of thrombocytopenia associated with the use of unfractionated heparin is a very serious problem. We describe a case in which a low-molecular-weight heparin (tedelparin) was selected for this purpose based on a platelet aggregation test, permitting adequate anticoagulation during cardiopulmonary bypass for valve replacement. This case report might help establish an adequate anticoagulation protocol when faced with a patient suffering from this condition.

Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

PubMed

Violi, Francesco; Lip, Gregory Yh; Pignatelli, Pasquale; Pastori, Daniele

2016-03-01

Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs. Restriction of dietary vitamin K intake does not seem to be a valid strategy to improve anticoagulation quality with VKAs. It would be, perhaps, more relevant to maintain stable dietary habit, avoiding wide changes in the intake of vitamin K.

Aspirin versus anticoagulation for prevention of venous thromboembolism major lower extremity orthopedic surgery: a systematic review and meta-analysis.

PubMed

Drescher, Frank S; Sirovich, Brenda E; Lee, Alexandra; Morrison, Daniel H; Chiang, Wesley H; Larson, Robin J

2014-09-01

Hip fracture surgery and lower extremity arthroplasty are associated with increased risk of both venous thromboembolism and bleeding. The best pharmacologic strategy for reducing these opposing risks is uncertain. To compare venous thromboembolism (VTE) and bleeding rates in adult patients receiving aspirin versus anticoagulants after major lower extremity orthopedic surgery. Medline, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library through June 2013; reference lists, ClinicalTrials.gov, and scientific meeting abstracts. Randomized trials comparing aspirin to anticoagulants for prevention of VTE following major lower extremity orthopedic surgery. Two reviewers independently extracted data on rates of VTE, bleeding, and mortality. Of 298 studies screened, 8 trials including 1408 participants met inclusion criteria; all trials screened participants for deep venous thrombosis (DVT). Overall rates of DVT did not differ statistically between aspirin and anticoagulants (relative risk [RR]: 1.15 [95% confidence interval {CI}: 0.68-1.96]). Subgrouped by type of surgery, there was a nonsignificant trend favoring anticoagulation following hip fracture repair but not knee or hip arthroplasty (hip fracture RR: 1.60 [95% CI: 0.80-3.20], 2 trials; arthroplasty RR: 1.00 [95% CI: 0.49-2.05], 5 trials). The risk of bleeding was lower with aspirin than anticoagulants following hip fracture repair (RR: 0.32 [95% CI: 0.13-0.77], 2 trials), with a nonsignificant trend favoring aspirin after arthroplasty (RR: 0.63 [95% CI: 0.33-1.21], 5 trials). Rates of pulmonary embolism were too low to provide reliable estimates. Compared with anticoagulation, aspirin may be associated with higher risk of DVT following hip fracture repair, although bleeding rates were substantially lower. Aspirin was similarly effective after lower extremity arthroplasty and may be associated with lower bleeding risk. Journal of Hospital Medicine 2014;9:579-585. © 2014 Society of Hospital Medicine. © 2014 Society of Hospital Medicine.

Investigations of blood ammonia analysis: Test matrices, storage, and stability.

PubMed

Goldstein, Brittany N; Wesler, Jordan; Nowacki, Amy S; Reineks, Edmunds; Natowicz, Marvin R

2017-06-01

An assessment of blood ammonia concentration is common medical practice in the evaluation of an individual with an unexplained mental status change or coma. The determination of a blood ammonia level is most commonly done using a glutamate dehydrogenase (GLDH)-based assay, although there are many potential sources of artifact and the literature is inconsistent regarding key preanalytic issues. Using a GLDH-based assay, we first investigated matrix effects using three anticoagulants: heparin, EDTA and oxalate. Heparin-anticoagulated plasma was substantially less precise than EDTA- and oxalate-anticoagulated plasma. Oxalate-anticoagulated plasma showed a greater baseline of apparent ammonia than either heparin- or EDTA-derived plasma, presumably due to interferants. We then evaluated the stability of EDTA-anticoagulated plasma for assessment of ammonia when stored at 4°C,-14°C or -70°C. There was a linear increase of ammonia with storage at both 4°C and -14°C. Plasma kept at -70°C for up to three weeks showed no change in measured ammonia relative to the baseline determination. This work clarifies preanalytic conditions for which a precise determination of ammonia can be accomplished using a GLDH-based assay. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effective estimation of correct platelet counts in pseudothrombocytopenia using an alternative anticoagulant based on magnesium salt

PubMed Central

Schuff-Werner, Peter; Steiner, Michael; Fenger, Sebastian; Gross, Hans-Jürgen; Bierlich, Alexa; Dreissiger, Katrin; Mannuß, Steffen; Siegert, Gabriele; Bachem, Maximilian; Kohlschein, Peter

2013-01-01

Pseudothrombocytopenia remains a challenge in the haematological laboratory. The pre-analytical problem that platelets tend to easily aggregate in vitro, giving rise to lower platelet counts, has been known since ethylenediamine-tetra acetic acid EDTA and automated platelet counting procedures were introduced in the haematological laboratory. Different approaches to avoid the time and temperature dependent in vitro aggregation of platelets in the presence of EDTA were tested, but none of them proved optimal for routine purposes. Patients with unexpectedly low platelet counts or flagged for suspected aggregates, were selected and smears were examined for platelet aggregates. In these cases patients were asked to consent to the drawing of an additional sample of blood anti-coagulated with a magnesium additive. Magnesium was used in the beginning of the last century as anticoagulant for microscopic platelet counts. Using this approach, we documented 44 patients with pseudothrombocytopenia. In all cases, platelet counts were markedly higher in samples anti-coagulated with the magnesium containing anticoagulant when compared to EDTA-anticoagulated blood samples. We conclude that in patients with known or suspected pseudothrombocytopenia the magnesium-anticoagulant blood samples may be recommended for platelet counting. PMID:23808903

Overview of a pharmacist anticoagulation certificate program.

PubMed

Kirk, Julienne K; Edwards, Rebecca; Brewer, Andrew; Miller, Cathey; Bray, Bryan; Groce, James B

2017-07-01

To describe the design of an ongoing anticoagulation certificate program and annual renewal update for pharmacists. Components of the anticoagulation certificate program include home study, pre- and posttest, live sessions, case discussions with evaluation and presentation, an implementation plan, and survey information (program evaluation and use in practice). Clinical reasoning skills were assessed through case work-up and evaluation prior to live presentation. An annual renewal program requires pharmacists to complete home study and case evaluations. A total of 361 pharmacists completed the anticoagulation certificate program between 2002 and 2015. Most (62%) practiced in ambulatory care and 38% in inpatient care settings (8% in both). In the past four years, 71% were working in or starting anticoagulation clinics in ambulatory and inpatient settings. In their evaluations of the program, an average of 90% of participants agreed or strongly agreed the lecture material was relevant and objectives were met. Pharmacists are able to apply knowledge and skills in management of anticoagulation. This structured practice-based continuing education program was intended to enhance pharmacy practice and has achieved that goal. The certificate program in anticoagulation was relevant to pharmacists who attended the program. Copyright © 2017. Published by Elsevier Inc.

Management of Bleeding With Non-Vitamin K Antagonist Oral Anticoagulants in the Era of Specific Reversal Agents.

PubMed

Ruff, Christian T; Giugliano, Robert P; Antman, Elliott M

2016-07-19

Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed. Important steps in minimizing bleeding risks with NOACs include dose adjustment of the agents in the setting of renal dysfunction and avoidance of the concomitant use of other antithrombotic agents if feasible. Laboratory measurement of the anticoagulant effect of NOACs is best accomplished with specialized assays, although some of the more widely available coagulation tests can provide information that is potentially useful to clinicians. Nonspecific hemostatic agents such as prothrombin complex concentrates and recombinant factor VIIa can be used to reverse the effect of NOACs. More specific reversing agents include the approved humanized monoclonal antibody fragment idarucizumab for reversing the effects of dabigatran, the investigational factor Xa decoy andexanet alfa, and the synthetic small molecule ciraparantag. Both andexanet and ciraparantag have been reported to reverse the effects of the anti-Xa NOACs (rivaroxaban, apixaban, and edoxaban), and a number of other anticoagulant agents in common clinical use, as well. © 2016 American Heart Association, Inc.

Heparin bridge therapy and post-polypectomy bleeding

PubMed Central

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-01-01

AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants. PMID:28018108

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

PubMed

Fareed, Jawed; Adiguzel, Cafer; Thethi, Indermohan

2011-03-28

The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. MEDLINE and EMBASE databases were searched to identify relevant original articles. Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved more than two thirds agreement on each recommendation. The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations. It is hoped that this guideline will serve as a resource and will stimulate investigators to conduct more research and to expand on the evidence base on the topic of anticoagulation therapy for CPB. Copyright © 2018 The Society of Thoracic Surgeons, International Anesthesia Research Society, and the American Society of ExtraCorporeal Technology. Published by Elsevier Inc. All rights reserved.

Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor UHRA

PubMed Central

Abraham, Libin; Kapopara, Piyushkumar R.; Lai, Benjamin F. L.; Shenoi, Rajesh A.; Rosell, Federico I.; Conway, Edward M.; Pryzdial, Edward L. G.; Haynes, Charles A.

2017-01-01

Anticoagulant therapy–associated bleeding and pathological thrombosis pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids exhibit both nonspecific binding and adverse effects on blood clotting that limit their use. Indeed, the polycation used to counteract heparin-associated bleeding in surgical settings, protamine, exhibits adverse effects. To address these clinical shortcomings, we developed a synthetic polycation, Universal Heparin Reversal Agent (UHRA), which is nontoxic and can neutralize the anticoagulant activity of heparins and the prothrombotic activity of polyP. Sharply contrasting protamine, we show that UHRA does not interact with fibrinogen, affect fibrin polymerization during clot formation, or abrogate plasma clotting. Using scanning electron microscopy, confocal microscopy, and clot lysis assays, we confirm that UHRA does not incorporate into clots, and that clots are stable with normal fibrin morphology. Conversely, protamine binds to the fibrin clot, which could explain how protamine instigates clot lysis and increases bleeding after surgery. Finally, studies in mice reveal that UHRA reverses heparin anticoagulant activity without the lung injury seen with protamine. The data presented here illustrate that UHRA could be safely used as an antidote during adverse therapeutic modulation of hemostasis. PMID:28034889

Stroke Prevention in Atrial Fibrillation: Focus on Latin America

PubMed Central

Massaro, Ayrton R.; Lippp, Gregory Y. H.

2016-01-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with an estimated prevalence of 1-2% in North America and Europe. The increased prevalence of AF in Latin America is associated with an ageing general population, along with poor control of key risk factors, including hypertension. As a result, stroke prevalence and associated mortality have increased dramatically in the region. Therefore, the need for effective anticoagulation strategies in Latin America is clear. The aim of this review is to provide a contemporary overview of anticoagulants for stroke prevention. The use of vitamin K antagonists (VKAs, eg, warfarin) and aspirin in the prevention of stroke in patients with AF in Latin America remains common, although around one fifth of all AF patients receive no anticoagulation. Warfarin use is complicated by a lack of access to effective monitoring services coupled with an unpredictable pharmacokinetic profile. The overuse of aspirin is associated with significant bleeding risks and reduced efficacy for stroke prevention in this patient group. The non-VKA oral anticoagulants (NOACbs) represent a potential means of overcoming many limitations associated with VKA and aspirin use, including a reduction in the need for monitoring and a reduced risk of hemorrhagic events. The ultimate decision of which anticoagulant drug to utilize in AF patients depends on a multitude of factors. More research is needed to appreciate the impact of these factors in the Latin American population and thereby reduce the burden of AF-associated stroke in this region. PMID:28558081

Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot).

PubMed

Lenarczyk, Radosław; Mitręga, Katarzyna; Mazurek, Michał; Janion, Marianna; Opolski, Grzegorz; Drożdż, Jarosław; Streb, Witold; Fuglewicz, Artur; Sokal, Adam; Laroche, Cécile; Lip, Gregory Y H; Kalarus, Zbigniew

2016-01-01

Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In-hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results.

Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in Older Inpatients: A Study Proposal

PubMed Central

Quantin, Catherine; Reich, Oliver; Tuppin, Philippe; Fagot-Campagna, Anne; Paccaud, Fred; Peytremann-Bridevaux, Isabelle; Burnand, Bernard

2017-01-01

Background Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients. Objective This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients. Methods GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients’ conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data-based algorithms, (3) empirical measurement of indicators using linked administrative health data, (4) validation of indicators, (5) analyses of geographic and temporal variations for reliable and valid indicators, and (6) data visualization. Results Study populations will consist of 166,670 Swiss and 5,902,037 French residents aged 65 years and older admitted to an acute care hospital at least once during the 2012-2014 period and insured for at least 1 year before admission and 1 year after discharge. We will extract Swiss data from the Helsana Group data warehouse and French data from the national health insurance information system (SNIIR-AM). The study has been approved by Swiss and French ethics committees and regulatory organizations for data protection. Conclusions Validated GPSIs and GQIs should help support and drive quality and safety improvement in older inpatients, inform health care stakeholders, and enable international comparisons. We discuss several limitations relating to the representativeness of study populations, accuracy of administrative health data, methods used for GPSI criterion validity assessment, and potential confounding bias in comparisons based on GQIs, and we address these limitations to strengthen study feasibility and validity. PMID:28495660

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

PubMed

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-09-01

cost of anticoagulation with dabigatran is largely based on estimation of complication rates derived from clinical trials. to investigate cost of anticoagulation with dabigatran in comparison with warfarin in clinical practice. a prospective observational study of patients with non-vavular atrial fibrillation (NVAF) referred to anticoagulation clinic. Patients were interviewed (4-6 weekly by telephone) about bleeding events. Costs of anticoagulation were calculated as: (i) drug cost, (ii) international normalised ratio (INR) monitoring cost and (iii) bleeding cost. For cost calculation of dabigatran, INR monitoring cost was omitted. a total of 402 patients were included and followed up for a mean (SD) of 19 (8.1) months. Annual cost of anticoagulation was £207.3 and £1,573.5 per patient for warfarin and dabigatran, respectively. Drug price constituted 13.6% of the total cost for warfarin and 94% for dabigatran. Total cost of anticoagulation to prevent one stroke per year was £6,219, £28,086.5 and £25,181 for warfarin, dabigatran 110 and 150 mg, respectively. cost of anticoagulation is mainly driven by drug price for dabigatran and quality of INR control for warfarin. Until the price of dabigatran is reviewed, warfarin remains suitable for the majority of patients with NVAF.

Risk stratification and management of acute pulmonary embolism.

PubMed

Becattini, Cecilia; Agnelli, Giancarlo

2016-12-02

The clinical management of patients with acute pulmonary embolism is rapidly changing over the years. The widening spectrum of clinical management strategies for these patients requires effective tools for risk stratification. Patients at low risk for death could be candidates for home treatment or early discharge. Clinical models with high negative predictive value have been validated that could be used to select patients at low risk for death. In a major study and in several meta-analyses, thrombolysis in hemodynamically stable patients was associated with unacceptably high risk for major bleeding complications or intracranial hemorrhage. Thus, the presence of shock or sustained hypotension continues to be the criterion for the selection of candidates for thrombolytic treatment. Interventional procedures for early revascularization should be reserved to selected patients until further evidence is available. No clinical advantage is expected with the insertion of a vena cava filter in the acute-phase management of patients with acute pulmonary embolism. Direct oral anticoagulants used in fixed doses without laboratory monitoring showed similar efficacy (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.70-1.12) and safety (OR, 0.89; 95% CI, 0.77-1.03) in comparison with conventional anticoagulation in patients with acute pulmonary embolism. Based on these results and on their practicality, direct oral anticoagulants are the agents of choice for the treatment of the majority of patients with acute pulmonary embolism. © 2016 by The American Society of Hematology. All rights reserved.

Use of apixaban after development of suspected rivaroxaban-induced hepatic steatosis; a case report.

PubMed

Anastasia, Emily J; Rosenstein, Robert S; Bergsman, Jeffrey A; Parra, David

2015-09-01

Postmarketing reports have emerged associating rivaroxaban with drug-induced liver injury (DILI); however, management strategies of patients with suspected rivaroxaban-induced liver injury requiring continued anticoagulation have not been published. The present report describes a 67-year-old male with atrial fibrillation receiving rivaroxaban who developed a 16-fold elevation in alanine transaminase, a nearly two-fold elevation in total bilirubin, and ultrasound confirmed hepatic steatosis. The patient was switched from rivaroxaban to apixaban with subsequent rapid resolution of laboratory abnormalities. Rapid improvement in liver function tests despite use of an alternative factor Xa inhibitor suggests that rivaroxaban's mechanism of hepatotoxicity may be unrelated to its pharmacologic action. When using rivaroxaban, clinicians should be aware of the small but potentially serious risk of DILI. Because most anticoagulants have been associated with DILI, selection of an alternative anticoagulant may be challenging; however, the use of apixaban in this case suggests it may be a reasonable alternative.

Regional citrate anticoagulation for continuous renal replacement therapy in severe burns-a retrospective analysis of a protocol-guided approach.

PubMed

Gille, Jochen; Sablotzki, Armin; Malcharek, Michael; Raff, Thomas; Mogk, Martin; Parentin, Torsten

2014-12-01

For critically ill patients, the use of regional citrate anticoagulation as part of continuous renal replacement therapy (CRRT) has become increasingly common in recent years. However, there are scarce data on the use of this technique in patients with burns. The aim of this study was to examine the effectiveness, feasibility and complications of regional citrate anticoagulation for CRRT in burn patients, as well as the effects on coagulation and the electrolyte and acid-base balance. This retrospective study included all patients who received renal replacement therapy with citrate anticoagulation to treat acute kidney injury (AKI) between January 1, 2004 and December 31, 2009 at the burn unit of St. Georg Hospital GmbH in Leipzig. During the examination period, 18 patients were treated using CRRT with regional citrate anticoagulation (CVVHDF in the pre-dilution mode). The median patient age was 64 years (49.5; 71), with a median TBSA of 42.5% (33.25; 52.5) and a median ABSI score of 10 (9; 10). The CRRT was initiated on a median of 6 days (4; 8.75) after admission to the hospital and continued for a median duration of 7 days (5; 8). The median dialysis dose was 38.2mlkgBW(-1)h(-1) (31.8; 42.1). The median effective filter operation time was 67h (46; 72). No relevant disorders associated with acid-base balance, electrolytes or coagulation occurred, and there were no bleeding complications. In terms of bleeding risk and electrolyte and acid-base balance, regional citrate anticoagulation may be considered to be an effective, safe and user-friendly procedure for patients with severe burns and AKI. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

PubMed Central

Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

2015-01-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

The incidence of traumatic intracranial hemorrhage in head-injured older adults transported by EMS with and without anticoagulant or antiplatelet use.

PubMed

Nishijima, Daniel Kiden; Gaona, Samuel D; Waechter, Trent; Maloney, Ric; Blitz, Adam; Elms, Andrew R; Farrales, Roel D; Montoya, James; Bair, Troy; Howard, Calvin; Gilbert, Megan; Trajano, Renee; Hatchel, Kaela; Faul, Mark; Bell, Jeneita M; Coronado, Victor; Vinson, David R; Ballard, Dustin W; Tancredi, Daniel J; Garzon, Hernando; Mackey, Kevin E; Shahlaie, Kiarash; Holmes, James F

2017-11-06

Field triage guidelines recommend transport of head-injured patients on anticoagulants or antiplatelets to a higher-level trauma center based on studies suggesting a high incidence of traumatic intracranial hemorrhage (tICH). We compared the incidence of tICH in older adults transported by EMS with and without anticoagulation or antiplatelet use and evaluated the accuracies of different sets of field triage criteria to identify tICH. This was a prospective, observational study at 5 EMS agencies and 11 hospitals. Older adults (≥55 years) with head trauma and transported by EMS from Aug 2015 to Sept 2016 were eligible. EMS providers completed standardized data forms and patients were followed through ED or hospital discharge. We enrolled 1,304 patients; 1147 (88%) received a cranial CT scan and were eligible for analysis. 434 (33%) patients had anticoagulant or antiplatelet use and 112 (10%) had tICH. The incidence of tICH in patients with (11%, 95%CI 8-14%) and without (9%, 95%CI 7-11%) anticoagulant or antiplatelet use was similar. Anticoagulant or antiplatelet use was not predictive of tICH on adjusted analysis. Steps 1-3 criteria alone were not sensitive in identifying tICH (27%) while the addition of anticoagulant or antiplatelet criterion improved sensitivity (63%). Other derived sets of triage criteria were highly sensitive (>98%) but poorly specific (<11%). The incidence of tICH was similar between patients with and without anticoagulant or antiplatelet use. Use of anticoagulant or antiplatelet medications was not a risk factor for tICH. We were unable to identify a set of triage criteria that was accurate for trauma center need.

Frequency of "Pocket" Hematoma in Patients Receiving Vitamin K Antagonist and Antiplatelet Therapy at the Time of Pacemaker or Cardioverter Defibrillator Implantation (from the POCKET Study).

PubMed

Malagù, Michele; Trevisan, Filippo; Scalone, Antonella; Marcantoni, Lina; Sammarco, Giuseppe; Bertini, Matteo

2017-04-01

In patients undergoing cardiac device implantation, anticoagulant and antiplatelet therapy are associated with an increased risk of pocket hematoma. In case of vitamin K antagonist therapy, a strategy of continued warfarin with no heparin bridge showed a reduction of pocket hematoma. Evidence regarding antiplatelet therapy management is limited. This is a single-center observational study which reflects our systematic approach to the problem. In 2012, we proposed an improved management protocol for anticoagulant and antiplatelet therapy (no-bridge protocol) based on individual thromboembolic risk stratification, noninterruption of oral anticoagulation, no bridge with heparin and elastic adherence compression bandage. The primary end point was the incidence of clinically significant pocket hematoma in the first 30 days after implantation. A total of 1,035 patients were enrolled, of whom 522 received the standard management and 513 the new protocol. The primary end point occurred in 34 patients of the standard management group and 8 patients of the no-bridge protocol group (6.5% vs 1.6%, p <0.001). Patients in the standard management group had a higher incidence of pocket infections (2.3% vs 0.6%, p = 0.02), lead dislodgements (4.8% vs 2.1%, p = 0.02), and thromboembolic events (1.3% vs 0.0%, p <0.01). On a multivariate analysis, heparin and coronary artery disease were independent predictors of pocket hematoma (relative risk [RR] 3.48, 95% confidence interval [CI] 1.55 to 7.83 and RR 2.43, 95% CI 1.25 to 4.76, respectively), whereas the no-bridge protocol was associated with a reduction of pocket hematoma (RR 0.33, 95% CI 0.14 to 0.76). New anticoagulant and antiplatelet therapy management protocol was associated with a reduced incidence of clinically significant pocket hematomas, thromboembolic events, pocket infections, and lead dislodgements. Copyright © 2017 Elsevier Inc. All rights reserved.

[Concepts in anticoagulant therapy - past, present, and future].

PubMed

Graf, L

2012-11-01

The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

Geriatric Patient Safety Indicators Based on Linked Administrative Health Data to Assess Anticoagulant-Related Thromboembolic and Hemorrhagic Adverse Events in Older Inpatients: A Study Proposal.

PubMed

Le Pogam, Marie-Annick; Quantin, Catherine; Reich, Oliver; Tuppin, Philippe; Fagot-Campagna, Anne; Paccaud, Fred; Peytremann-Bridevaux, Isabelle; Burnand, Bernard

2017-05-11

Frail older people with multiple interacting conditions, polypharmacy, and complex care needs are particularly exposed to health care-related adverse events. Among these, anticoagulant-related thromboembolic and hemorrhagic events are particularly frequent and serious in older inpatients. The growing use of anticoagulants in this population and their substantial risk of toxicity and inefficacy have therefore become an important patient safety and public health concern worldwide. Anticoagulant-related adverse events and the quality of anticoagulation management should thus be routinely assessed to improve patient safety in vulnerable older inpatients. This project aims to develop and validate a set of outcome and process indicators based on linked administrative health data (ie, insurance claims data linked to hospital discharge data) assessing older inpatient safety related to anticoagulation in both Switzerland and France, and enabling comparisons across time and among hospitals, health territories, and countries. Geriatric patient safety indicators (GPSIs) will assess anticoagulant-related adverse events. Geriatric quality indicators (GQIs) will evaluate the management of anticoagulants for the prevention and treatment of arterial or venous thromboembolism in older inpatients. GPSIs will measure cumulative incidences of thromboembolic and bleeding adverse events based on hospital discharge data linked to insurance claims data. Using linked administrative health data will improve GPSI risk adjustment on patients' conditions that are present at admission and will capture in-hospital and postdischarge adverse events. GQIs will estimate the proportion of index hospital stays resulting in recommended anticoagulation at discharge and up to various time frames based on the same electronic health data. The GPSI and GQI development and validation process will comprise 6 stages: (1) selection and specification of candidate indicators, (2) definition of administrative data-based algorithms, (3) empirical measurement of indicators using linked administrative health data, (4) validation of indicators, (5) analyses of geographic and temporal variations for reliable and valid indicators, and (6) data visualization. Study populations will consist of 166,670 Swiss and 5,902,037 French residents aged 65 years and older admitted to an acute care hospital at least once during the 2012-2014 period and insured for at least 1 year before admission and 1 year after discharge. We will extract Swiss data from the Helsana Group data warehouse and French data from the national health insurance information system (SNIIR-AM). The study has been approved by Swiss and French ethics committees and regulatory organizations for data protection. Validated GPSIs and GQIs should help support and drive quality and safety improvement in older inpatients, inform health care stakeholders, and enable international comparisons. We discuss several limitations relating to the representativeness of study populations, accuracy of administrative health data, methods used for GPSI criterion validity assessment, and potential confounding bias in comparisons based on GQIs, and we address these limitations to strengthen study feasibility and validity. ©Marie-Annick Le Pogam, Catherine Quantin, Oliver Reich, Philippe Tuppin, Anne Fagot-Campagna, Fred Paccaud, Isabelle Peytremann-Bridevaux, Bernard Burnand. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 11.05.2017.

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

PubMed

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Standards of care issues with anticoagulation in real-world populations.

PubMed

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis.

PubMed

Lisman, Ton; Kleiss, Simone; Patel, Vishal C; Fisher, Caleb; Adelmeijer, Jelle; Bos, Sarah; Singanayagam, Arjuna; Stoy, Sidsel Hyldgaard; Shawcross, Debbie L; Bernal, William

2018-05-16

A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches. Fresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10-20%). Prothrombin complex concentrate increased thrombin generation 2-fold in controls and 2-4-fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50-60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23-54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47-100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11-38% in patients. These in vitro data suggest little prohemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved hemostasis. Furthermore, our data suggest the requirement for dose-adjustments of commonly used anticoagulants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sex and Gender Differences in Thromboprophylactic Treatment of Patients With Atrial Fibrillation After the Introduction of Non-Vitamin K Oral Anticoagulants.

PubMed

Loikas, Desirée; Forslund, Tomas; Wettermark, Björn; Schenck-Gustafsson, Karin; Hjemdahl, Paul; von Euler, Mia

2017-10-15

To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of bleeding in patients receiving direct oral anticoagulants

PubMed Central

Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

2017-01-01

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

[Stroke prevention in atrial fibrillation in Germany. Situational analysis of treatment reality based on retrospective data].

PubMed

Mergenthaler, Ulrike; Kostev, Karel; Moosmang, Sven; Thate-Waschke, Inga-Marion; Haas, Sylvia

2017-12-01

Guideline-based, risk-adjusted therapy with anticoagulants reduce thromboembolic stroke risk in patients with atrial fibrillation (AF). This study analyzed use of oral anticoagulation in German AF-patients. Access to anonymized patient records was made via IMS Health Disease Analyzer database (sample size: 113,619 patients with ICD-10 Code I48.-; observation period: 11/2010-10/2013). Results were subsequently extrapolated to all general practitioners' (GPs) and cardiological practices in Germany. In 2011 12-month AF-prevalence was extrapolated to 2.1 million patients (first diagnosed: n = 537.548). In 2012 AF-prevalence gone up to 2.2 million cases (first diagnosed: n = 537.548) and in 2013 to 2.8 million (first diagnosed: n = 636.571). Commonly prescribed oral anticoagulants (OAC) were vitamin K antagonists (VKA). Unstable INR setting, private health insurance, hospital admission, heart failure or hypertension increased probability of change from VKA to non-vitamin K antagonist oral anticoagulants (NOAC). 17.3-36.5% of patients with CHA 2 DS 2 -VASc-score ≥ 2 did not receive any thromboembolism prophylaxis; 38.5% with CHA 2 DS 2 -VASc-score = 0 received unnecessarily OACs. For 2013 a potential of 29.749 ischemic strokes in GP practices was calculated, which possibly can be avoided by thromboembolism prophylaxis according to guidelines. Risk-based anticoagulation showed requirements for optimization. Use of OACs, according to guideline recommendations, would minimize bleeding risks, reduce ischemic strokes and could release resources.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry.

PubMed

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph Gabriel

2015-01-01

Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. ISRCTN registry of clinical trials: ISRCTN43070564.

Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

PubMed Central

Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

2015-01-01

Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

Perinatal thrombosis: implications for mothers and neonates.

PubMed

O'Brien, Sarah H

2015-01-01

Stroke is more likely to occur in the perinatal period than any other time in childhood, and these events can lead to a lifetime of intellectual and motor disabilities, epilepsy, and behavioral challenges. This review describes the epidemiology and natural history of perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT), risk factors for these complications, recent evidence regarding treatment strategies, and current gaps in knowledge. Existing evidence demonstrates the multifactorial etiology of symptomatic ischemic stroke in neonates, which includes a combination of maternal, delivery, and neonatal factors. The importance of inherited thrombophilia in the pathophysiology and long-term outcomes of perinatal stroke requires additional study. At this time, there is no evidence to support routine extensive thrombophilia screening outside of a research setting. Despite the frequency of perinatal stroke and its association with substantial morbidity, treatment strategies are currently limited, and prevention strategies are nonexistent. Anticoagulation is rarely indicated in PAIS, and more work needs to focus on neuroprotective prevention and alternate treatment strategies. Anticoagulation does appear to be safe in CSVT and may prevent thrombus progression but clinical equipoise remains, and clinical trials are needed to obtain evidence regarding short- and long-term efficacy outcomes. © 2015 by The American Society of Hematology. All rights reserved.

A sensitive label-free immunosensor for detection α-Fetoprotein in whole blood based on anticoagulating magnetic nanoparticles.

PubMed

Xu, Tingting; Chi, Bo; Wu, Fan; Ma, Shangshang; Zhan, Shuyue; Yi, Meihui; Xu, Hong; Mao, Chun

2017-09-15

Accurate values of tumor markers in blood play an especially important role in the diagnosis of illness. Here, based on the combination of three techniques include anticoagulant technology, nanotechnology and biosensing technology, a sensitive label-free immunosensor with anti-biofouling electrode for detection α-Fetoprotein (AFP) in whole blood was developed by anticoagulating magnetic nanoparticles. The obtained products of Fe 3 O 4 -ɛ-PL-Hep nanoparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM), ζ-potential and vibrating sample magnetometry (VSM). Moreover, the blood compatibility of anticoagulating magnetic nanoparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Combining the anticoagulant property of heparin (Hep) and the good magnetism of Fe 3 O 4 , the Fe 3 O 4 -ɛ-PL-Hep nanoparticles could improve not only the anti-biofouling property of the electrode surface when they contact with whole blood, but also the stability and reproducibility of the proposed immunosensor. Thus, the prepared anticoagulating magnetic nanoparticles modified immunosensor for the detection of AFP showed excellent electrochemical properties with a wide concentration range from 0.1 to 100ng/mL and a low detection limit of 0.072ng/mL. Furthermore, five blood samples were assayed using the developed immunosensor. The results showed satisfactory accuracy with low relative errors. It indicated that our developed immunoassay was competitive and could be potentially used for the detection of whole blood samples directly. Copyright © 2017 Elsevier B.V. All rights reserved.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

PubMed

Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam

2017-05-01

This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.

Cerebral Amyloid Angiopathy: Diagnosis, Clinical Implications, and Management Strategies in Atrial Fibrillation.

PubMed

DeSimone, Christopher V; Graff-Radford, Jonathan; El-Harasis, Majd A; Rabinstein, Alejandro A; Asirvatham, Samuel J; Holmes, David R

2017-08-29

With an aging population, clinicians are more frequently encountering patients with atrial fibrillation who are also at risk of intracerebral hemorrhage due to cerebral amyloid angiopathy, the result of β-amyloid deposition in cerebral vessels. Cerebral amyloid angiopathy is common among elderly patients, and is associated with an increased risk of intracerebral bleeding, especially with the use of anticoagulation. Despite this association, this entity is absent in current risk-benefit analysis models, which may result in underestimation of the chance of bleeding in the subset of patients with this disease. Determining the presence and burden of cerebral amyloid angiopathy is particularly important when planning to start or restart anticoagulation after an intracerebral hemorrhage. Given the lack of randomized trial data to guide management strategies, we discuss a heart-brain team approach that includes clinician-patient shared decision making for the use of pharmacologic and nonpharmacologic approaches to diminish stroke risk. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clinical and safety outcomes associated with treatment of acute venous thromboembolism: a systematic review and meta-analysis.

PubMed

Castellucci, Lana A; Cameron, Chris; Le Gal, Grégoire; Rodger, Marc A; Coyle, Doug; Wells, Philip S; Clifford, Tammy; Gandara, Esteban; Wells, George; Carrier, Marc

2014-09-17

Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe. To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism. A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014. Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses. Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis. The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively. Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination. Using meta-analytic pooling, there were no statistically significant differences for efficacy and safety associated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.

Barriers and facilitators to reducing frequent laboratory testing for patients who are stable on warfarin: a mixed methods study of de-implementation in five anticoagulation clinics.

PubMed

Barnes, Geoffrey D; Misirliyan, Sevan; Kaatz, Scott; Jackson, Elizabeth A; Haymart, Brian; Kline-Rogers, Eva; Kozlowski, Jay; Krol, Gregory; Froehlich, James B; Sales, Anne

2017-07-14

Patients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative. Using a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice. From the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less frequent INR testing to 56% (46-66%) of eligible patients. Most survey responders (n = 24; 60%) agreed that an eligibility flag in the electronic medical record would be very helpful. Twenty-four (60%) respondents agreed that periodic, personalized feedback on use of less frequent INR testing would also be helpful. Leveraging information system notifications, reducing additional work load burden for participating patients and providers, and providing personalized feedback are strategies that may improve adoption and utilization new policies in anticoagulation clinics that focus on de-implementation.

Coagulopathy and transfusion therapy in pediatric liver transplantation

PubMed Central

Nacoti, Mirco; Corbella, Davide; Fazzi, Francesco; Rapido, Francesca; Bonanomi, Ezio

2016-01-01

Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, “developmental hemostasis”, demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the “cell based model of coagulation”, takes into account the interaction between plasma proteins and cells. In the last, the concept of “rebalanced coagulation” highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti-aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations. PMID:26877606

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

PubMed

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests.

PubMed

Prandoni, Paolo; Barbar, Sofia; Milan, Marta; Campello, Elena; Spiezia, Luca; Piovella, Chiara; Pesavento, Raffaele

2015-06-01

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events.

Relation between Intensity of Biocide Practice and Residues of Anticoagulant Rodenticides in Red Foxes (Vulpes vulpes)

PubMed Central

Geduhn, Anke; Jacob, Jens; Schenke, Detlef; Keller, Barbara; Kleinschmidt, Sven; Esther, Alexandra

2015-01-01

Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations for biocidal and plant protection purposes. This can lead to AR exposure of non-target small mammals and their predators, which is known from several regions of the world. However, drivers of exposure variation are usually not known. To identify environmental drivers of AR exposure in non-targets we analyzed 331 liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used local parameters (percentage of urban area and livestock density) to test for associations to residue occurrence. 59.8% of samples collected across Germany contained at least one rodenticide, in 20.2% of cases at levels at which biological effects are suspected. Second generation anticoagulants (mainly brodifacoum and bromadiolone) occurred more often than first generation anticoagulants. Local livestock density and the percentage of urban area were good indicators for AR residue occurrence. There was a positive association between pooled ARs and brodifacoum occurrence with livestock density as well as of pooled ARs, brodifacoum and difenacoum occurrence with the percentage of urban area on administrative district level. Pig holding drove associations of livestock density to AR residue occurrence in foxes. Therefore, risk mitigation strategies should focus on areas of high pig density and on highly urbanized areas to minimize non-target risk. PMID:26418154

Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation.

PubMed

Knight, Stacey; McCubrey, Raymond O; Yuan, Zhong; Woller, Scott C; Horne, Benjamin D; Bunch, T Jared; Le, Viet T; Mills, Roger M; Muhlestein, Joseph B

2016-08-01

Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39- 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03-2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61-4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15-2.49; p < 0.001) compared with angina. In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. © The Author(s), 2016.

Risk of stroke and oral anticoagulant use in atrial fibrillation: a cross-sectional survey

PubMed Central

Holt, Tim A; Hunter, Tina D; Gunnarsson, Candace; Khan, Nada; Cload, Paul; Lip, Gregory YH

2012-01-01

Background Oral anticoagulants substantially reduce the risk of stroke in atrial fibrillation but are underutilised in current practice. Aim To measure the distribution of stroke risk in patients with atrial fibrillation (using the CHADS2 and CHA2DS2-VASc scores) and changes in oral anticoagulant use during 2007–2010. Design and setting Longitudinal series of cross-sectional survey in 583 UK practices linked to the QResearch® database providing 99 351 anonymised electronic records from people with atrial fibrillation. Method The proportion of patients in each CHADS2 and CHA2DS2-VASc risk band in 2010 was calculated; for each of the years 2007–2010, the proportions with risk scores ≥2 that were using anticoagulants or antiplatelet agents were estimated. The proportions identified at high risk were re-estimated using alternative definitions of hypertension based on coded data. Finally, the prevalence of comorbid conditions in treated and untreated high-risk (CHADS2 ≥2) groups was derived. Results The proportion at high risk of stroke in 2010 was 56.9% according to the CHADS2 ≥2 threshold, and 84.5% according to CHA2DS2-VASc ≥2 threshold. The proportions of these groups receiving anticoagulants were 53.0% and 50.7% respectively and increased during 2007–2010. The means of identifying the population of individuals with hypertension significantly influenced the estimated proportion at high risk. Comorbid conditions associated with avoidance of anticoagulants included history of falls, use of nonsteroidal anti-inflammatory drugs, and dementia. Conclusion Oral anticoagulant use in atrial fibrillation has increased in UK practice since 2007, but remains suboptimal. Improved coding of hypertension is required to support systematic identification of individuals at high risk of stroke and could be assisted by practice-based software. PMID:23265231

Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs

PubMed Central

2014-01-01

Background New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. Methods Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell’s viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). Results DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. Conclusions We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery. PMID:24656069

Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

PubMed

Janzic, Andrej; Kos, Mitja

2015-04-01

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

Safety of Endovascular Intervention for Stroke on Therapeutic Anticoagulation: Multicenter Cohort Study and Meta-Analysis.

PubMed

Kurowski, Donna; Jonczak, Karin; Shah, Qaisar; Yaghi, Shadi; Marshall, Randolph S; Ahmad, Haroon; McKinney, James; Torres, Jose; Ishida, Koto; Cucchiara, Brett

2017-05-01

Intravenous (IV) tissue plasminogen activator (tPA) is contraindicated in therapeutically anti-coagulated patients. Such patients may be considered for endovascular intervention. However, there are limited data on its safety. We performed a multicenter retrospective study of patients undergoing endovascular intervention for acute ischemic stroke while on therapeutic anticoagulation. We compared the observed rate of National Institute of Neurological Disorders and Stroke defined symptomatic intracerebral hemorrhage (sICH) with risk-adjusted historical control rates of sICH after IV tPA using weighted averages of the hemorrhage after thrombolysis (HAT) and Multicenter Stroke Survey (MSS) prediction scores. We also performed a metaanalysis of studies assessing risk of sICH with endovascular intervention in patients on anticoagulation. Of 94 cases, mean age was 73 years and median National Institutes of Health Stroke Scale was 19. Anticoagulation consisted of warfarin (n = 51), dabigatran (n = 6), rivaroxaban (n = 13), apixaban (n = 1), IV heparin (n = 19), low molecular weight heparin (n = 3), and combined warfarin and IV heparin (n = 3). sICH was seen in 7 patients (7%, 95% confidence interval 4-15), all on warfarin. Predicted sICH rates for the cohort based on HAT and MSS scoring were 12% and 7%, respectively. Meta-analysis of 6 studies showed no significant difference in sICH between patients undergoing endovascular intervention on anticoagulation and comparator groups. Endovascular intervention in subjects on therapeutic anticoagulation appears reasonably safe, with a sICH rate similar to patients not on anticoagulation receiving IV tPA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation.

PubMed

Camm, A John; Pinto, Fausto J; Hankey, Graeme J; Andreotti, Felicita; Hobbs, F D Richard

2015-07-01

Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

PubMed Central

Jokuszies, Andreas; Herold, Christian; Niederbichler, Andreas D.; Vogt, Peter M.

2012-01-01

Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID:22294976

Specific sulfation and glycosylation—a structural combination for the anticoagulation of marine carbohydrates

PubMed Central

Pomin, Vitor H.; Mourão, Paulo A. S.

2014-01-01

Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs. PMID:24639954

Patient preferences and willingness to pay for different options of anticoagulant therapy.

PubMed

Moia, Marco; Mantovani, Lorenzo Giovanni; Carpenedo, Monica; Scalone, Luciana; Monzini, Mara Silvia; Cesana, Giancarlo; Mannucci, Pier Mannuccio

2013-04-01

New anticoagulant drugs alternative to vitamin K antagonists are currently under clinical evaluation. Patient's preferences should be considered in the development of new therapeutic strategies. Our study aim was to elicit patient preferences, and estimate their willingness to pay for the different treatment options. A Discrete Choice Experiment was administered to patients consecutively attending an anticoagulation clinic, either on stable oral anticoagulant therapy, or during their first visit at the time of starting therapy. Six treatment characteristics were analysed: route and number of medication administrations, frequency of monitoring, risk of some minor bleeding, the amount of attention required for drug/food interactions, requirement for dose adjustment, and out-of-pocket treatment cost. Relationships between patient's preferences and their characteristics were analysed. 255 patients participated (55 % men, with a mean age 64 years; 35.7 % on stable therapy). A statistically significant importance was attributed to all but two characteristics (the amount of attention required for interaction with other drugs/food and for dose adjustment.) Monthly patient willingness to pay was 79 for tablets versus injections; 41 for once-daily versus twice-daily tablets, 25 for drugs without risk of minor bleeding events and 20 for once-monthly versus twice-monthly monitoring. Patients on stable therapy considered more important the amount of attention required for drug/food interactions than did the starters. Younger or working patients considered the reduction of monitoring frequency more important than did the older or not working patients (retired, housewives). This study elicited preferences from patients on oral anticoagulant therapy with a simple and well established method, which allows to obtain information warranted for planning optimal healthcare.

Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice.

PubMed

Beyer-Westendorf, Jan; Camm, A John; Coleman, Craig I; Tamayo, Sally

2016-09-28

Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.

Infrastructure and clinical practice for the detection and management of trauma-associated haemorrhage and coagulopathy.

PubMed

Driessen, A; Schäfer, N; Albrecht, V; Schenk, M; Fröhlich, M; Stürmer, E K; Maegele, M

2015-08-01

Early detection and management of post-traumatic haemorrhage and coagulopathy have been associated with improved outcomes, but local infrastructures, logistics and clinical strategies may differ. To assess local differences in infrastructure, logistics and clinical management of trauma-associated haemorrhage and coagulopathy, we have conducted a web-based survey amongst the delegates to the 15th European Congress of Trauma and Emergency Surgery (ECTES) and the 2nd World Trauma (WT) Congress held in Frankfurt, Germany, 25-27 May 2014. 446/1,540 delegates completed the questionnaire yielding a response rate of 29%. The majority specified to work as consultants/senior physicians (47.3%) in general (36.1%) or trauma/orthopaedic surgery (44.5%) of level I (70%) or level II (19%) trauma centres. Clinical assessment (>80%) and standard coagulation assays (74.6%) are the most frequently used strategies for early detection and monitoring of bleeding trauma patients with coagulopathy. Only 30% of the respondents declared to use extended coagulation assays to better characterise the bleeding and coagulopathy prompted by more individualised treatment concepts. Most trauma centres (69%) have implemented local protocols based on international and national guidelines using conventional blood products, e.g. packed red blood cell concentrates (93.3%), fresh frozen plasma concentrates (93.3%) and platelet concentrates (83%), and antifibrinolytics (100%). 89% considered the continuous intake of anticoagulants including "new oral anticoagulants" and platelet inhibitors as an increasing threat to bleeding trauma patients. This study confirms differences in infrastructure, logistics and clinical practice for the detection and management of trauma-haemorrhage and trauma-associated coagulopathy amongst international centres. Ongoing work will focus on geographical differences.

Anticoagulants and the propagation phase of thrombin generation.

PubMed

Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E; Mann, Kenneth G

2011-01-01

The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may provoke fewer bleeding episodes. More generally, the study shows that computational modeling of the response of core elements of the coagulation proteome to a physiologically relevant tissue factor stimulus may improve the monitoring of a broad range of anticoagulants.

Comparative Transcriptomic Analyses of Three Species of Placobdella (Rhynchobdellida: Glossiphoniidae) Confirms a Single Origin of Blood Feeding in Leeches.

PubMed

Siddall, Mark E; Brugler, Mercer R; Kvist, Sebastian

2016-02-01

One of the recalcitrant questions regarding the evolutionary history of clitellate annelids involves the feeding preference of the common ancestor of extant rhynchobdellid (proboscis bearing) and arhynchobdellid (jaw bearing) leeches. Whereas early evidence, based on morphological data, pointed towards independent acquisitions of blood feeding in the 2 orders, molecular-based phylogenetic data suggest that the ancestor of modern leeches was a sanguivore. Here, we use a comparative transcriptomic approach in order to increase our understanding of the diversity of anticoagulation factors for 3 species of the genus Placobdella, for which comparative data have been lacking, and inspect these in light of archetypal anticoagulant data for both arhynchobdellid and other rhynchobdellid species. Notwithstanding the varying levels of host specificity displayed by the 3 different species of Placobdella, transcriptomic profiles with respect to anticoagulation factors were largely similar -this despite the fact that Placobdella kwetlumye only retains a single pair of salivary glands, as opposed to the 2 pairs more common in the genus. Results show that 9 different anticoagulant proteins and an additional 5 putative antihemostasis proteins are expressed in salivary secretions of the 3 species. In particular, an ortholog of the archetypal, single-copy, anticoagulant hirudin (not previously available as comparative data for rhynchobdellids) is present in at least 2 of 3 species examined, corroborating the notion of a single origin of blood feeding in the ancestral leech.

Algorithms for monitoring warfarin use: Results from Delphi Method.

PubMed

Kano, Eunice Kazue; Borges, Jessica Bassani; Scomparini, Erika Burim; Curi, Ana Paula; Ribeiro, Eliane

2017-10-01

Warfarin stands as the most prescribed oral anticoagulant. New oral anticoagulants have been approved recently; however, their use is limited and the reversibility techniques of the anticoagulation effect are little known. Thus, our study's purpose was to develop algorithms for therapeutic monitoring of patients taking warfarin based on the opinion of physicians who prescribe this medicine in their clinical practice. The development of the algorithm was performed in two stages, namely: (i) literature review and (ii) algorithm evaluation by physicians using a Delphi Method. Based on the articles analyzed, two algorithms were developed: "Recommendations for the use of warfarin in anticoagulation therapy" and "Recommendations for the use of warfarin in anticoagulation therapy: dose adjustment and bleeding control." Later, these algorithms were analyzed by 19 medical doctors that responded to the invitation and agreed to participate in the study. Of these, 16 responded to the first round, 11 to the second and eight to the third round. A 70% consensus or higher was reached for most issues and at least 50% for six questions. We were able to develop algorithms to monitor the use of warfarin by physicians using a Delphi Method. The proposed method is inexpensive and involves the participation of specialists, and it has proved adequate for the intended purpose. Further studies are needed to validate these algorithms, enabling them to be used in clinical practice.

The role of heparin in sepsis: much more than just an anticoagulant.

PubMed

Li, Xu; Ma, Xiaochun

2017-11-01

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

Severe glomerulonephritis complicated by coagulopathy: treatment with anticoaguland and immunosuppresive drugs.

PubMed

Robson, A M; Cole, B R; Kienstra, R A; Kissane, J M; Alkjaersig, N; Fletcher, A P

1977-06-01

Serial determinations, using plasma fibrinogen gel chromatography as well as standard methodology, demonstrated that six children with severe glomerulonephritis, characterized on renal biopsy by glomerular necrosis and crescent formation, had persistent evidence of intravascular coagulation. Based on these observations, therapy with anticoagulants and azathicoagulants and azathioprine was instituted for one year; treatment with anticoagulants was continued for a second year. Anticoagulant therapy was initiated with heparin, followed by oral anticoagulation with phenindione and dipyridamole. In contrast to our earlier experience with similar patients, each of the present patients improved. Urinalyses returned to normal and glomerular filtration rates to near normal values in all patients at the end of the treatment period and have remained so for up to 3.9 years since treatment has been completed. Post-treatment biopsies showed remarkable improvement, with virtually no glomerulosclerosis even in patients who had had a high incidence of glomerular crescents before treatment. It is suggested that the therapeutic regimen favorably influenced the natural history of disease and that plasma fibrinogen chromatographic findings may be helpful in selecting patients likely to benefit from the use of anticoagulant therapy.

Lupus anticoagulants and antiphospholipid antibodies

MedlinePlus

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Antithrombotic Therapy for Atrial Fibrillation

PubMed Central

You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

2012-01-01

Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. PMID:22315271

In situ detection of warfarin using time-correlated single-photon counting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosengren, Annika M.; Karlsson, Bjoern C.G.; Naeslund, Inga

Highlights: {yields} Direct in situ measurement of specific isomeric forms of the anticoagulant warfarin. {yields} TCSPC spectroscopy in conjunction with synthetic Sudlow I binding site receptors. {yields} Development of sensor principle for use in clinical and environmental monitoring. -- Abstract: Here we report on a novel method for the direct in situ measurement of specific isomeric forms of the anticoagulant warfarin using time correlated single-photon counting (TCSPC) spectroscopy in conjunction with synthetic Sudlow I binding site receptors. The method is highly robust over the clinically significant concentration range, and demonstrates the potential of the binding site mimics in conjunction withmore » the spectroscopic strategy employed here for the determination of this important pharmaceutical in clinical or even environmental samples.« less

Lipase-supported metal-organic framework bioreactor catalyzes warfarin synthesis.

PubMed

Liu, Wan-Ling; Yang, Ni-Shin; Chen, Ya-Ting; Lirio, Stephen; Wu, Cheng-You; Lin, Chia-Her; Huang, Hsi-Ya

2015-01-02

A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase-supported metal-organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Current ideas of a complex relationship between atrial fibrillation and ischemic heart disease and of optimum tactics for anticoagulant therapy to prevent embolism in systemic circulation].

PubMed

Golshmid, M V; Gilyarevskiy, S R; Kuzmina, I M; Sinitsina, I I

The article discusses the issue of searching for optimum oral anticoagulants to prevent thrombosis and embolism induced by heart disease both in patients with atrial fibrillation and sinus rhythm. A complex bidirectional relationship between atrial fibrillation and coronary atherosclerosis is considered along with possible mechanisms for development of myocardial infarction in patients with atrial fibrillation. The authors provided evidence-based data which can be used in selecting an anticoagulant for prevention of heart disease induced thrombosis and embolism taking into account both the efficacy and safety established in randomized clinical studies.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

PubMed

Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Dabigatran for the Treatment and Secondary Prevention of Venous Thromboembolism; A Cost-Effectiveness Analysis for the Netherlands.

PubMed

Stevanović, J; de Jong, L A; Kappelhoff, B S; Dvortsin, E P; Voorhaar, M; Postma, M J

2016-01-01

Dabigatran was proven to have similar effect on the prevention of recurrence of venous thromboembolism (VTE) and a lower risk of bleeding compared to vitamin K antagonists (VKA). The aim of this study is to assess the cost-effectiveness (CE) of dabigatran for the treatment and secondary prevention in patients with VTE compared to VKAs in the Dutch setting. Previously published Markov model was modified and updated to assess the CE of dabigatran and VKAs for the treatment and secondary prevention in patients with VTE from a societal perspective in the base-case analysis. The model was populated with efficacy and safety data from major dabigatran trials (i.e. RE-COVER, RECOVER II, RE-MEDY and RE-SONATE), Dutch specific costs, and utilities derived from dabigatran trials or other published literature. Univariate, probabilistic sensitivity and a number of scenario analyses evaluating various decision-analytic settings (e.g. the perspective of analysis, use of anticoagulants only for treatment or only for secondary prevention, or comparison to no treatment) were tested on the incremental cost-effectiveness ratio (ICER). In the base-case scenario, patients on dabigatran gained an additional 0.034 quality adjusted life year (QALY) while saving €1,598. Results of univariate sensitivity analysis were quite robust. The probability that dabigatran is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 98.1%. From the perspective of healthcare provider, extended anticoagulation with dabigatran compared to VKAs was estimated at €2,158 per QALY gained. The ICER for anticoagulation versus no treatment in patients with equipoise risk of recurrent VTE was estimated at €33,379 per QALY gained. Other scenarios showed dabigatran was cost-saving. From a societal perspective, dabigatran is likely to be a cost-effective or even cost-saving strategy for treatment and secondary prevention of VTE compared to VKAs in the Netherlands.

Anticoagulation and high dose liver radiation. A preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lightdale, C.J.; Wasser, J.; Coleman, M.

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes onmore » liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.« less

SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

PubMed

McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

2003-09-18

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

Coagulation management in patients undergoing neurosurgical procedures.

PubMed

Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

2017-10-01

Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

PubMed

DiMarco, John P; Flaker, Gregory; Waldo, Albert L; Corley, Scott D; Greene, H Leon; Safford, Robert E; Rosenfeld, Lynda E; Mitrani, Gladys; Nemeth, Margit

2005-04-01

Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

Management of antithrombotic therapy during cardiac implantable device surgery.

PubMed

AlTurki, Ahmed; Proietti, Riccardo; Birnie, David H; Essebag, Vidal

2016-06-01

Anticoagulants are commonly used drugs that are frequently encountered during device placement. Deciding when to halt or continue the use of anticoagulants is a balance between the risks of thromboembolism versus bleeding. Patients taking warfarin with a high risk of thromboembolism should continue to take their warfarin without interruption during device placement while ensuring their international normalized ratio remains below 3. For patients who are taking warfarin and have low risk of thromboembolism, either interrupted or continued warfarin may be used, with no evidence to clearly support either strategy. There is little evidence to support continuing direct acting oral anticoagulants (DOACs) for device implantation. The timing of halting these medications depends largely on renal function. If bleeding occurs, warfarin׳s anticoagulation effect is reversible with vitamin K and activated prothrombin complex concentrate. There are no DOAC reversal agents currently available, but some are under development. Regarding antiplatelet agents, aspirin alone can be safely continued while clopidogrel alone may also be continued, but with a slightly higher bleeding risk. Dual antiplatelet therapy for bare-metal stent/drug-eluting stent implanted within 4 weeks/6 months, respectively, should be continued due to high risk of stent thrombosis; however, if they are implanted after this period, then clopidogrel can be halted 5 days before the procedure and resumed soon after, while aspirin is continued. If the patient is taking both aspirin and warfarin, aspirin should be halted 5 days prior to the procedure, while warfarin is continued.

Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

PubMed

Wang, Christina Hao; Rubinsky, Anna D; Minichiello, Tracy; Shlipak, Michael G; Price, Erika Leemann

2018-05-31

Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. We compared cystatin C-based eGFR (eGFR cys ) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFR cys ) and eGFRs using three creatinine-based equations: CKD-EPI (eGFR EPI ), Modified Diet in Renal Disease (eGFR MDRD ), and Cockcroft-Gault (eGFR CG ). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of - 7.1 (IQR - 17.2, 2.6) mL/min/1.73 m 2 versus eGFR EPI , - 21.2 (IQR - 43.7, - 8.1) mL/min/1.73 m 2 versus eGFR MDRD , and - 25.9 (IQR - 46.8, - 8.7) mL/min/1.73 m 2 versus eGFR CG . Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further investigation is needed to confirm these findings and evaluate implications for bleeding and other clinical outcomes. Not applicable.

[Drug compliance of patients on anticoagulant treatment].

PubMed

Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula

2015-08-09

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

The first pharmacist-managed anticoagulation clinic under a collaborative practice agreement in Qatar: clinical and patient-oriented outcomes.

PubMed

Elewa, H F; AbdelSamad, O; Elmubark, A E; Al-Taweel, H M; Mohamed, A; Kheir, N; Mohamed Ibrahim, M I; Awaisu, A

2016-08-01

Optimal outpatient anticoagulation management requires a systematic and coordinated approach. Extensive evidence regarding the benefits of pharmacist-managed anticoagulation services has been reported in the literature. The quality and outcomes associated with pharmacist-managed anticoagulation clinics under collaborative practice agreements in the Middle East have rarely been reported. The first pharmacist-managed ambulatory anticoagulation clinic in Qatar was launched at Al-Wakrah Hospital in March 2013. The objectives of this study were to: (i) describe the practice model of the clinic, (ii) evaluate the quality of the clinic [i.e. the time in therapeutic range (TTR)] and the clinical outcomes (i.e. the efficacy and safety), and (iii) determine the patients' satisfaction and overall quality of life (QoL). Clinical outcome data were collected through a retrospective chart review of all patients managed from March 2013 to October 2014 at the pharmacist-managed anticoagulation clinic. Furthermore, the patient-oriented outcomes data were prospectively collected using the 24-item Duke Anticoagulation Satisfaction Scale (DASS). Each item was assessed using a 7-point Likert-type scale on which lower scores indicated better QoL and greater satisfaction. The clinical outcome data analyses included 119 patients who were enrolled at the clinic during the 19-month study period. The mean number of international normalized ratio (INR) tests/month was 65 ± 9, the average testing frequency was 2·7 ± 1·6 weeks, and the average %TTR was 76·8 ± 22·9%. There was one major bleeding event (0·67%/year), 12 minor bleeding events (8%/year) and two thromboembolic events (1·35%/year) recorded during the study period. Of the 119 patients, 50 participated in the satisfaction and QoL survey. The median (IQR) total QoL score of these subjects was 63 (48) (minimum-maximum achievable score: 24-168). Seventy-six per cent of the patients indicated 'a lot to very much' in terms of their overall satisfaction with the anticoagulation treatment. The participants who were naïve to anticoagulation treatment reported a significantly greater satisfaction and better QoL than the experienced patients [58 (44) vs. 82 (59); P = 0·009]. These findings provide early evidence that the patients who were managed at a pharmacy-based anticoagulation clinic in an evolving healthcare system experienced optimal anticoagulation management. © 2016 John Wiley & Sons Ltd.

PORTALS: design of an innovative approach to anticoagulation management through eHealth.

PubMed

Talboom-Kamp, E P W A; Verdijk, N A; Talboom, I J S H; Harmans, L M; Numans, M E; Chavannes, N H

2017-03-16

For the monitoring of International Normalized Ratio (INR) values, venous thromboembolism (VTE) and atrial fibrillation (AF) patients can visit anticoagulation clinics, laboratories, or physicians for venous puncture. Point-of-care testing (POCT) made it possible for patients to monitor INR themselves (self-monitoring) and even self-adjust their medication dosage (self-dosage). Both skills are accepted as forms of self-management. eHealth applications can improve this self-management, resulting in better clinical outcomes. Our study, called PORTALS, aims at identifying the optimal implementation strategy of training to improve self-management and explore factors that enhance good self-management skills. In addition, the relationship between the implementation strategy of training, clinical outcomes, and individual characteristics will be investigated. Of the 247 recruited participants, 110 chose to continue with regular care. 137 patients have been randomly divided in subgroups and compared using a parallel cohort design: one group will be trained and educated by e-learning, and the other group will receive face-to-face group training. More insight in factors that enhance good self-management will help to improve clinical outcomes and patient satisfaction on anticoagulation therapy. Our study will provide practical insights and knowledge of eHealth in daily practice and of the importance of education on the adoption of self-management. We expect the self-management program including training to help patients to better manage their own INR values and medication use, thereby increasing health status and diminishing thromboembolic events and hospitalisation. The Netherlands National Trial Register, number NTR3947 .

Oral Anticoagulation in Chronic Kidney Disease and Atrial Fibrillation.

PubMed

Heine, Gunnar H; Brandenburg, Vincent; Schirmer, Stephan H

2018-04-27

Cardiological societies recommend, in their guidelines, that patients with atrial fibrillation and an intermediate (or higher) risk of stroke and systemic embolization should be treated with oral anticoagulant drugs. For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA) for this purpose. It is unclear, however, whether patients with chronic kidney disease and atrial fibrillation benefit from oral anticoagulation to the same extent as those with normal kidney function. It is also unclear which of the two types of anti - coagulant drug is preferable for patients with chronic kidney disease; NOAC are, in part, renally eliminated. This review is based on pertinent publications retrieved by a selective literature search, and on international guidelines. Current evidence suggests that patients with atrial fibrillation who have chronic kidney disease with a glomerular filtration rate (GFR) above 15 mL/ min/1.73 m² should be treated with an oral anticoagulant drug if they have an at least intermediate risk of embolization, as assessed with the CHA2DS2-VASc score. For patients with advanced chronic kidney disease (GFR from 15 to 29 mL/ min/1.73 m²), however, this recommendation is based only on registry studies. For dialysis patients with atrial fibrillation, decisions whether to give oral anticoagulant drugs should be taken on an individual basis, in view of the elevated risk of hemorrhage and the unclear efficacy of such drugs in these patients. The subgroup analyses of the NOAC approval studies show that, for patients with atrial fibrillation and chronic kidney disease with a creatinine clearance of >25-30 mL/min, NOAC should be given in preference to VKA, as long as the patient does not have mitral valve stenosis or a mechanical valve prosthesis. For those whose creatinine clearance is less than 25 mL/min, the relative merits of NOAC versus VKA are still debated. The cardiological societies' recommendation that patients with atrial fibrillation should be given oral anticoagulant drugs applies to the majority of such patients who also have chronic kidney disease.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

PubMed

Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

2016-01-01

Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the combination of ASA, oral anticoagulant, and P2Y12 inhibitor was used for 54% (38/70) of the patients. Fewer than half of the patients in this study received TAT, and almost 20% received non-evidence-based therapy with a direct-acting oral anticoagulant or ticagrelor, alone or in combination. Despite current guideline recommendations, the rate of TAT utilization was lower than rates reported in the literature.

International normalized ratio self-management lowers the risk of thromboembolic events after prosthetic heart valve replacement.

PubMed

Eitz, Thomas; Schenk, Soren; Fritzsche, Dirk; Bairaktaris, Andreas; Wagner, Otto; Koertke, Heinrich; Koerfer, Reiner

2008-03-01

Although prosthetic valves are durable and easy to implant, the need for lifetime warfarin-based anticoagulation restricts their exclusive usage. We investigated if anticoagulation self-management improves outcome in a single-center series. Between 1994 and 1998, 765 patients with prosthetic valve replacements were prospectively enrolled and randomized to receive conventional anticoagulation management by their primary physician (group 1, n = 295) or to pursue anticoagulation self-management (group 2, n = 470). A study head office was implemented to coordinate and monitor anticoagulation protocols, international normalized ratios (INR), and adverse events. Patients were instructed on how to obtain and test their own blood samples and to adjust warfarin dosages according to the measured INR (target range, 2.5 to 4). Mean INR values were slightly yet significantly smaller in group 1 than in group 2 (2.8 +/- 0.7 vs 3.0 +/- .6, p < 0.001). Moreover, INR values of patients with conventional INR management were frequently measured outside the INR target range, whereas those with anticoagulation self-management mostly remained within the range (35% vs 21%, p < 0.001). In addition, the scatter of INR values was smaller if self-managed. Freedom from thromboembolism at 3, 12, and 24 months, respectively, was 99%, 95%, and 91% in group 1 compared with 99%, 98%, and 96% in group 2 (p = 0.008). Bleeding events were similar in both groups. Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome. Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events. Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up.

APOLLO I: Anticoagulation control in atrial fibrillation.

PubMed

Pinho-Costa, Luís; Moreira, Sónia; Azevedo, Cristiana; Azevedo, Pedro; Castro, Elisabete; Sousa, Hélder; Melo, Miguel

2015-05-01

Anticoagulation control as assessed by time in therapeutic range (TTR) correlates positively with the safety and efficacy of thromboprophylaxis in atrial fibrillation. We set out to assess TTR in our unit and to investigate determinants of better control. This was a case series study of atrial fibrillation patients anticoagulated with warfarin or acenocoumarol at the Family Health Unit of Fânzeres. Sociodemographic and clinical data were collected and TTR was calculated by the Rosendaal method, based on international normalized ratio tests performed in external laboratories in the preceding six months. SPSS 21.0 was used for the statistical analysis, with descriptive statistics, Spearman's correlation, and the Mann-Whitney U and Kruskal-Wallis tests. Of the 106 eligible patients, 70% participated in the study. Median TTR was 65.3% (P25=48.3%, P75=86.8%). We found a positive association between this variable and duration of atrial fibrillation (ρ=0.477, p<0.001, r(2)=0.116) and with duration of anticoagulation (ρ=0.5, p<0.001, r(2)=0.087). No association was found with age, gender, educational level or existence of a caregiver (p>0.05). Median TTR in our unit is similar to that in southern European countries and close to the good control threshold (70%) proposed by the European Society of Cardiology. The duration of atrial fibrillation and of anticoagulation explains only a small part of the measure's variability. Other determinants of anticoagulation control must be investigated in future studies and comparative studies should be carried out in family health units monitoring anticoagulation on the premises. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

PubMed

Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

2017-07-01

Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gastrointestinal Bleeding.

PubMed

Nable, Jose V; Graham, Autumn C

2016-05-01

Acute gastrointestinal bleeding is a commonly encountered chief complaint with a high morbidity and mortality. The emergency physician is challenged with prompt diagnosis, accurate risk assessment, and appropriate resuscitation of patients with gastrointestinal bleeding. Goals of care aim to prevent end-organ injury, manage comorbid illnesses, identify the source of bleeding, stop continued bleeding, support oxygen carrying capacity, and prevent rebleeding. This article reviews current strategies for risk stratification, diagnostic modalities, localization of bleeding, transfusion strategies, adjunct therapies, and reversal of anticoagulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Intravenous heparin dosing strategy in hospitalized patients with atrial dysrhythmias.

PubMed

Roswell, Robert O; Greet, Brian; Shah, Sunny; Bernard, Samuel; Milin, Alexandra; Lobach, Iryna; Guo, Yu; Radford, Martha J; Berger, Jeffrey S

2016-08-01

Patients with non-valvular atrial fibrillation (AF) have an elevated stroke risk that is 2-7 times greater than in those without AF. Intravenous unfractionated heparin (UFH) is commonly used for hospitalized patients with atrial fibrillation and atrial flutter (AFL) to prevent stroke. Dosing strategies exist for intravenous anticoagulation in patients with acute coronary syndromes and venous thromboembolic diseases, but there are no data to guide providers on a dosing strategy for intravenous anticoagulation in patients with AF/AFL. 996 hospitalized patients with AF/AFL on UFH were evaluated. Bolus dosing and initial infusion rates of UFH were recorded along with rates of stroke, thromboemobolic events, and bleeding events as defined by the International Society on Thrombosis and Haemostasis criteria. Among 226 patients included in the analysis, 76 bleeding events occurred. Using linear regression analysis, initial rates of heparin infusion ranging from 9.7 to 11.8 units/kilogram/hour (U/kg/h) resulted in activated partial thromboplastin times that were within therapeutic range. The median initial infusion rate in patients with bleeding was 13.3 U/kg/h, while in those without bleeding it was 11.4 U/kg/h; p = 0.012. An initial infusion rate >11.0 U/kg/h yielded an OR 1.95 (1.06-3.59); p = 0.03 for any bleeding event. Using IV heparin boluses neither increased the probability of attaining a therapeutic aPTT (56.1 vs 56.3 %; p = 0.99) nor did it significantly increase bleeding events in the study (35.7 vs 31.3 %; p = 0.48). The results suggest that higher initial rates of heparin are associated with increased bleeding risk. From this dataset, initial heparin infusion rates of 9.7-11.0 U/kg/h without a bolus can result in therapeutic levels of anticoagulation in hospitalized patients with AF/AFL without increasing the risk of bleeding.

Screening cleavage of Factor XIII V34X Activation Peptides by thrombin mutants: A strategy for controlling fibrin architecture.

PubMed

Jadhav, Madhavi A; Goldsberry, Whitney N; Zink, Sara E; Lamb, Kelsey N; Simmons, Katelyn E; Riposo, Carmela M; Anokhin, Boris A; Maurer, Muriel C

2017-10-01

In blood coagulation, thrombin converts fibrinogen into fibrin monomers that polymerize into a clot network. Thrombin also activates Factor XIII by cleaving the R37-G38 peptide bond of the Activation Peptide (AP) segment. The resultant transglutaminase introduces covalent crosslinks into the fibrin clot. A strategy to modify clot architecture would be to design FXIII AP sequences that are easier or more difficult to be thrombin-cleaved thus controlling initiation of crosslinking. To aid in this design process, FXIII V34X (28-41) Activation Peptides were kinetically ranked for cleavage by wild-type thrombin and several anticoagulant mutants. Thrombin-catalyzed hydrolysis of aromatic FXIII F34, W34, and Y34 APs was compared with V34 and L34. Cardioprotective FXIII L34 remained the variant most readily cleaved by wild-type thrombin. The potent anticoagulant thrombins W215A and W215A/E217A (missing a key substrate platform for binding fibrinogen) were best able to hydrolyze FXIII F34 and W34 APs. Thrombin I174A and L99A could effectively accommodate FXIII W34 and Y34 APs yielding kinetic parameters comparable to FXIII AP L34 with wild-type thrombin. None of the aromatic FXIII V34X APs could be hydrolyzed by thrombin Y60aA. FXIII F34 and W34 are promising candidates for FXIII - anticoagulant thrombin systems that could permit FXIII-catalyzed crosslinking in the presence of reduced fibrin formation. By contrast, FXIII Y34 with thrombin (Y60aA or W215A/E217A) could help assure that both fibrin clot formation and protein crosslinking are hindered. Regulating the activation of FXIII is predicted to be a strategy for helping to control fibrin clot architecture and its neighboring environments. Copyright © 2017 Elsevier B.V. All rights reserved.

Current and Emerging Uses of Insertable Cardiac Monitors: Evaluation of Syncope and Monitoring for Atrial Fibrillation.

PubMed

Tomson, Todd T; Passman, Rod

Insertable cardiac monitors (ICMs) have provided clinicians with a superb tool for assessing infrequent or potentially asymptomatic arrhythmias. ICMs have shown their usefulness in the evaluation of unexplained syncope, providing high diagnostic yields in a cost-effective manner. While unexplained syncope continues to be the most common reason for their use, ICMs are increasingly being used for the monitoring of atrial fibrillation (AF). Recent trials have demonstrated that a substantial proportion of patients with cryptogenic stroke have AF detected only by the prolonged monitoring provided by ICMs. A particularly promising and emerging use for ICMs is in the management of anticoagulation in patients with known paroxysmal AF. The introduction in recent years of ICMs with automatic AF detection algorithms and continuous remote monitoring in combination with novel oral anticoagulants have opened the door for targeted anticoagulation guided by remote monitoring, a strategy that has recently shown promise in pilot studies of this technique. While further research is needed before official recommendations can be given, this use of ICMs opens exciting new possibilities for personalized medicine that could potentially reduce bleeding risk and improve quality of life in patients with atrial fibrillation.

Influence of novel oral anticoagulants on anticoagulation care management.

PubMed

Janzic, Andrej; Kos, Mitja

2017-09-01

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

PubMed

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

PubMed Central

2012-01-01

Introduction The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Results Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure. PMID:22305273

Hemodialysis Tunneled Catheter Noninfectious Complications

PubMed Central

Miller, Lisa M.; MacRae, Jennifer M.; Kiaii, Mercedeh; Clark, Edward; Dipchand, Christine; Kappel, Joanne; Lok, Charmaine; Luscombe, Rick; Moist, Louise; Oliver, Matthew; Pike, Pamela; Hiremath, Swapnil

2016-01-01

Noninfectious hemodialysis catheter complications include catheter dysfunction, catheter-related thrombus, and central vein stenosis. The definitions, causes, and treatment strategies for catheter dysfunction are reviewed below. Catheter-related thrombus is a less common but serious complication of catheters, requiring catheter removal and systemic anticoagulation. In addition, the risk factors, clinical manifestation, and treatment options for central vein stenosis are outlined. PMID:28270922

Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

PubMed

Singer, Daniel E; Albers, Gregory W; Dalen, James E; Fang, Margaret C; Go, Alan S; Halperin, Jonathan L; Lip, Gregory Y H; Manning, Warren J

2008-06-01

This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age < or =75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of > or =48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

PubMed Central

Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

2015-01-01

Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively. Interpretation: We observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty. PMID:26770966

Dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan.

PubMed

Wang, Jianglin; Hu, Wei; Liu, Qun; Zhang, Shengmin

2011-07-01

Heparinized biomaterials exhibit great anticoagulant properties. However, they promote proliferation of Staphylococcus aureus (S. aureus) and therefore cause infection within the bloodstream upon implantation in vivo. In the present study, an interesting dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan was synthesized. First, heparin was grafted onto the silk fibroin by covalent immobilization with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). All data gathered from Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and elemental analysis (EA) indicated that the heparin was successfully immobilized onto the silk fibroin. The dual-functional composite of heparinized silk fibroin and chitosan was then fabricated by a blending method. The anticoagulant activity of the heparinized materials was evaluated using the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). The results showed that both heparinized silk fibroin and the composite material exhibited better hemocompatibility in comparison with single silk fibroin or chitosan. The antibacterial property of the materials was investigated by the pour-plate method. Results further suggested that the composite antibacterial property with respect to S. aureus was significantly enhanced. The dual-functionality of the composite material may supply a potential choice in blood contact devices. Copyright © 2011 Elsevier B.V. All rights reserved.

The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories.

PubMed

Podda, Gian Marco; Pugliano, Mariateresa; Femia, Eti Alessandra; Mezzasoma, Anna Maria; Gresele, Paolo; Carpani, Giovanni; Cattaneo, Marco

2012-07-01

Spuriously low platelet counts (PCs) can be observed in normal blood samples anticoagulated with ethylenediamine tetra-acetic acid (EDTA)and, much less frequently, with citrate-tris-pyridossalphosphate (CPT),due to time-dependent in vitro platelet agglutination. Accuracy in PC determination is essential as PC is one of the parameters that usually guides treatment for thrombocytopenic patients. PCs of 93 thrombocy to penic patients were measured in EDTA- or CPT-anticoagulated blood samples immediately after sampling (t0) and 90 min (t90) after storage at room temperature. The presence of platelet agglutinates in blood samples was determined by examining blood smears using optical microscopy.PCs decreased at t90 with both anticoagulants. Platelet agglutinates were present at t90 in 27% of EDTA-samples vs. 2% of CPT-samples with decreased PCs (P < 0.001). Based on PCs in EDTA-samples, 15 patients (16%) shifted from a lower bleeding risk at t0 to a higher bleeding risk category at t90 (P 5 0.019), compared to 5 (5%) patients, based on PCs in CPT-samples. Therefore, time-dependent in vitro platelet agglutination in EDTA-blood samples may cause underestimation of PCs in thrombocytopenic patients, possibly leading to improper management.

Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A.

PubMed

Ku, Sae-Kwang; Bae, Jong-Sup

2014-03-01

Withaferin A (WFA), an active compound from Withania somnifera, is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. However, antiplatelet, anticoagulant, and profibrinolytic properties of WFA have not been studied. In this study, the anticoagulant activities of WFA were measured by monitoring activated partial thromboplastin-time (aPTT), prothrombin time (PT), fibrin polymerization, platelet aggregation, thrombus formation, and the activities of cell-based thrombin and activated factor X (FXa). The effects of WFA on the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were also tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Our data showed that WFA inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation, FeCl3-induced thrombus formation, prolonged aPTT and PT significantly and inhibited the activities and production of thrombin and FXa. WFA prolonged in vivo and ex vivo bleeding time and inhibited TNF-α induced PAI-1 production. Furthermore, PAI-1/t-PA ratio was significantly decreased by WFA. Collectively, these results indicate that WFA possesses antithrombotic activities and suggest that the current study could provide bases for the development of new anticoagulant agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Proposed Criteria for the Use of Low-Dose Vitamin K Supplementation in Patients Using Vitamin K Antagonists: A Literature Review of a Clinical Controversy.

PubMed

Evans, Christy E; Getchell, Katerine E; Ivy, Delaney R

2018-04-01

Vitamin K antagonists (VKAs) have been used for decades to prevent thromboembolic events, but can be burdensome to patients based on numerous factors impacting anticoagulation control. Low-dose vitamin K supplementation has been theorized to improve anticoagulation control in patients on VKAs that may be vitamin K deficient. The objective of this literature review is to propose criteria for implementing low-dose vitamin K supplementation in patients on VKAs. The CHEST 2012 antithrombotic guidelines recommended against routine use of vitamin K supplementation in patients on VKAs. An observational study and three randomized controlled trials pertaining to this recommendation were evaluated. A literature review was also performed on other studies looking at the impact of low-dose vitamin K supplementation on anticoagulation control through a search in PubMed and the Cochrane Database of Systematic Reviews. One retrospective and two prospective studies were reviewed. Six of the seven studies demonstrated a non-statistically significant trend in data supporting improvement in anticoagulation control with low-dose vitamin K supplementation. While many of the studies did not achieve significant results, the majority demonstrated a trend in support of the improvement of anticoagulation control with low-dose vitamin K supplementation in patients on VKAs.

Management of venous thromboembolism in patients with glioma.

PubMed

Al Megren, Mosaad; De Wit, Carine; Al Qahtani, Mohammad; Le Gal, Grégoire; Carrier, Marc

2017-08-01

Venous thromboembolism (VTE) is a common complication among patients with glioma. However, data on the safety of therapeutic doses of anticoagulation is scarce in this patient population. The purpose of this study is to evaluate the risk of intracranial hemorrhage (ICH) in glioma patients receiving therapeutic anticoagulation for VTE treatment. We conducted a case-control study including glioma patients with and without acute VTE from Jan 2010 to March 2015. Controls were matched based on age, gender and tumor grade. 569 patients with glioma were identified, 76 (13.3%) developed acute VTE. Of the 70 patients treated with full dose anticoagulant therapy, 14 (20%) patients had a major bleeding including 11 (15.7%) ICH. The odds ratio for ICH in patients with glioma and VTE who were treated with anticoagulation compared to the control group was 7.5 (95% CI, 1.6-34.9) p=0.01. Overall survival was similar for VTE and control group (36 vs. 42months, p=0.93). Therapeutic anticoagulation is associated with a 7-fold increase risk of ICH in glioma patients. Data emerging from this study support the need for high quality studies to evaluate the risk of ICH in patients with glioma and VTE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Practical management of anticoagulation in patients with atrial fibrillation.

PubMed

Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

2015-04-07

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study.

PubMed

Klok, Frederikus A; Ageno, Walter; Barco, Stefano; Binder, Harald; Brenner, Benjamin; Duerschmied, Daniel; Empen, Klaus; Faggiano, Pompilio; Ficker, Joachim H; Galiè, Nazzareno; Ghuysen, Alexandre; Held, Matthias; Heydenreich, Nadine; Huisman, Menno V; Jiménez, David; Kozak, Matija; Lang, Irene M; Lankeit, Mareike; Münzel, Thomas; Petris, Antoniu; Pruszczyk, Piotr; Quitzau, Kurt; Schellong, Sebastian; Schmidt, Kai-Helge; Stefanovic, Branislav S; Verschuren, Franck; Wolf-Puetz, Anamaria; Meyer, Guy; Konstantinides, Stavros V

2017-12-01

Patients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

Adalimumab-based treatment versus DMARDs for venous thrombosis in Behçet syndrome. A retrospective study of 70 patients with vascular involvement.

PubMed

Emmi, Giacomo; Vitale, Antonio; Silvestri, Elena; Boddi, Maria; Becatti, Matteo; Fiorillo, Claudia; Fabiani, Claudia; Frediani, Bruno; Emmi, Lorenzo; Scala, Gerardo Di; Goldoni, Matteo; Bettiol, Alessandra; Vaglio, Augusto; Cantarini, Luca; Prisco, Domenico

2018-04-20

Since Behçet syndrome (BS) is the prototype of inflammation-induced thrombosis, immunosuppressants are recommended in place of anticoagulants. Here we assessed the clinical efficacy and the corticosteroid-sparing effect of adalimumab (ADA)-based treatment versus DMARDs in a large retrospective cohort of patients with BS-related venous thrombosis. We retrospectively collected data from 70 BS patients treated with DMARDs or ADA-based regimens (ADA ± DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA-based regimens and DMARDs, with respect to efficacy, corticosteroid-sparing role and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. After a mean follow-up of 25.7±23.2 months, ADA-based regimens induced clinical and instrumental improvement of venous thrombosis more frequently (p=0.001) and rapidly (p<0.0001) than DMARDs. The mean dose of corticosteroids administered at the last follow-up was significantly lower in the ADA-based regimens than in the DMARDs one (p<0.0001). The time on treatment was significantly longer in ADA-based regimens than in the DMARDs one (p=0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA-based regimens among subjects receiving anticoagulants and those who did not. In this large retrospective study we have shown that ADA-based regimen is more effective and rapid in inducing resolution of venous thrombosis in BS patients than DMARDs, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy on venous complications of either ADA-based regimens or DMARDs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anticoagulant Medicine: Potential for Drug-Food Interactions

MedlinePlus

... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...

Regional citrate anticoagulation in hemodialysis: an observational study of safety, efficacy, and effect on calcium balance during routine care.

PubMed

Singer, Richard F; Williams, Oliver; Mercado, Chari; Chen, Bonny; Talaulikar, Girish; Walters, Giles; Roberts, Darren M

2016-01-01

Regional citrate hemodialysis anticoagulation is used when heparin is contraindicated, but most protocols require large infusions of calcium and frequent intradialytic plasma ionized calcium measurements. The objective of this study was to determine the safety, efficacy, and effect on calcium balance of regional citrate anticoagulation using sparse plasma ionized calcium sampling. The design of this study was observational. The setting of this study was the hospital hemodialysis center. The subjects of this study were the hospital hemodialysis patients. Dialysate calcium concentration by atomic absorption spectroscopy and total dialysate weight were used as measurements. Regional citrate anticoagulation was introduced using zero calcium dialysate, pre-dialyzer citrate infusion, and post-dialyzer calcium infusion. Infusions were adjusted based on pre- and post-dialyzer calcium measurements obtained at least twice during a 4-h dialysis. The protocol was simplified after the first 357 sessions to dispense with post-dialyzer calcium measurements. Heparin-anticoagulated sessions were performed using acetate-acidified 1.25 mmol/L calcium or citrate-acidified 1.5 mmol/L calcium dialysate. Calcium balance assessment was by complete dialysate recovery. Safety and efficacy were assessed prospectively using a point-of-care database to record ionized calcium and clinical events. Groups were compared using t test, ANOVA, Wilcoxon rank sum, or Kruskal-Wallis as appropriate. Seventy-five patients received regional citrate-anticoagulated dialysis over 1051 dialysis sessions. Of these, 357 dialysis sessions were performed using the original citrate anticoagulation protocol and 694 using the simplified protocol. Dialysis was effective and safe. Only 3 dialyzers clotted; 1 patient suffered symptomatic hypercalcemia and none suffered symptomatic hypocalcemia. Calcium balance was assessed in 15 regional citrate-anticoagulated dialysis sessions and 30 heparin-anticoagulated sessions. The median calcium loss was 0.8 mmol/h dialyzed in both groups (p = 0.43), and end of treatment ionized calcium was the same in both groups (1.07 ± 0.04 mmol/L). Our findings for calcium balance, efficacy, and safety are valid only for the protocol studied, which excluded patient with severe liver dysfunction. Regional citrate dialysis can be performed safely and effectively using a sparse plasma calcium sampling protocol. The calcium balance induced by this protocol is not different to that seen in standard heparin-anticoagulated dialysis, but in the absence of prospective studies, it is unknown whether this is optimal for patient care.

Effect of chronic kidney disease on warfarin management in a pharmacist-managed anticoagulation clinic.

PubMed

Kleinow, Megan E; Garwood, Candice L; Clemente, Jennifer L; Whittaker, Peter

2011-09-01

There is growing evidence that kidney disease affects hepatically cleared drugs. Accordingly, we hypothesized that chronic kidney disease (CKD) would disrupt anticoagulation of warfarin-treated patients and thereby increase the amount of management required to maintain appropriate anticoagulation. Specifically, we anticipated that more dose manipulations (both dose changes and transient dose adjustments) and shorter times between scheduled clinic visits would be required for anticoagulation patients with CKD. To determine how CKD affected warfarin maintenance dose, anticoagulation stability, the proportion of clinic visits that necessitated a dose manipulation (either a change in the prescribed weekly dose or a transient dose adjustment), and the length of time between scheduled visits in 2 pharmacist-managed anticoagulation clinics. Our retrospective, cohort chart review investigated warfarin response in anticoagulation clinic patients. From the clinic database of patients with an international normalized ratio (INR) target range of 2.0-3.0, we matched 20 of 24 patients with CKD (estimated creatinine clearance less than 60 mL per minute) to 20 comparison group patients (estimated creatinine clearance greater than 60 mL per minute) based on parameters demonstrated to affect warfarin dose: ethnicity, gender, age, body surface area, and simvastatin use. We calculated the average weekly dose used to maintain target INR (assessment period range=116-1,408 days). To evaluate anticoagulation stability and patient management, we quantified several parameters, including the percentage of total time in therapeutic range, the proportion of clinic visits that required a dose change, and the time between scheduled visits. We compared group means using t-tests, and categorical data were compared using Fisher's exact test. Our population was predominantly female (75%) and of African ancestry (95%); average age 60 years. Patients with CKD required a 24% lower dose than the comparison group (mean [SD]=35.9 [10.7] vs. 47.0 [11.2] mg per week, P=0.003) and spent less time in therapeutic range required increased clinic management versus the comparison group, as indicated by a significantly higher proportion of clinic visits at which dose changes occurred (22% vs. 12%, P<0.001) and a decreased time between scheduled visits (mean [SD] of 16.0 [3.2] days vs. 19.7 [3.4] days, respectively, P=0.001). CKD was associated with both decreased warfarin maintenance dose and decreased anticoagulation stability which, in turn, required more frequent and intensive anticoagulation clinic management.

Pharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon

PubMed Central

Verhoef, Talitha I; Redekop, William K; Daly, Ann K; van Schie, Rianne M F; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

2014-01-01

Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose–response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials. PMID:23919835

[Recent and upcoming randomized trials for left atrial appendage occlusion : Need for a definite assessment of the situation].

PubMed

Skurk, Carsten; Hartung, Johannes Jakob; Landmesser, Ulf

2017-12-01

Atrial fibrillation (AF) is the most common arrhythmia affecting more than 1.6 million patients in Germany. Based on demographic developments, an the number is expected to increase. Embolic strokes in AF patients are particularly severe, and individualized new oral anticoagulant (NOAC) therapy reduces the incidence of stroke in these patients by approximately 70%. Besides vitamin K antagonists, the NOACs rivaroxaban, dabigatran, apixaban, and edoxaban have been introduced into clinical practice; however, major bleeding still occurs at a rate of 2-3% per year. Moreover, randomized studies and real-life registries suggest that >20% of patients with AF and an indication for anticoagulation cannot tolerate chronic oral anticoagulant therapy. Therefore, an alternative method for stroke prevention in AF patients has been developed, i. e., catheter-based exclusion of the left atrial appendage (LAA), a location that is prone for thrombus formation in these patients. The randomized trials of catheter-based LAA occlusion have compared this interventional therapy with vitamin K antagonists. In the future, however, LAA exclusion needs to be compared with NOAC therapy. Moreover, percutaneous LAA exclusion in clinical practice is mostly offered to patients ineligible for long-term oral anticoagulation or with high bleeding risk. However, no controlled, randomized trial data exist for this patient population. These data are needed for appropriate clinical judgment and optimal clinical management. Ongoing studies and scientific questions that are important to define the future for catheter-based LAA closure are discussed in this review.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

PubMed

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

PubMed Central

Cogneau, Joël; Gaboreau, Yoann; Abenhaïm, Nathan; Bayen, Marc; Calafiore, Matthieu; Guichard, Claude; Jacquet, Jean-Pierre; Lacoin, François; Bertoletti, Laurent

2017-01-01

Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777 PMID:28384199

Diet as prophylaxis and treatment for venous thromboembolism?

PubMed Central

2010-01-01

Background Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored. Methods and Findings The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial. Conclusions Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials. PMID:20701748

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

PubMed

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient setting before admission. Our findings support the current literature, indicating that many patients with AF are not receiving appropriate thromboprophylaxis to counter their risk for stroke. Increased use of appropriate anticoagulation, particularly in high-risk patients, has the potential to reduce the incidence of stroke along with associated fatalities and morbidities.

Treatment of pregnancy-associated venous thromboembolism - position paper from the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH).

PubMed

Linnemann, Birgit; Scholz, Ute; Rott, Hannelore; Halimeh, Susan; Zotz, Rainer; Gerhardt, Andrea; Toth, Bettina; Bauersachs, Rupert

2016-01-01

Venous thromboembolism (VTE) is a major cause of maternal morbidity during pregnancy and the postpartum period. However, because there is a lack of adequate study data, management strategies for pregnancy-associated VTE must be deduced from observational stu-dies and extrapolated from recommendations for non-pregnant patients. In this review, the members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH) have summarised the evidence that is currently available in the literature to provide a practical approach for treating pregnancy-associated VTE. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparin (LMWH) is the anticoagulant treatment of choice in cases of acute VTE during pregnancy. No differences between once and twice daily LMWH dosing regimens have been reported, but twice daily dosing seems to be advisable, at least peripartally. It remains unclear whether determining dose adjustments according to factor Xa activities during pregnancy provides any benefit. Management of delivery deserves attention and mainly depends on the time interval between the diagnosis of VTE and the expected delivery date. In particular, if VTE manifests at term, delivery should be attended by an experienced multidisciplinary team. In lactating women, an overlapping switch from LMWH to warfarin is possible. Anticoagulation should be continued for at least 6 weeks postpartum or for a minimum period of 3 months. Although recommendations are provided for the treatment of pregnancy-associated VTE, there is an urgent need for well-designed prospective studies that compare different management strategies and define the optimal duration and intensity of anticoagulant treatment.

Immunoassay and antibody microarray analysis of the HUPO Plasma Proteome Project reference specimens: Systematic variation between sample types and calibration of mass spectrometry data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haab, Brian B.; Geierstanger, Bernhard H.; Michailidis, George

2005-08-01

Four different immunoassay and antibody microarray methods performed at four different sites were used to measure the levels of a broad range of proteins (N = 323 assays; 39, 88, 168, and 28 assays at the respective sites; 237 unique analytes) in the human serum and plasma reference specimens distributed by the Plasma Proteome Project (PPP) of the HUPO. The methods provided a means to (1) assess the level of systematic variation in protein abundances associated with blood preparation methods (serum, citrate-anticoagulated-plasma, EDTA-anticoagulated-plasma, or heparin-anticoagulated-plasma) and (2) evaluate the dependence on concentration of MS-based protein identifications from data sets usingmore » the HUPO specimens. Some proteins, particularly cytokines, had highly variable concentrations between the different sample preparations, suggesting specific effects of certain anticoagulants on the stability or availability of these proteins. The linkage of antibody-based measurements from 66 different analytes with the combined MS/MS data from 18 different laboratories showed that protein detection and the quality of MS data increased with analyte concentration. The conclusions from these initial analyses are that the optimal blood preparation method is variable between analytes and that the discovery of blood proteins by MS can be extended to concentrations below the ng/mL range under certain circumstances. Continued developments in antibody-based methods will further advance the scientific goals of the PPP.« less

Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

PubMed

Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

2014-10-01

Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study.

PubMed

Auyeung, Vivian; Patel, Jignesh P; Abdou, John K; Vadher, Bipin; Bonner, Lynda; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen

2016-01-01

Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of ≥75 % and those <50 %. These groups of patients will have their illness perceptions, anticoagulation specific quality of life and beliefs about medications compared. Those patients in the time in therapeutic range <50 % group, will be then be invited to switch to a novel oral anticoagulant, as per local guidance. Those patients, who do switch, will then be followed longitudinally and have their adherence, illness perceptions, anticoagulation specific quality of life and beliefs about medications, re-evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term.

In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

NASA Astrophysics Data System (ADS)

Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

2011-05-01

Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

PubMed

Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

2017-05-01

Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery?

PubMed

Butwick, A J; Carvalho, B

2011-02-01

Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

Health care expenditures and therapeutic outcomes of a pharmacist-managed anticoagulation service versus usual medical care.

PubMed

Hall, Deanne; Buchanan, Julianne; Helms, Bethany; Eberts, Matthew; Mark, Scott; Manolis, Chronis; Peele, Pamela; Docimo, Anne

2011-07-01

To evaluate the differences in health care expenditures and therapeutic outcomes of patients receiving warfarin therapy management by a pharmacist-managed anticoagulation service compared with those receiving warfarin management by usual medical care. Retrospective, matched-cohort study. University of Pittsburgh Medical Center (UPMC) and UPMC Health Plan. Three hundred fifty adults who received warfarin therapy; 175 were managed by the pharmacist-managed anticoagulation service for at least 2 months between October 1, 2007, and September 30, 2008, (case patients) and 175 received usual care (matched comparison group). Medical claims data compared were direct anticoagulation cost and overall medical care costs, anticoagulation-related adverse events, hospitalizations and emergency department visits, frequency of international normalized ratio (INR) testing, and quantity of warfarin refills. Operational costs of the anticoagulation service were also calculated. The INR values and time within therapeutic range were assessed through anticoagulation service reports and laboratory results. The direct anticoagulation care cost was $35,465 versus $111,586 and the overall medical care cost was $754,191 versus $1,480,661 for the anticoagulation service group versus the usual care group. Accounting for operational and drug expenditure costs, the cost savings was $647,024 for the anticoagulation service group. The anticoagulation service group had significantly fewer anticoagulation-related adverse events (14 vs 41, p<0.0001), hospital admissions (3 vs 14, p<0.00001), and emergency department visits (58 vs 134, p<0.00001). The percentage of INR values in range and the percentage of time the INR values were in range were significantly higher in the anticoagulation service group (67.2% vs 54.6%, p<0.0001, and 73.7% vs 61.3%, p<0.0001, respectively). Compared with the usual care group, the anticoagulation service group had significantly more INR tests performed but demonstrated no significant difference in the quantity of drug refills. After accounting for operational costs, pharmacist-managed anticoagulation leads to reduced health care expenditure while improving therapeutic outcomes compared with usual medical care.

Adverse cardiovascular events in acute coronary syndrome with indications for anticoagulation

PubMed Central

Knight, Stacey; McCubrey, Raymond O.; Yuan, Zhong; Woller, Scott C.; Horne, Benjamin D.; Bunch, T. Jared; Le, Viet T.; Mills, Roger M.; Muhlestein, Joseph B.

2016-01-01

Objectives: Randomized acute coronary syndrome (ACS) trials testing various antithrombotic (AT) regimens have largely excluded patients with coexisting conditions and indications for anticoagulation (AC). The purpose of this study is to examine the 2-year clinical outcomes of patients with ACS with indication for AC due to venous thromboembolism (VTE) during hospitalization for the ACS event or a prior or new diagnosis of atrial fibrillation (AF) with a CHADS2 (Congestive heart failure; Hypertension; Age; Diabetes; previous ischemic Stroke) score ⩾2. Methods: ACS patients with AC indication from 2004 to 2009 were identified (n = 619). A Cox proportional hazards model was used to examine the primary efficacy outcome of major adverse cardiovascular events (MACE) including all-cause death, myocardial infarction (MI) or stroke. The primary explanatory variable was at-discharge antithrombotic strategy [single antiplatelet ± AC, dual antiplatelet (DAP) ± AC or AC only; referent DAP + AC]. Results: A total of 261 (42.2%) patients had a MACE event. AT strategy was not a significant factor for MACE (all p > 0.09). The factors associated with MACE were high mortality risk score [hazard ratio (HR)=1.87, 95% confidence interval (CI): 1.39– 2.52; p < 0.001), prior MI (HR = 1.44, 95% CI: 1.03–2.01; p= 0.033) and presentation of ST elevation MI (HR = 2.70, 95% CI: 1.61–4.51; p < 0.001) or non-ST elevation MI (HR = 1.70, 95% CI: 1.15–2.49; p < 0.001) compared with angina. Conclusions: In this real world observational study, the at-discharge AT strategy was not significantly associated with the 2-year risk of MACE. These findings do not negate the need for randomized trials to generate evidence-based approaches to management of this important population. PMID:26920371

Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

PubMed

Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

2014-07-01

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

Biobarcode assay for the oral anticoagulant acenocoumarol.

PubMed

Broto, Marta; Salvador, J Pablo; Galve, Roger; Marco, M Pilar

2018-02-01

A novel approach for therapeutic drug monitoring of oral anticoagulants (OA) in clinical samples is reported, based on a NP-based biobarcode assay. The proposed strategy uses specific antibodies for acenocumarol (ACL) covalently bound to magnetic particles (pAb236-MP) and a bioconjugate competitor (hACL-BSA) linked to encoded polystyrene probes (hACL-BSA-ePSP) on a classical competitive immunochemical format. By using this scheme ACL can be detected in low nM range (LOD, 0.96 ± 0.26, N = 3, in buffer) even in complex samples such as serum or plasma (LOD 4 ± 1). The assay shows a high reproducibility (%CV 1.1 day-to-day) and is robust, as it is demonstrated by the fact that ACL can be quantified in complex biological samples with a very good accuracy (slope = 0.97 and R 2 = 0.91, of the linear regression obtained when analyzing spiked vs measured values). Moreover, we have demonstrated that the biobarcode approach has the potential to overcome one of the main challenges of the multiplexed diagnostic, which is the possibility to measure in a single run biomarker targets present at different concentration ranges. Thus, it has been proven that the signal and the detectability can be modulated by just modifying the oligonucleotide load of the encoded probes. This fact opens the door for combining in the same assay encoded probes with the necessary oligonucleotide load to achieve the detectability required for each biomarker target. Copyright © 2017 Elsevier B.V. All rights reserved.

Trends in initiation of direct oral anticoagulant therapies for atrial fibrillation in a national population-based cross-sectional study in the French health insurance databases

PubMed Central

Huiart, Laetitia; Ferdynus, Cyril; Renoux, Christel; Beaugrand, Amélie; Lafarge, Sophie; Bruneau, Léa; Suissa, Samy; Maillard, Olivier; Ranouil, Xavier

2018-01-01

Objective Unlike several other national health agencies, French health authorities recommended that the newer direct oral anticoagulant (DOAC) agents only be prescribed as second choice for the treatment of newly diagnosed non-valvular atrial fibrillation (NVAF), with vitamin K antagonists (VKA) remaining the first choice. We investigated the patterns of use of DOACs versus VKA in the treatment of NVAF in France over the first 5 years of DOAC availability. We also identified the changes in patient characteristics of those who initiated DOAC treatment over this time period. Methods Based on the French National Health Administrative Database, we constituted a population-based cohort of all patients who were newly treated for NVAF between January 2011 and December 2015. Trends in drug use were described as the percentage of patients initiating each drug at the time of treatment initiation. A multivariate analysis using logistic regression model was performed to identify independent sociodemographic and clinical predictors of initial anticoagulant choice. Results The cohort comprised 814 446 patients who had received a new anticoagulant treatment for NVAF. The proportion of patients using DOACs as initial anticoagulant therapy reached 54% 3 months after the Health Ministry approved the reimbursement of dabigatran for NVAF, and 61% by the end of 2015, versus VKA use. In the multivariate analysis, we found that DOAC initiators were younger and healthier overall than VKA initiators, and this tendency was reinforced over the 2011–2014 period. DOACs were more frequently prescribed by cardiologists in 2012 and after (adjusted OR in 2012: 2.47; 95% CI 2.40 to 2.54). Conclusion Despite recommendations from health authorities, DOACs have been rapidly and massively adopted as initial therapy for NVAF in France. Observational studies should account for the fact that patients selected to initiate DOAC treatment are healthier overall, as failure to do so may bias the risk–benefit assessment of DOACs. PMID:29602837

Setting priorities in the health care sector - the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark.

PubMed

Poulsen, Peter Bo; Johnsen, Søren Paaske; Hansen, Morten Lock; Brandes, Axel; Husted, Steen; Harboe, Louise; Dybro, Lars

2017-01-01

Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets ("silo mentality"). The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF), the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a "drug cost only" perspective up to a "societal" perspective. All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the economic impact of this, all NOACs, except rivaroxaban, result in slightly lower health care costs compared with warfarin. The same picture was found applying the societal perspective. Many broad cost-effectiveness analyses of NOACs exist. However, in countries with budget focus in decision-making this information does not apply. The present study's case of oral anticoagulants has shown that decision-making should be based on health care or societal cost perspectives for optimal use of limited resources. Otherwise, the risk is that suboptimal decisions will be likely.

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

PubMed

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-09-01

Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.

PubMed

Henshaw, Daryl S; Turner, James D; Forest, Daniel J; Thompson, Garrett R; Weller, Robert S

Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available.

[Perioperative coagulation management in microsurgery: report of the consensus workshops in the course of the 31st and 32nd Annual Meeting of the German-language Working Group for microsurgery of the peripheral nerves and vessels (DAM) November 2009 in Erlangen and November 2010 in Basel].

PubMed

Schmitz, M; Riss, R; Kneser, U; Jokuszies, A; Harder, Y; Beier, J P; Schäfer, D J; Vogt, P M; Fansa, H; Andree, C; Pierer, G; Horch, R E

2011-12-01

Microsurgery is a very relevant component of reconstructive surgery. In this context anticoagulation plays an increasing role. At the moment there are no unanimously accepted prospective studies or generally accepted regimes available that could serve as evidence-based guidelines for the prevention of thrombosis in microsurgery. With regard to this problem the aim of a series of workshops during the annual meetings of the German-speaking group for microsurgery in 2009 and 2010 was to establish a first possible consensus. This article reflects the main aspects of the ongoing development of a generally acceptable guideline for anticoagulation in microsurgery as interim report of these consensus workshops. Basically there are 3 main agents in thromboprophylaxis available: antiplatelet drugs, dextran and heparin. In the course of the workshops no general use of aspirin or dextran for anticoagulation in microsurgery was recommended. The use of heparin as anticoagulation agent is advisable for different indications. Low molecular heparins (LMH) have certain advantages in comparison to unfractionated heparins (UFH) and are therefore preferred by most participants. Indications for UFH are still complex microsurgical revisions, renal failure and some specific constellations in patients undergoing reconstruction of the lower extremity, where the continuous administration of heparin is recommended. At the moment of clamp release a single-shot of UFH is still given by many microsurgeons, despite a lack of scientific evidence. Future prospective clinical trials and the establishment of a generally accepted evidence-based guideline regarding anticoagulation treatment in microsurgery are deemed necessary. © Georg Thieme Verlag KG Stuttgart · New York.

Appropriateness of Oral Anticoagulants for the Long-Term Treatment of Atrial Fibrillation in Older People: Results of an Evidence-Based Review and International Consensus Validation Process (OAC-FORTA 2016).

PubMed

Wehling, Martin; Collins, Ronan; Gil, Victor M; Hanon, Olivier; Hardt, Roland; Hoffmeister, Martin; Monteiro, Pedro; Quinn, Terence J; Ropers, Dieter; Sergi, Giuseppe; Verheugt, Freek W A

2017-07-01

Age appropriateness of anticoagulants for stroke prevention in atrial fibrillation is uncertain. To review oral anticoagulants for the treatment of atrial fibrillation in older (age >65 years) people and to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability using the Fit-fOR-The-Aged (FORTA) classification. We performed a structured comprehensive review of controlled clinical trials and summaries of individual product characteristics to assess study and total patient numbers, quality of major outcome data and data of geriatric relevance. The resulting evidence was discussed in a round table with an interdisciplinary panel of ten European experts. Decisions on age appropriateness were made using a Delphi process. For the eight drugs included, 380 citations were identified. The primary outcome results were reported in 32 clinical trials with explicit and relevant data on older people. Though over 24,000 patients aged >75/80 years were studied for warfarin, data on geriatric syndromes were rare (two studies reporting on frailty/falls/mental status) and missing for all other compounds. Apixaban was rated FORTA-A (highly beneficial). Other non-vitamin K antagonist oral anticoagulants (including low/high-intensity dabigatran and high-intensity edoxaban) and warfarin were assigned to FORTA-B (beneficial). Phenprocoumon, acenocoumarol and fluindione were rated FORTA-C (questionable), mainly reflecting the absence of data. All non-vitamin K antagonist oral anticoagulants and warfarin were classified as beneficial or very beneficial in older persons (FORTA-A or -B), underlining the overall positive assessment of the risk/benefit ratio for these drugs. For other vitamin-K antagonists regionally used in Europe, the lack of evidence should challenge current practice.

A PK-PD model-based assessment of sugammadex effects on coagulation parameters.

PubMed

Bosch, Rolien; van Lierop, Marie-José; de Kam, Pieter-Jan; Kruithof, Annelieke C; Burggraaf, Jacobus; de Greef, Rik; Visser, Sandra A G; Johnson-Levonas, Amy O; Kleijn, Huub-Jan

2016-03-10

Exposure-response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30min after administration of 16mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Chitosan-based ultrathin films as antifouling, anticoagulant and antibacterial protective coatings.

PubMed

Bulwan, Maria; Wójcik, Kinga; Zapotoczny, Szczepan; Nowakowska, Maria

2012-01-01

Ultrathin antifouling and antibacterial protective nanocoatings were prepared from ionic derivatives of chitosan using layer-by-layer deposition methodology. The surfaces of silicon, and glass protected by these nanocoatings were resistant to non-specific adsorption of proteins disregarding their net charges at physiological conditions (positively charged TGF-β1 growth factor and negatively charged bovine serum albumin) as well as human plasma components. The coatings also preserved surfaces from the formation of bacterial (Staphylococcus aureus) biofilm as shown using microscopic studies (SEM, AFM) and the MTT viability test. Moreover, the chitosan-based films adsorbed onto glass surface demonstrated the anticoagulant activity towards the human blood. The antifouling and antibacterial actions of the coatings were correlated with their physicochemical properties. The studied biologically relevant properties were also found to be dependent on the thickness of those nanocoatings. These materials are promising for biomedical applications, e.g., as protective coatings for medical devices, anticoagulant coatings and protective layers in membranes.

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

PubMed

Shum, H P; Yan, W W; Chan, T M

2015-04-01

Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs.

PubMed

Abraham, Neena S; El-Serag, Hashem B; Johnson, Michael L; Hartman, Christine; Richardson, Peter; Ray, Wayne A; Smalley, Walter

2005-10-01

Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. This was a cross-sectional study among veterans prescribed a nonsteroidal anti-inflammatory drug (NSAID) from January 1, 2002, to December 31, 2002. Prescription data were linked to inpatient and outpatient medical records and death files. The population was characterized as high risk based on the following: age 65 years or older, concurrent corticosteroid or anticoagulant use, history of peptic ulcer, and high average daily dose of NSAIDs. Adherence was defined as the prescription of a traditional NSAID with gastroprotection or a coxib in high-risk NSAID users. Univariate and multivariate analyses assessed the potential predictors of adherence. Three hundred three thousand seven hundred eighty-seven met our definition of high risk. Most (97.3%) were male; 55.6% were white, 9.6% black, and 34.8% of other/unknown race. Age 65 years or older was the largest high-risk subset (87.1%). Overall, only 27.2% of high-risk veterans (n = 82,766) were prescribed an adherent strategy. Among veterans with at least 2 risk factors, adherence was 39.7%; among those with 3 risk factors, adherence was 41.8%. Predictors of adherence included history of upper gastrointestinal events, anticoagulant use, rheumatologic disease, high Deyo comorbidity index score, use of low-dose salicylates, and concurrent corticosteroid use. Predictors of nonadherence included prescriptions > or =90 days and high average daily dose of NSAIDs. Adherence to evidence-based guidelines for safe prescription of NSAIDs in the Department of Veterans Affairs is low (27.2%). The likelihood of adherence is further decreased if veterans are prescribed NSAIDs for > or=90 days.

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

PubMed

Fuchs, P; Vogel, T; Lang, P-O

2015-08-01

To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; P<0.05), diabetes (C: 90.0%, G: 60.0%, MG: 55.0%; P<0.05), hypertension (C: 85.0%, G: 55.0%, MG: 60.0%; P<0.05) and female gender (C: 80.0%, G: 35.0%, MG: 25.0%; P<0.05). The quality of renal function was however a more secondary criteria (C: 15.0%, G: 5.0%, MG: 0.0%; P<0.05). General practitioners considered most frequently the presence of underlying heart disease (C: 35.0%, G: 5.0%, MG: 45.0%; P<0.05) as well as usual cardiovascular risk factors (overweight, dyslipidaemia; P<0.05). Risk of bleeding, however, was observed by 76.7% of physicians in the clinical situation presented (C: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Thromboembolic complications of thyroid storm.

PubMed

Min, T; Benjamin, S; Cozma, L

2014-01-01

Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Early recognition and prompt treatment are essential. Atrial fibrillation can occur in up to 40% of patients with thyroid storm. Studies have shown that hyperthyroidism increases the risk of thromboembolic events. There is no consensus with regard to the initiation of anticoagulation for atrial fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated if the risk is low on a CHADS2 score; however, this should be considered in patients with thyroid storm or severe thyrotoxicosis with impending storm irrespective of the CHADS2 risk, as it appears to increase the risk of thromboembolic episodes. Herein, we describe a case of thyroid storm complicated by massive pulmonary embolism. Diagnosis of thyroid storm is based on clinical findings. Early recognition and prompt treatment could lead to a favourable outcome.Hypercoagulable state is a recognised complication of thyrotoxicosis.Atrial fibrillation is strongly associated with hyperthyroidism and thyroid storm.Anticoagulation should be considered for patients with severe thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.Patients with severe thyrotoxicosis and clinical evidence of thrombosis should be immediately anticoagulated until hyperthyroidism is under control.

Assessing the risk of recurrent venous thromboembolism--a practical approach.

PubMed

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice.

Vena cava filter retrieval in therapeutically anticoagulated patients.

PubMed

Schmelzer, Thomas M; Christmas, A Britton; Taylor, Dennis A; Heniford, B Todd; Sing, Ronald F

2008-12-01

Vena cava filters (VCFs) are indicated in patients with active venous thromboembolism and are a contraindication to therapeutic anticoagulation. When patients can be anticoagulated, VCFs can be removed; however, patients often have anticoagulation discontinued during the retrieval procedure, leaving them at risk for pulmonary embolism (PE). The authors evaluated their experience with retrieving VCFs in therapeutically anticoagulated patients. Data from a prospectively collected database of patients with VCFs placed between January 2005 and September 2007 were reviewed. The retrievals in therapeutically anticoagulated patients (international normalized ratio, 2.0-3.4) were performed using a strict protocol, including preretrieval and postretrieval cavograms. All retrievals were performed in the operating room, and patients were discharged home the same day and examined within 7 to 14 days. Descriptive statistics including means and counts were calculated. One hundred thirteen VCF removals occurred during the study period; 62 were attempted on anticoagulated patients (42 male and 20 female patients; mean age, 36.5 years). Thirty-five patients (56%) had VCFs placed for prophylaxis, 22 (35%) had deep venous thromboses or PEs but had contraindications to anticoagulation, and 5 (8%) were on anticoagulation, which was discontinued perioperatively for major surgical operations. The mean time the filters were in place was 153.7 days (range, 22-684 days). No extravasation was seen on postretrieval cavography. Eight of 62 removal attempts in anticoagulated patients were unsuccessful. One patient had a postoperative pneumothorax that was successfully managed without intervention. There were no operative bleeding complications, and no hematomas or contusions were seen at follow-up. The retrieval of VCFs in therapeutically anticoagulated patients can be performed without complication. Given the perioperative risk for PE, anticoagulation should not be discontinued for VCF retrieval.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

PubMed

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

Quality of oral anticoagulation with phenprocoumon in regular medical care and its potential for improvement in a telemedicine-based coagulation service--results from the prospective, multi-center, observational cohort study thrombEVAL.

PubMed

Prochaska, Jürgen H; Göbel, Sebastian; Keller, Karsten; Coldewey, Meike; Ullmann, Alexander; Lamparter, Heidrun; Jünger, Claus; Al-Bayati, Zaid; Baer, Christina; Walter, Ulrich; Bickel, Christoph; ten Cate, Hugo; Münzel, Thomas; Wild, Philipp S

2015-01-23

The majority of studies on quality of oral anticoagulation (OAC) therapy with vitamin K-antagonists are performed with short-acting warfarin. Data on long-acting phenprocoumon, which is frequently used in Europe for OAC therapy and is considered to enable more stable therapy adjustment, are scarce. In this study, we aimed to assess quality of OAC therapy with phenprocoumon in regular medical care and to evaluate its potential for optimization in a telemedicine-based coagulation service. In the prospective observational cohort study program thrombEVAL we investigated 2,011 patients from regular medical care in a multi-center cohort study and 760 patients from a telemedicine-based coagulation service in a single-center cohort study. Data were obtained from self-reported data, computer-assisted personal interviews, and laboratory measurements according to standard operating procedures with detailed quality control. Time in therapeutic range (TTR) was calculated by linear interpolation method to assess quality of OAC therapy. Study monitoring was carried out by an independent institution. Overall, 15,377 treatment years and 48,955 international normalized ratio (INR) measurements were analyzed. Quality of anticoagulation, as measured by median TTR, was 66.3% (interquartile range (IQR) 47.8/81.9) in regular medical care and 75.5% (IQR 64.2/84.4) in the coagulation service (P <0.001). Stable anticoagulation control within therapeutic range was achieved in 63.8% of patients in regular medical care with TTR at 72.1% (IQR 58.3/84.7) as compared to 96.4% of patients in the coagulation service with TTR at 76.2% [(IQR 65.6/84.7); P = 0.001)]. Prospective follow-up of coagulation service patients with pretreatment in regular medical care showed an improvement of the TTR from 66.2% (IQR 49.0/83.6) to 74.5% (IQR 62.9/84.2; P <0.0001) in the coagulation service. Treatment in the coagulation service contributed to an optimization of the profile of time outside therapeutic range, a 2.2-fold increase of stabile INR adjustment and a significant decrease in TTR variability by 36% (P <0.001). Quality of anticoagulation with phenprocoumon was comparably high in this real-world sample of regular medical care. Treatment in a telemedicine-based coagulation service substantially improved quality of OAC therapy with regard to TTR level, frequency of stable anticoagulation control, and TTR variability. ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.

Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: a retrospective cross-sectional study.

PubMed

Fenta, Teferi Gedif; Assefa, Tamrat; Alemayehu, Bekele

2017-06-06

Warfarin is the most widely used anticoagulant in the world. The difficulty of managing warfarin contributes to great potential for patient harm, both from excessive anticoagulation and insufficient anticoagulation. This study assessed the International Normalized Ratio (INR) control outcome measures and warfarin dose adjustment practices at cardiology and hematology outpatient clinics at a teaching hospital in Addis Ababa, Ethiopia. The study was based on a cross - sectional study design involving 360 retrospective patients' chart review among outpatients who received warfarin for its various indications. The mean frequency of INR monitoring per patient was 62.9 days (17.2-143.7 days). Patients spent 52.2%, 29.0% and 18.8% of the time in sub-therapeutic, therapeutic and supra-therapeutic ranges, respectively. The daily warfarin dose was increased 50.9% and 36.9% and decreased in 52.8% and 60.9% of the time for occurrences of sub-therapeutic and supra-therapeutic INRs to achieve target ranges of 2.0-3.0 and 2.5-3.5, respectively. The quality of anticoagulation management with warfarin among outpatients in Tikur Anbessa Specialized Hospital was sub-optimal. This was reflected by low Time in Therapeutic Range (TTR), longer than recommended INR monitoring frequency, and minimal actions taken to adjust warfarin dose after occurrences of non-therapeutic INRs.

Determinants of antithrombotic choice for patent foramen ovale in cryptogenic stroke.

PubMed

Thaler, David E; Ruthazer, Robin; Weimar, Christian; Serena, Joaquín; Mattle, Heinrich P; Nedeltchev, Krassen; Mono, Marie-Luise; Di Angelantonio, Emanuele; Elkind, Mitchell S V; Di Tullio, Marco R; Homma, Shunichi; Michel, Patrik; Meier, Bernhard; Furlan, Anthony J; Lutz, Jennifer S; Kent, David M

2014-11-18

We examined the influence of clinical, radiologic, and echocardiographic characteristics on antithrombotic choice in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO), hypothesizing that features suggestive of paradoxical embolism might lead to greater use of anticoagulation. The Risk of Paradoxical Embolism Study combined 12 databases to create the largest dataset of patients with CS and known PFO status. We used generalized linear mixed models with a random effect of component study to explore whether anticoagulation was preferentially selected based on the following: (1) younger age and absence of vascular risk factors, (2) "high-risk" echocardiographic features, and (3) neuroradiologic findings. A total of 1,132 patients with CS and PFO treated with anticoagulation or antiplatelets were included. Overall, 438 participants (39%) were treated with anticoagulation with a range (by database) of 22% to 54%. Treatment choice was not influenced by age or vascular risk factors. However, neuroradiologic findings (superficial or multiple infarcts) and high-risk echocardiographic features (large shunts, shunt at rest, and septal hypermobility) were predictors of anticoagulation use. Both antithrombotic regimens are widely used for secondary stroke prevention in patients with CS and PFO. Radiologic and echocardiographic features were strongly associated with treatment choice, whereas conventional vascular risk factors were not. Prior observational studies are likely to be biased by confounding by indication. © 2014 American Academy of Neurology.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

PubMed

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial models of mammalian metabolism: production of novel alpha-diketone metabolites of warfarin and phenprocoumon using Aspergillus niger.

PubMed

Rizzo, J D; Davis, P J

1988-12-01

1. The coumarin anticoagulants warfarin and phenprocoumon were metabolized by Aspergillus niger via oxidative ring cleavage to yield the corresponding alpha-diketone metabolites. 2. Structural identification was based upon physical, spectral, and chromatographic comparisons of isolated metabolites and synthetic standards generated by the oxidative cleavage of warfarin or phenprocoumon with pyridinium chlorochromate. 3. This pathway of metabolism has been previously observed for coumarin anticoagulants in mammalian systems.

Backbone modified TBA analogues endowed with antiproliferative activity.

PubMed

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Varra, Michela; Vellecco, Valentina; Bucci, Mariarosaria; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2017-05-01

The thrombin binding aptamer (TBA) is endowed with antiproliferative properties but its potential development is counteracted by the concomitant anticoagulant activity. Five oligonucleotides (ODNs) based on TBA sequence (GGTTGGTGTGGTTGG) and containing l-residues or both l-residues and inversion of polarity sites have been investigated by NMR and CD techniques for their ability to form G-quadruplex structures. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay), and their resistance in fetal bovine serum have been tested. CD and NMR data suggest that the investigated ODNs are able to form right- and left-handed G-quadruplex structures. All ODNs do not retain the anticoagulant activity characteristic of TBA but are endowed with a significant antiproliferative activity against two cancerous cell lines. Their resistance in biological environment after six days is variable, depending on the ODN. A comparison between results and literature data suggests that the antiproliferative activity of the TBA analogues investigated could depends on two factors: a) biological pathways and targets different from those already identified or proposed for other antiproliferative G-quadruplex aptamers, and b) the contribution of the guanine-based degradation products. Modified TBA analogues containing l-residues and inversion of polarity sites lose the anticoagulant activity but gain antiproliferative properties against two cancer cell lines. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

PubMed Central

Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

2015-01-01

Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24). Conclusions Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia‐risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe. PMID:25581108

Optimal duration of anticoagulation in patients with venous thromboembolism.

PubMed

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

Therapeutic management of acute pulmonary embolism.

PubMed

Tromeur, Cécile; Van Der Pol, Liselotte M; Couturaud, Francis; Klok, Frederikus A; Huisman, Menno V

2017-08-01

Acute pulmonary embolism (PE) is a potentially fatal manifestation of venous thromboembolism. Prompt anticoagulant treatment is crucial for PE patients, which can decrease morbidity and mortality. Risk assessment is the cornerstone of the therapeutic management of PE. It guides physicians to the most appropriate treatment and selects patients for early discharge or home treatment. Areas covered: Here, we review the current treatments of acute PE according to contemporary risk stratification strategies, highlighting each step of PE therapeutic management. Expert commentary: Currently, direct oral anticoagulants (DOACs) represent the first-line therapy of patients presenting with non-high risk PE with a better risk-benefit ratios than vitamin K antagonists (VKAs) due to lower risk of major bleeding. Only high-risk patients with PE who present in shock should be treated with systematic thrombolysis, while surgical thrombectomy or catheter direct thrombolysis (CDT) should only be considered when thrombolysis is contraindicated because of too high bleeding risk.

Current limitations of the assessment of haemostasis in adult extracorporeal membrane oxygenation patients and the role of point-of-care testing.

PubMed

Venkatesh, K; Nair, P S; Hoechter, D J; Buscher, H

2016-11-01

Haemostatic perturbations are commonly seen in extracorporeal membrane oxygenation (ECMO) patients and remain a clinical challenge, contributing significantly to morbidity and mortality. The approach to anticoagulation monitoring and the management of bleeding varies considerably across ECMO centres. Routine laboratory tests have their limitations in terms of turnaround time and specificity of information provided. Newer point-of-care testing (POCT) for coagulation may overcome these issues, as it provides information about the entire coagulation pathway from clot initiation to lysis. It is also possible to obtain qualitative information on platelet function from these tests. Furthermore, the ability to incorporate these results into a goal-directed algorithm to manage bleeding with targeted transfusion strategies appears particularly attractive and cost effective. Further studies are required to evaluate the utility of POCT to optimise bleeding and anticoagulation management in these complex patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biello, D.R.

The optimal strategy for diagnostic evaluation of patients with suspected pulmonary thromboembolism (PE) is subject of controversial and often conflicting opinions. If untreated, as many as 30% of patients with PE may die. Conversely, anticoagulant therapy significantly decreases mortality from PE, but bleeding complications occur. Underdiagnosis may result in a preventable death, and overdiagnosis may lead to significant hemorrhage from unnecessary anticoagulant therapy. This article outlines a practical guide for the use of pulmonary ventilation-perfusion (V-P) scintigraphy in patients with suspected PE. Perfusion imaging involves the intravenous injection of radiolabeled particles ranging from 10 to 60 ..mu..m in diameter (technetiummore » Tc 99m macroaggregated albumin or technetium Tc 99m serum albumin microspheres); these particles are trapped in the capillaries and precapillary arterioles of the lung. The radiolabeled particles are distributed to the lungs in proportion to regional pulmonary blood flow. The correspondence of perfusion defects to bronchopulmonary segments is best appreciated in the posterior oblique views.« less

A Phase 2, randomized, partially blinded, active-controlled study assessing the efficacy and safety of variable anticoagulation reversal using the REG1 system in patients with acute coronary syndromes: results of the RADAR trial

PubMed Central

Povsic, Thomas J.; Vavalle, John P.; Aberle, Laura H.; Kasprzak, Jaroslaw D.; Cohen, Mauricio G.; Mehran, Roxana; Bode, Christoph; Buller, Christopher E.; Montalescot, Gilles; Cornel, Jan H.; Rynkiewicz, Andrzej; Ring, Michael E.; Zeymer, Uwe; Natarajan, Madhu; Delarche, Nicolas; Zelenkofske, Steven L.; Becker, Richard C.; Alexander, John H.

2013-01-01

Aims We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. Methods and results Non-ST-elevation ACS patients (n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. Conclusion At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation. Clinical Trials Registration: ClinicalTrials.gov NCT00932100. PMID:22859796

[Low molecular weight heparin and non valvular atrial fibrillation].

PubMed

Ederhy, S; Di Angelantonio, E; Meuleman, C; Janower, S; Boccara, F; Cohen, A

2006-12-01

Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

A promising oral fucoidan-based antithrombotic nanosystem: development, activity and safety

NASA Astrophysics Data System (ADS)

da Silva, L. C. R. P.; Todaro, V.; do Carmo, F. A.; Frattani, F. S.; de Sousa, V. P.; Rodrigues, C. R.; Sathler, P. C.; Cabral, L. M.

2018-04-01

Fucoidan-loaded nanoparticles emerge as great candidates for oral anticoagulant therapy, due to increases in the bioavailability and circulation time of this natural anticoagulant. Crosslinks between chitosan chains are performed using glutaraldehyde to confer higher gastric pH resistance to nanoparticle matrices. In this work, chitosan-fucoidan nanoparticles, without (NpCF) and with glutaraldehyde crosslink (NpCF 1% and NpCF 2%), were prepared to evaluate their anticoagulant, antithrombotic and hemorrhagic profiles. Nanoparticles were characterized by average diameter (AD), polydispersity index, zeta potential, Fourier transform infrared spectroscopy and fucoidan in vitro release. Anticoagulant and antithrombotic activities were determined by in vitro and in vivo models, respectively. Hemorrhagic profile was in vivo evaluated by tail bleeding assay. Preparations showed nanometric and homogeneous ADs. Zeta potentials of NpCF and NpCF 1% were stable over the gastrointestinal pH range, which was confirmed by low fucoidan release in gastric and enteric media. In pH 7.4, NpCF and NpCF 1% demonstrated fucoidan release of 65.5% and 60.6%, respectively, within the first 24 h. In comparison to fucoidan, NpCF and NpCF 1% showed increased in vitro anticoagulant activity. A significant difference in the oral antithrombotic profile of NpCF 1% was found in comparison to fucoidan. Bleeding profile of NpCF and NpCF 1% showed no differences to the control group, indicating the safety of these systems. Surprisingly, the oral antithrombotic profile of commercially available fucoidan, from Fucus vesiculosus, has not been previously determined, which reveals new possibilities. In this work, significant advances were observed in the anticoagulant and antithrombotic profiles of fucoidan through the preparation of NpCF 1%.

Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

2014-10-01

The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Predicting Hemorrhagic Transformation of Acute Ischemic Stroke: Prospective Validation of the HeRS Score.

PubMed

Marsh, Elisabeth B; Llinas, Rafael H; Schneider, Andrea L C; Hillis, Argye E; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F

2016-01-01

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

PubMed Central

Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus

2012-01-01

Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538

Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

PubMed

Terrell, M R; Walenga, J M; Koza, M J; Pifarré, R

1996-08-01

Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

Variability in Antithrombotic Therapy Regimens Peri-TAVR: A Single Academic Center Experience.

PubMed

Rossi, Jeffrey E; Noll, Andrew; Bergmark, Brian; McCabe, James M; Nemer, David; Okada, David R; Vasudevan, Anant; Davidson, Michael; Welt, Frederick; Eisenhauer, Andrew; Shah, Pinak; Giugliano, Robert

2015-12-01

The aim of this study was to describe peri-procedural antithrombotic use in patients undergoing transcatheter aortic valve replacement (TAVR) at a single academic medical center. Retrospective collection of antiplatelet and anticoagulant use during the index hospitalization for all patients undergoing TAVR at our institution from April 2009 through March 2014. Of a total of 255 patients undergoing the procedure, 132 (51%) had an indication for anticoagulation pre-TAVR and 92 (70% of those with an indication) were on treatment. On discharge, 106 patients (44% of total surviving to discharge, 73% of those surviving with an indication for anticoagulation) were treated with oral anticoagulation. Of these patients, 89 (84%) were discharged on aspirin and an oral anticoagulant without clopidogrel. Only 122 (51% of total patients) were discharged on the regimen of aspirin and clopidogrel alone. Peri-procedural antithrombotic regimens vary greatly following TAVR. More than half of patients have an indication for anticoagulation following the procedure. Most patients at our institution who require anticoagulation are discharged on aspirin and an oral anticoagulant, though the optimal regimen requires further investigation.

The future of anticoagulation clinics.

PubMed

Macik, B Gail

2003-01-01

Anticoagulation therapy is the foundation of treatment for thromboembolic disorders; and coumarin derivatives (warfarin in the United States) are the only orally administered anticoagulant medications currently available. Due to the expense and relative difficulties associated with this route of administration, parenteral drugs are not used routinely for long-term therapy, leaving warfarin as the anticoagulant of choice in the outpatient setting. The management of warfarin is problematic, however, due the nuances of its pharmacodynamic and pharmacokinetic profile and the requirement for frequent monitoring of blood levels. Although management by anticoagulation clinics is considered the gold standard for warfarin therapy, management by an anticoagulation clinic may not be the optimal option from a clinician's view and, in many cases, may not be an option at all. Anticoagulation clinics may impinge on the doctor-patient relationship. Difficulties of communication and reimbursement are not ameliorated by a specialty clinic. Innovations in warfarin management, including patient self-management and computerized dosing programs, are alternatives for improved care that are available with or without input by an anticoagulation service. New oral drugs on the horizon do not require the same intensity of monitoring and do not present the same pharmacodynamic problems associated with warfarin. Warfarin will become obsolete in the foreseeable future. If anticoagulation clinics continue, they must re-define their role as the major part of the workload, warfarin management, disappears. To adapt, clinics must strengthen and enhance their role as coordinators and educators, and less so, managers of anticoagulation therapy.

Optimal duration of anticoagulation in patients with venous thromboembolism

PubMed Central

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Valle, Fabio Dalla; Pesavento, Raffaele

2011-01-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. PMID:21808129

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art.

PubMed

Iapichino, Giacomo E; Bianchi, Paolo; Ranucci, Marco; Baryshnikova, Ekaterina

2017-06-01

Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Assessing the risk of recurrent venous thromboembolism – a practical approach

PubMed Central

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice. PMID:26316770

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS₂ [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS₂ and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed Central

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Objectives Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. Methods A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS2 and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Results Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Conclusion Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse. PMID:25053883

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing

PubMed Central

Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2017-01-01

Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing. PMID:28771571

Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

PubMed Central

Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

2016-01-01

Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

PubMed

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

PubMed

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry

PubMed Central

Papp, Judit; Zima, Endre; Bover, Ramon; Karaliute, Rasa; Rossi, Andrea; Szymanski, Catherine; Troccoli, Rossella; Schneider, Jonas; Fagerland, Morten Wang; Camm, A John; Atar, Dan

2017-01-01

Abstract Aims In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. Methods From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. Results A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). Conclusion According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that NOAC use is increasing and there is a significant decrease in VKA use. PMID:28329309

Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry.

PubMed

Papp, Judit; Zima, Endre; Bover, Ramon; Karaliute, Rasa; Rossi, Andrea; Szymanski, Catherine; Troccoli, Rossella; Schneider, Jonas; Fagerland, Morten Wang; Camm, A John; Atar, Dan

2017-07-01

In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that NOAC use is increasing and there is a significant decrease in VKA use. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

PubMed

Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Albumin Loss and Citrate Load in Pre-Dilution High Cut-Off-CVVHDF with Regional Citrate (18 mmol/L) and High Cut-Off CVVHD with Systemic Heparin: An in vitro Study.

PubMed

Villa, Gianluca; Neri, Mauro; De Rosa, Silvia; Samoni, Sara; Chelazzi, Cosimo; Romagnoli, Stefano; Lorenzin, Anna; de Cal, Massimo; Ronco, Claudio; De Gaudio, Angelo Raffaele

2018-06-08

Convective therapies with high cut-off membranes (HCO) are usually not recommended because of theoretical excessive albumin loss. The aim of this in vitro study is to demonstrate the noninferior safety of pre-dilution hemodiafiltration with HCO (HCO-CVVHDF) with isotonic citrate anticoagulation (18 mmol/L) with respect to heparin anticoagulated hemodialysis with HCO (HCO-CVVHD) in terms of albumin removal and citrate load. -Albumin removal was compared in vitro between 3 pre--dilution-HCO-CVVHDF with citrate anticoagulation and 3 -HCO-CVVHD with heparin anticoagulation during 30-min single-pass and 180-min recirculation phases. Considering concentrations and flows in the extracorporeal circuit, the transmembrane albumin removal was 2.06 (1.51; 2.09) g and 2.09 (1.9; 2.8) g respectively for HCO-CVVHDF and HCO-CVVHD, during the single-pass phase; 2.8 (2.67; 4.59) g and 2.54 (2.35; 4.67) g, respectively, for HCO-CVVHDF and HCO-CVVHD during the recirculation phase. Based on the citrate saturation coefficients, a citrate metabolic load of 8.86 mmol/h has been calculated for HCO-CVVHDF. HCO-CVVHDF performed with regional anticoagulation with 18 mmol/L citrate solution does not induce higher -albumin transmembrane removal compared to HCO-CVVHD. © 2018 S. Karger AG, Basel.

Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

PubMed

Yates, Sean; Sarode, Ravi

2013-11-01

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

New oral anticoagulants--a review.

PubMed

Ghanima, Waleed; Atar, Dan; Sandset, Per Morten

2013-10-01

Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors' clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.

Atrial fibrillation and stroke: the evolving role of rhythm control.

PubMed

Patel, Taral K; Passman, Rod S

2013-06-01

Atrial fibrillation (AF) remains a major risk factor for stroke. Unfortunately, clinical trials have failed to demonstrate that a strategy of rhythm control--therapy to maintain normal sinus rhythm (NSR)--reduces stroke risk. The apparent lack of benefit of rhythm control likely reflects the difficulty in maintaining NSR using currently available therapies. However, there are signals from several trials that the presence of NSR is indeed beneficial and associated with better outcomes related to stroke and mortality. Most electrophysiologists feel that as rhythm control strategies continue to improve, the crucial link between rhythm control and stroke reduction will finally be demonstrated. Therefore, AF specialists tend to be aggressive in their attempts to maintain NSR, especially in patients who have symptomatic AF. A step-wise approach from antiarrhythmic drugs to catheter ablation to cardiac surgery is generally used. In select patients, catheter ablation or cardiac surgery may supersede antiarrhythmic drugs. The choice depends on the type of AF, concurrent heart disease, drug toxicity profiles, procedural risks, and patient preferences. Regardless of strategy, given the limited effectiveness of currently available rhythm control therapies, oral anticoagulation is still recommended for stroke prophylaxis in AF patients with other stroke risk factors. Major challenges in atrial fibrillation management include selecting patients most likely to benefit from rhythm control, choosing specific antiarrhythmic drugs or procedures to achieve rhythm control, long-term monitoring to gauge the efficacy of rhythm control, and determining which (if any) patients may safely discontinue anticoagulation if long-term NSR is achieved.

Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

PubMed Central

Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

2016-01-01

New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

The role of oral anticoagulants in epistaxis.

PubMed

Buchberger, A M S; Baumann, A; Johnson, F; Peters, N; Piontek, G; Storck, K; Pickhard, A

2018-06-23

The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants. The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication. 600 adult cases, with a median age of 66.6 years were identified with active bleeding. 66.8% of all cases were anticoagulated. Classic oral anticoagulants (COAC) were three times more common in patients than new-generation oral anticoagulants (NOAC). Recurrent bleeding was significantly associated with oral anticoagulants (OAC) (p = 0.014) and bleeding location was most often anterior (p = 0.006). In contrast, severe cases, which required surgery or embolization were significantly more likely in non-anticoagulated middle-aged patients with posterior bleedings (p < 0.05). In our epistaxis cohort, OAC were highly overrepresented (40%) when compared to the general German population (1%) but COAC as well as NOAC played only a minor role in severe courses of epistaxis. Oral anticoagulation, especially with new-generation drugs, is not associated with more complicated and severe courses of epistaxis, but rather with recurrent bleeding. One should keep this information in mind when triaging the patient in the emergency room and when planning further procedures.

New horizons in anticoagulation: Direct oral anticoagulants and their implications in oral surgery

PubMed Central

Ripollés-de Ramón, Jorge; Collado-Yurrita, Luis; Vaello-Checa, Iris; Colmenero-Ruiz, Constantino; Helm, Alexandra; Ciudad-Cabañas, Maria-José; Serrano-Cuenca, Victoriano

2017-01-01

Background Thrombotic disorders remain a leading cause of death in the Western World. For decades, vitamin K antagonists used in the prevention of this pathology, such as warfarin or sintrom, were the only oral agents available for long-term anticoagulation, in spite of their disadvantages. Material and Methods An electronic database search was carried out on MedLine and The Cochrane Library Plus, without restrictions on the type of study nor dates, in English and Spanish. Abstracts were reviewed, and complete articles if necessary, considering all articles that included recommendations on DOACs and oral surgery. Results In recent years, the so-called “new oral anticoagulants” have been introduced in clinical practice to treat those patients whose medical conditions require long-term anticoagulant treatment, replacing traditional oral anticoagulants. Conclusions The new oral anticoagulants represent new therapeutic options, with a number of advantages such as poor interaction with food, minor drug interactions, and do not require periodic dose adjustments or routine controls. The purpose of this review is to establish an update on the new oral anticoagulants: Dabigatran, Rivarozaban, Apixaban and Edoxaban. Key words:Novel oral anticoagulants, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, bleeding management, oral surgery, Anti-IIa, Anti Xa. PMID:28809374

[Clinical spectrum of patients with spontaneous retroperitoneal hematomas].

PubMed

Sánchez-González, Amada; Riancho-Zarrabeitia, Leyre; Salmón-González, Zaida; Riancho, José Antonio; Valero, Carmen

2015-10-05

Spontaneous retroperitoneal hematoma (SRH) is a potentially fatal clinical entity requiring immediate recognition and intervention. The clinical records of 18-year-old and older patients admitted to the University Hospital Marqués de Valdecilla from 2003 to 2013 were reviewed. "Spontaneous" was defined as unrelated to trauma, invasive procedures or bleeding due to aortic aneurysm rupture. Thirty-four patients with SRH (44% were on anticoagulant drugs). One-third of cases had chronic renal insufficiency. Abdominal pain was the most common symptom both in anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in non-anticoagulated patients). About one half of the patients developed shock. A CT scan was the most commonly performed diagnostic test, followed by abdominal ultrasound. Most cases were managed conservatively (80%). More than half of the patients (66%) restarted anticoagulation therapy after the acute event with a mean delay of 19 days (range 2-90 days). None of them suffered a new bleeding episode. Restarting the anticoagulation treatment after hematoma resolution seems to be a safe practice. There is an increasing frequency of SRH in non-anticoagulated patients. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Evaluation of the anticoagulant potential of polysaccharide-rich fractions extracted from macroalgae.

PubMed

Adrien, Amandine; Dufour, Delphine; Baudouin, Stanislas; Maugard, Thierry; Bridiau, Nicolas

2017-09-01

The aim of this study was to evaluate the potential anticoagulant activity of sulphated polysaccharide-containing extracts of six french edible marine macroalgae. Aqueous extracts of brown (Himanthalia elongata, Laminaria digitata, Ascophyllum nodosum, Fucus vesiculosus), green (Ulva lactuca) and red (Chondrus crispus) macroalgae were prepared and their biochemical properties were determined, including major biomolecules, sulphate and ash contents. The anticoagulant activity of each extract was investigated using different scales from the specific antithrombin-dependent pathway (anti-Xa and anti-IIa) to the intrinsic and/or common (Activated Partial Thromboplastin Time, APTT), extrinsic (Prothrombin Time, PT) or common (Thrombin Time, TT) anticoagulant pathways, and compared with those of commercial anticoagulants, heparin and Lovenox®. Laminaria digitata, Fucus vesiculosus and Chondrus crispus extracts showed a significant APTT anticoagulant capacity, only 5-fold lower than that of Lovenox®, which is a pure low molecular weight heparin used as an anticoagulant agent to prevent pulmonary embolism in patients undergoing surgery.

[Cataract surgery under topical anesthesia with oral anticoagulants].

PubMed

Wirbelauer, C; Weller, A; Häberle, H; Pham, D T

2004-09-01

Approximately 14 % of cataract surgery patients receive blood-thinning agents. In a prospective study, the influence of oral anticoagulants on intraoperative and postoperative hemorrhages in patients undergoing cataract surgery in topical anesthesia was investigated. 128 patients presenting for cataract surgery under oral anticoagulation were included. The mean preoperative prothrombin time was 39 +/- 18 %. Most patients (81 %) continued their oral anticoagulation (prothrombin time 34 +/- 13 %). All surgeries were performed in topical anesthesia. In 9 patients (7 %) an ocular hemorrhagic event was observed. These were not sight-threatening and resorbed spontaneously within a few days. Only one patient (0.8 %) had a slight hemorrhage in the anterior chamber. There were no differences (P > 0.05) between patients with or without hemorrhagic complications in the postoperative visual acuity, the intraocular pressure, the prothrombin time or the discontinuation of oral anticoagulants. Cataract surgery in topical anesthesia under oral anticoagulation did not increase the risk of sight-threatening hemorrhages. The continuation of oral anticoagulation seems particularly indicated for ambulatory cataract surgery.

What NPs need to know about anticoagulation therapy.

PubMed

Gay, Sarah E; Munaco, Sandra

2012-10-10

Venous thromboembolism (VTE) refers to pulmonary embolism and deep venous thrombosis. Anticoagulation is the cornerstone of management for patients with VTE. This review will discuss current anticoagulation guidelines.

Left Atrial Appendage Closure Device With Delivery System: A Health Technology Assessment

PubMed Central

Nevis, Immaculate; Falk, Lindsey; Wells, David; Higgins, Caroline

2017-01-01

Background Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in people with atrial fibrillation include pharmacological agents such as novel oral anticoagulants or nonpharmacological devices such as the left atrial appendage closure device with delivery system (LAAC device). The objectives of this health technology assessment were to assess the clinical effectiveness and cost-effectiveness of the LAAC device versus novel oral anticoagulants in patients without contraindications to oral anticoagulants and versus antiplatelet agents in patients with contraindications to oral anticoagulants. Methods We performed a systematic review and network meta-analysis. We also conducted an economic literature review, economic evaluation, and budget impact analysis to assess the cost-effectiveness and budget impact of the LAAC device compared with novel oral anticoagulants and oral antiplatelet agents (e.g., aspirin). We also spoke with patients to better understand their preferences, perspectives, and values. Results Seven randomized controlled studies met the inclusion criteria for indirect comparison. Five studies assessed the effectiveness of novel oral anticoagulants versus warfarin, and two studies compared the LAAC device with warfarin. No studies were identified that compared the LAAC device with aspirin in patients in whom oral anticoagulants were contraindicated. Using the random effects model, we found that the LAAC device was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR] 0.85; credible interval [Cr.I] 0.63–1.05). Similarly, the reduction in the risk of all-cause mortality was comparable between the LAAC device and novel oral anticoagulants (OR 0.71; Cr.I 0.49–1.22). The LAAC device was found to be superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45; Cr.I 0.29–0.79), whereas novel oral anticoagulants were found to be superior to the LAAC device in preventing ischemic stroke (OR 0.67; Cr.I 0.24–1.64). The body of clinical evidence was found to be of moderate quality as assed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results from the economic evaluation indicate that the LAAC device is cost-effective compared with aspirin in patients with contraindications to oral anticoagulants. In patients without contraindications to oral anticoagulants, we found that the LAAC device is not cost-effective compared with novel oral anticoagulants. Publicly funding the LAAC device in patients with nonvalvular atrial fibrillation with contraindications to oral anticoagulants could result in additional funding of $1.1 million to $7.7 million over the first five years. Patients interviewed reported on the impact of living with nonvalvular atrial fibrillation and were supportive of the LAAC device as a treatment option. Conclusions Moderate-quality evidence suggests that the LAAC device is as effective as novel oral anticoagulants in preventing stroke in people with nonvalvular atrial fibrillation. However, our results indicate that the LAAC device is cost-effective only in patients with contraindications to oral anticoagulants. People with nonvalvular atrial fibrillation with whom we spoke reported positive support for the LAAC device. PMID:28744335

Secondary poisoning of owls by anticoagulant rodenticides

USGS Publications Warehouse

Mendenhall, Vivian M.; Pank, L.F.

1980-01-01

Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

PubMed

Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

Who Were the Early Adopters of Dabigatran? An Application of Group-Based Trajectory Models

PubMed Central

Lo-Ciganic, Wei-Hsuan; Gellad, Walid F.; Huskamp, Haiden A.; Choudhry, Niteesh K.; Chang, Chung-Chou H.; Zhang, Ruoxin; Jones, Bobby L.; Guclu, Hasan; Richards-Shubik, Seth; Donohue, Julie M.

2016-01-01

BACKGROUND Variation in physician adoption of new medications is poorly understood. Traditional approaches (e.g., measuring time to first prescription) may mask substantial heterogeneity in technology adoption. OBJECTIVE Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant. METHODS A retrospective cohort study using prescribing data from IMS Xponent™ on all Pennsylvania physicians regularly prescribing anticoagulants (n=3,911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription as well as group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions. OUTCOMES Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran RESULTS We identified five distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in ≤3 months with 45% of prescriptions) and 13.4% were rapid and moderate adopters (≤3 months with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6 to 10 months post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt (odds ratio [OR] 12.2, 95%CI: 9.27–16.1) as were younger prescribers (age 36–45 years: OR 1.49, 95%CI: 1.13–1.95, age 46–55: OR 1.34, 95%CI 1.07–1.69 vs. >55 years). CONCLUSIONS Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment. PMID:27116109

Should we be looking for and treating isolated calf vein thrombosis?

PubMed

Horner, Daniel; Hogg, Kerstin; Body, Richard

2016-06-01

Management of isolated calf deep vein thrombosis is an area of significant international debate and variable clinical practice. Both therapeutic anticoagulation and conservative management carry risk. As clinical care of suspected and confirmed venous thromboembolic disease increasingly becomes the remit of emergency medicine, complex decisions are left to practising clinicians at the front door. We aim to provide a contemporary overview of recent evidence on this topic and associated challenges facing clinicians. Given the lack of high-level evidence, we present this work as a narrative review, based on structured literature review and expert opinion. A decision to manage calf thrombosis is principally dependent on the risk of complications without treatment balanced against the risks of therapeutic anticoagulation. Estimates of the former risks taken from systematic review, meta-analysis, observational cohort and recent pilot trial evidence include proximal propagation 7%-10%, pulmonary embolism 2%-3% and death <1%. Fatal bleeding with therapeutic anticoagulation stands at <0.5%, and major bleeding at approximately 2%. Estimates of haemorrhagic risk are based on robust data from large prospective management studies of venous thromboembolic disease; the risks of untreated calf deep vein thrombosis are based on small cohorts and therefore less exact. Pending further trial evidence, these risks should be discussed with patients openly, in the context of personal preference and shared decision-making. Anticoagulation may maximally benefit those patients with extensive and/or symptomatic disease or those with higher risk for complication (unprovoked, cancer-associated or pregnancy). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Randomized controlled trial of supervised patient self-testing of warfarin therapy using an internet-based expert system.

PubMed

Ryan, F; Byrne, S; O'Shea, S

2009-08-01

Increased frequency of prothrombin time testing, facilitated by patient self-testing (PST) of the International Normalized Ratio (INR) can improve the clinical outcomes of oral anticoagulation therapy (OAT). However, oversight of this type of management is often difficult and time-consuming for healthcare professionals. This study reports the first randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on OAT. A prospective, randomized controlled cross-over study was performed to test the hypothesis that supervised PST using an internet-based, direct-to-patient expert system could provide improved anticoagulation control as compared with that provided by an anticoagulation management service (AMS). During the 6 months of supervised PST, patients measured their INR at home using a portable meter and entered this result, along with other information, onto the internet web page. Patients received instant feedback from the system as to what dose to take and when the next test was due. During the routine care arm, patients attended the AMS at least every 4-6 weeks and were dosed by the anticoagulation pharmacist or physician. The primary outcome variable was the difference in the time in therapeutic range (TTR) between both arms. One hundred and sixty-two patients were enrolled (male 61.6%, mean age 58.7 years), and 132 patients (81.5%) completed both arms. TTR was significantly higher during PST management than during AMS management (median TTR 74% vs 58.6%; z=5.67, P < 0.001). The use of an internet-based, direct-to-patient expert system for the management of PST improves the control of OAT as compared with AMS management.

A review of apixaban for stroke prevention in atrial fibrillation: insights from ARISTOTLE.

PubMed

Hess, Connie N; Al-Khatib, Sana M; Granger, Christopher B; Lopes, Renato

2013-09-01

Atrial fibrillation (AF) is associated with significant mortality and morbidity, and stroke represents the most-feared complication. Consequently, AF treatment has focused on thromboprophylaxis, with warfarin as the mainstay of therapy. However, concerns over ease of use and safety have limited its use. Three novel oral anticoagulants have been approved for use in stroke prevention in AF based on randomized data: 1) dabigatran, studied in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY); 2) rivaroxaban, studied in Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF); and 3) apixaban, studied in Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). In this review, we focus on apixaban and discuss subgroup analyses that have been performed in the three trials comparing novel oral anticoagulants with warfarin. We conclude with recommendations regarding further investigations.

Clinical utility of apixaban in the prevention and treatment of venous thromboembolism: current evidence

PubMed Central

Zalpour, Ali; Oo, Thein Hlaing

2014-01-01

Anticoagulation with heparin and vitamin K antagonist has been the mainstay of prevention and treatment of venous thromboembolism (VTE) for many years. In recent years, novel oral anticoagulants such as dabigatran etexilate (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (a direct factor Xa inhibitor) have emerged for the prevention and treatment of VTE. Novel oral anticoagulants have been shown to be noninferior to vitamin K antagonist or heparin in the prevention and treatment of VTE. This review specifically examines the role of apixaban in the prevention and treatment of VTE based on the available literature. The management of apixaban in the perioperative setting is also explored because some patients on apixaban may require surgical intervention. Finally, we discuss the management of apixaban-induced major bleeding complications, the relevance of drug–drug interactions, and patient education. PMID:25395835

Review of economics and cost-effectiveness analyses of anticoagulant therapy for stroke prevention in atrial fibrillation in the US.

PubMed

von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline

2013-05-01

To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness research conducted in the real-world setting.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

PubMed

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking.

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

PubMed Central

Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-01-01

Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by combining network efficiency analysis with scoring function from molecular docking. PMID:21445339

Satisfaction with oral anticoagulants in patients with atrial fibrillation

PubMed Central

Suárez Fernández, Carmen; Castilla-Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Pose, Antonio; Montero-Pérez-Barquero, Manuel; Roquer, Jaume; Gállego, Jaime; Vivancos, José; Mostaza, Jose María

2018-01-01

Background Although, by itself, atrial fibrillation is associated with an impairment of quality of life antithrombotic therapy may play a role. Objective To evaluate the satisfaction with anticoagulant treatment in patients with nonvalvular atrial fibrillation who attended internal medicine departments in Spain. Methods Patients from two different cross-sectional studies were combined. To measure the satisfaction with anticoagulant treatment, the Anti-Clot-Treatment Scale (ACTS) questionnaire was completed by every patient. A multivariate analysis was performed to determine the variables associated with satisfaction of patients receiving oral anticoagulants. Results A total of 1,309 patients (mean age 78.5±8.4 years; 49.3% men; CHA2DS2VASC 4.9±1.5; HAS-BLED 2.0±0.9) were included in the study, of whom 902 (68.9%) were taking vitamin K antagonists (VKA) and 407 (31.1%) direct oral anticoagulants (DOACs). Overall, satisfaction with oral anticoagulation was high (ACTS Burdens scale 49.69±9.45; ACTS Benefits scale 11.35±2.61). The perceived burdens with anticoagulant treatment were lower in men, as well as in patients with no dependency, normal renal function, who were not polymedicated, or who had moderate bleeding risk. Among patients taking VKA, those subjects with a lower number of International Normalized Ratio (INR) determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden. Patients taking DOACs (vs VKA) showed a lower perceived burden with anticoagulation. Benefits with anti-coagulation were higher in men, younger patients, those with no dependency, or low bleeding risk. Perceived benefits were higher in patients taking DOACs (vs VKA). Conclusion Satisfaction with oral anticoagulation was high in patients with nonvalvular atrial fibrillation, who were attending internal medicine departments daily in Spain. Among patients taking VKA, those subjects with a lower number of INR determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden with anticoagulant therapy. Patients taking DOACs (vs VKA) showed lower perceived burdens and higher perceived benefits with anticoagulation. PMID:29497282

A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation

PubMed Central

Samsa, Greg; Matchar, David B; Dolor, Rowena J; Wiklund, Ingela; Hedner, Ewa; Wygant, Gail; Hauch, Ole; Marple, Cheryl Beadle; Edwards, Roger

2004-01-01

Background Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument – the Duke Anticoagulation Satisfaction Scale (DASS). Methods The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. Results 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78–0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. Conclusions The DASS has demonstrated reasonable psychometric properties to date. Further validation is ongoing. To the degree that dissatisfaction with anticoagulation leads to decreased adherence, poorer INR control, and poor clinical outcomes, the DASS has the potential to help identify reasons for dissatisfaction (and positive satisfaction), and thus help to develop interventions to break this cycle. As an instrument designed to be applicable across multiple models of anticoagulation management, the DASS could be crucial in the scientific comparison between those models of care. PMID:15132746

Optical profiling of anticoagulation status (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

2016-02-01

Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

Anticoagulation in pregnant women with mechanical heart valve prostheses

PubMed Central

Meschengieser, S; Fondevila, C; Santarelli, M; Lazzari, M

1999-01-01

OBJECTIVE—To evaluate the outcome of pregnancy in women with mechanical heart valve prostheses in relation to the anticoagulant treatment used in the first trimester and the incidence of thrombotic and bleeding complications.
METHODS—92 pregnancies in 59 women were followed between 1986 and 1997. In 31 pregnancies, oral anticoagulants were discontinued when pregnancy was diagnosed and subcutaneous heparin was started (12 500 U every 12 hours) adjusted to prolong the adjusted partial thromboplastin time to twice the control level. In the second trimester oral anticoagulants were resumed but changed to heparin again 15 days before the expected delivery date. In 61 pregnancies oral anticoagulants were continued during the first trimester. The same regimen of heparin was used for delivery.
RESULTS—Abortion or fetal losses were similar (p = 0.5717) in women exposed to oral anticoagulants in the first trimester (13/61; 25%) compared with those who received adjusted subcutaneous heparin (6/31; 19%). Embolic episodes were more common (p = 0.0029) in women who received heparin (4.92%) compared with those on oral anticoagulants (0.33%). Embolic episodes were cerebral and transient. No valve thromboses were observed. No malformations appeared in the 71 newborns, except for one case of hydrocephalus. There were no maternal deaths secondary to thrombotic complications. The only death was the result of major bleeding after the delivery of a premature stillborn.
CONCLUSIONS—Oral anticoagulants seem to be safer for the mother than adjusted subcutaneous heparin. Heparin does not offer a clear advantage over oral anticoagulation in the pregnancy outcome.


Keywords: pregnancy; oral anticoagulants; heparin; prosthetic valves PMID:10377303

Impact of non-anticoagulant therapy on patients with sepsis-induced disseminated intravascular coagulation: A multicenter, case-control study.

PubMed

Kudo, Daisuke; Hayakawa, Mineji; Ono, Kota; Yamakawa, Kazuma

2018-03-01

Anticoagulant therapy for patients with sepsis is not recommended in the latest Surviving Sepsis Campaign guidelines, and non-anticoagulant therapy is the global standard treatment approach at present. We aimed at elucidating the effect of non-anticoagulant therapy on patients with sepsis-induced disseminated intravascular coagulation (DIC), as evidence on this topic has remained inconclusive. Data from 3195 consecutive adult patients admitted to 42 intensive care units for the treatment of severe sepsis were retrospectively analyzed via propensity score analyses with and without multiple imputation. The primary outcome was in-hospital all-cause mortality. Among 1784 patients with sepsis-induced DIC, 745 (41.8%) were not treated with anticoagulants. The inverse probability of treatment-weighted (with and without multiple imputation) and quintile-stratified propensity score analyses (without multiple imputation) indicated a significant association between non-anticoagulant therapy and higher in-hospital all-cause mortality (odds ratio [95% confidence interval]: 1.59 [1.19-2.12], 1.32 [1.02-1.81], and 1.32 [1.03-1.69], respectively). However, quintile-stratified propensity score analyses with multiple imputation and propensity score matching analysis with and without multiple imputation did not show this association. Survival duration was not significantly different between patients in the propensity score-matched non-anticoagulant therapy group and those in the anticoagulant therapy group (Cox regression analysis with and without multiple imputation: hazard ratio [95% confidence interval]: 1.26 [1.00-1.60] and 1.22 [0.93-1.59], respectively). It remains controversial if non-anticoagulant therapy is harmful, equivalent, or beneficial compared with anticoagulant therapy in the treatment of patients with sepsis-induced DIC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinicians-related Determinants of Anticoagulation Therapy and Prophylaxis in Nigeria

PubMed Central

Anakwue, Raphael; Nwagha, Theresa; Ukpabi, Ogba J.; Obeka, Ndudim; Onwubuya, Emmanuel; Onwuchekwa, Uwa; Azubuike, Benjamin; Okoye, Innocent

2017-01-01

Background: Thromboembolic and hypercoagulable diseases are common life-threatening but treatable problems in hospital practice. Fortunately, anticoagulation is an efficacious management practice indicated for arterial, venous, and intracardiac thromboembolism. Clinicians in developing countries may have gaps in their knowledge of anticoagulation therapy/prophylaxis which could affect their clinical decision. Objectives: The study examined the knowledge and attitude of clinicians to anticoagulation therapy/prophylaxis in some tertiary hospitals in Nigeria. Methodology: The study was a multicenter survey. A pretested questionnaire was administered to clinicians in six tertiary hospitals in Southeast Nigeria. Results: A total of 528 questionnaires were returned by 419 (79.4%) residents and 109 (20.6%) consultants. We observed significant abysmal knowledge and lack of awareness of direct oral anticoagulants (DOACs) among most respondents irrespective of their job grades (P = 0.02, odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38–0.90). Their knowledge of anti-Xa assay as laboratory monitoring tool was also significantly inadequate (P = 0.001, OR 0.23, 95% CI 0.10–0.51). On statement analysis on their attitude to anticoagulation therapy/prophylaxis, “Do you think anticoagulation therapy/prophylaxis is clinically relevant” had the highest mean of 4.60, P = 0.01, and a high degree of agreement; while “Should hospital inpatient with > 3 days admission routinely receive anticoagulation/prophylaxis?” had the lowest mean of 2.27, P = 0.02, and a low degree of agreement. Conclusion: There is the need to upscale knowledge of anticoagulation agents and an attitude change to anticoagulation therapy/prophylaxis, especially on the DOACs through continuing medical education activities in emerging countries such as Nigeria. PMID:29063899

Thrombosis, Hypercoagulable States, and Anticoagulants.

PubMed

Hollenhorst, Marie A; Battinelli, Elisabeth M

2016-12-01

Patients with derangements of secondary hemostasis resulting from inherited or acquired thrombophilias are at increased risk of venous thromboemboli (VTE). Evaluation of a patient with suspected VTE proceeds via evidence-based algorithms that involve computing a pretest probability based on the history and physical examination; this guides subsequent work-up, which can include D dimer and/or imaging. Testing for hypercoagulable disorders should be pursued only in patients with VTE with an increased risk for an underlying thrombophilia. Direct oral anticoagulants are first-line VTE therapies, but they should be avoided in patients who are pregnant, have active cancer, antiphospholipid antibody syndrome, severe renal insufficiency, or prosthetic heart valves. Copyright © 2016 Elsevier Inc. All rights reserved.

Changing the strategy of balloon pulmonary angioplasty resulted in a reduced complication rate in patients with chronic thromboembolic pulmonary hypertension. A single-centre European experience.

PubMed

Kurzyna, Marcin; Darocha, Szymon; Pietura, Radosław; Pietrasik, Arkadiusz; Norwa, Justyna; Mańczak, Rafał; Wieteska, Maria; Biederman, Andrzej; Matsubara, Hiromi; Torbicki, Adam

2017-01-01

To assess the safety and efficacy of a refined balloon pulmonary angioplasty (BPA) strategy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). There were 157 BPA sessions performed in 56 CTEPH patients (47 non-operable, nine after pulmonary endarterectomy; aged 58.6 ± 17.9 years; 28 females) with severely impaired pulmonary haemodynamics (mean pulmonary artery pressure [mPAP]: 51.3 ± 12.2 mm Hg, pulmonary vascular resistance [PVR]: 10.1 ± 3.9 Wood Units). The first 50 sessions aimed to recanalise chronic occlusions and prevent reocclusion with aggressive anticoagulation. The next 107 sessions aimed to relieve "web" and "ring" lesions using reduced tip load guidewires and less intensive anticoagulation. There was significant reduction in haemoptysis (22% vs. 7%, p = 0.01), vessel injury (30% vs. 13%, p = 0.01), and reperfusion pulmonary injuries (22% vs. 4%, p = 0.01) after changing the BPA strategy. Mortality at 14 days was also reduced (6% vs. 0%; p = 0.05). The cumulative survival rate was 94.6% at 24 months after the first BPA, which was more favourable than medically treated historic controls. In the 31 patients with > 3 BPA sessions, there was significant reduction of PVR (10.3 ± 3.7 vs. 5.9 ± 2.8 Wood Units; p = 0.01), mPAP (50.7 ± 10.8 vs. 35.6 ± 9.3 mm Hg; p = 0.01) and improvement in World Health Organisation functional class (3.19 ± 0.48 vs. 1.97 ± 0.80; p < 0.001). Balloon pulmonary angioplasty improves haemodynamics and outcome but requires refined strategy to limit early complication rate.

Direct oral anticoagulants: An update.

PubMed

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[Anticoagulation in polypathological patients with atrial fibrillation].

PubMed

Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Barón-Franco, Bosco; Murcia-Zaragoza, José; Fuertes Martín, Aurelio; Alemán, Antonio; Ollero-Baturone, Manuel

2013-02-02

To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

PubMed

Hagerty, Tracy; Rich, Michael W

2017-01-01

Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

PubMed

Lanitis, T; Cotté, F E; Gaudin, A F; Kachaner, I; Kongnakorn, T; Durand-Zaleski, I

2014-08-01

To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.

Direct Oral Anticoagulants and Vitamin K Antagonists for Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Comparative Economic Evaluation

PubMed Central

Al Saleh, Abdullah S; Berrigan, Patrick; Anderson, David; Shivakumar, Sudeep

2017-01-01

Background To date, there have been few economic evaluations, from a Canadian perspective, of direct oral anticoagulants (DOACs) for the prevention of recurrent venous thromboembolism (VTE) in patients with acute unprovoked VTE. As a result, there is a lack of consensus about which treatment strategy should be adopted in the clinical setting. Objectives To assess the cost-effectiveness of currently approved anti-coagulant options, in terms of cost per quality-adjusted life-year (QALY) gained, for the prevention of recurrent VTE in patients with unprovoked events managed on an outpatient basis. Methods Microsoft Excel was used to develop a Markov model. Model parameters were determined using published literature, local hospital data, expert opinion, and chart review. The analysis considered the costs associated with pharmaceuticals, laboratory testing, hematologist fees, and treatment of recurrent VTE and major bleeding events. Effectiveness was measured in terms of QALYs, and incremental cost-effectiveness ratios (ICERs) were calculated. Results For treatment lasting 3 months, apixaban represented the most cost-effective DOAC relative to low-molecular-weight heparin (LMWH) + vitamin K antagonist, with an ICER of $7379.66. For 6 months of treatment, apixaban again represented the most cost-effective treatment, with an ICER of $84.08 per QALY gained, and this drug dominated all the other strategies at 12 months. For lifetime treatment, DOACs were unlikely to be cost-effective, given a maximum willingness to pay of $50 000 to $100 000 per QALY. In a probabilistic sensitivity analysis at 6 months, 46.4% of iterations resulted in apixaban having lower costs and better outcomes than LMWH + vitamin K antagonist, and 78.6% of iterations resulted in an ICER below $100 000 Conclusions The findings of this study suggest that apixaban is likely cost-effective for treatment durations of 3, 6, and 12 months. However, for indefinite treatment, DOACs were unlikely to be cost-effective. PMID:28680172

[Renal impairment in patients with thromboembolic event: prevalence and clinical implications. A systematic review of the literature].

PubMed

Wilke, Thomas; Wehling, Martin; Amann, Steffen; Bauersachs, Rupert M; Böttger, Björn

2015-08-01

The assessment of the renal function of patients with a deep vein thrombosis/pulmonary embolism (VTE patients) is of utmost importance for the selection/dosage of an agent in the initial anticoagulation management of these patients because the majority of available anticoagulants are cleared renally. Specifically, there is a high risk of drug accumulation and subsequent bleedings in patients with severe renal insufficiency. Consequently, specific recommendations have been made for the initial anticoagulation management of these patients in both product labels and AWMF treatment recommendations: some drugs should not be used in these patients, for other drugs a careful use, intensified screening (anti-Xa), or, in the case of enoxaparin, a dose-adjustment are recommended.This literature review aimed to answer the following questions: · What is the prevalence of renal insufficiency in VTE patients?. · Which data are available with regard to the real-world initial anticoagulation management and corresponding clinical outcomes (recurrent VTE events, bleedings, mortality) of these patients? We did a systematic review of existing publications in german or english published in 2004-2014. Only quantitative analyses have been included in the review. We identified 1,135 publications, 37 of them were included in our review. The prevalence of renal insufficiency in VTE patients, defined as CrCl < 60 ml / min, was reported to be 12.3 %-71.9 % related to all VTE patients. The prevalence of severe renal insufficiency, defined as CrCl < 30 ml / min, was reported to be 3,3 %-13,6 %. The substantial ranges in reported prevalences are mainly due to differences in the characteristics of patients addressed in the different publications.A CrCl < 30 ml / min is an independent predictor for both mortality and lethal recurrent pulmonary embolism, possibly also for severe bleedings in VTE patients. In addition to that, a severe renal insufficiency may also be a predictor for the probability that a first VTE event occurs.Several anticoagulants approved for the initial anticoagulation management of VTE patients face the risk of drug accumulation in renally insufficent patients. So, for example, a standard enoxaparin dosage was shown to be associated with elevated bleeding risk compared to adjusted enoxaparin dosage in renally insufficient patients. However, similar data do not exist for other low molecular weight heparins (LMWHs) or unfractioned heparins (UFHs). Only for two LMWHs, Certoparin and Tinzaparin, safety data with regard to renally insufficient patients have been published so far.None of the included studies showed advantages of UFH therapy in comparison to LMWH therapy in initial anticoagulation management of VTE patients. In contrast to that, available evidence shows disadvantageous efficacy/safety of UFH in comparison to LMWH treatment. However, this evidence is not based on head-to-head comparisons but is derived from registry and observational study data only. A detailed knowledge of product labels is of utmost importance in the inital anticoagulation treatment of VTE patients because several agents may not be used in the addressed patients with severe renal insufficiency at all while others may be used based on specific dosage/surveillance schemes only. We also recommend to critically appraise the current AWMF treatment guideline because it still recommends initial anticoagulation management with UFHs in VTE patients with severe renal insufficiency. Available data do not support that recommendation. © Georg Thieme Verlag KG Stuttgart · New York.

Athletes and blood clots: individualized, intermittent anticoagulation management.

PubMed

Berkowitz, J N; Moll, S

2017-06-01

Essentials Athletes on anticoagulants are typically prohibited from participation in contact sports. Short-acting anticoagulants allow for reconsideration of this precedent. An individualized pharmacokinetic/pharmacodynamics study can aid patient-specific management. Many challenges and unresolved issues exist regarding such tailored intermittent dosing. Athletes with venous thromboembolism (VTE) are typically prohibited from participating in contact sports during anticoagulation therapy, but such mandatory removal from competition can cause psychological and financial detriments for athletes and overlooks patient autonomy. The precedent of compulsory removal developed when options for anticoagulation therapy were more limited, but medical advances now allow for rethinking of the management of athletes with VTE. We propose a novel therapeutic approach to the treatment of athletes who participate in contact sports and require anticoagulation. A personalized pharmacokinetic/pharmacodynamics study of a direct oral anticoagulant can be performed for an athlete, which can inform the timing of medication dosing. Managed carefully, this can allow athletic participation when plasma drug concentration is minimal (minimizing bleeding risk) and prompt resumption of treatment after the risk of bleeding sufficiently normalizes (maximizing therapeutic time). © 2017 International Society on Thrombosis and Haemostasis.

[Treatment with inhibitors of new oral direct anticoagulants in patients with severe bleedings or urgent surgical procedures. The new dabigatran antidote: the place of idarucizumab in clinical practice].

PubMed

Boda, Zoltán

2016-03-20

Only vitamin K antagonists could be applied as oral anticoagulants over the past six decades. Coumarols have narrow therapeutic range, and unpredictable anticoagulant effects are resulted by multiple drug interactions. Therefore, regular routine monitoring of the international normalized ratio is necessary. There are two groups of factor-specific anticoagulants: molecules with anti-FIIa (dabigatran) and anti-FXa (rivaroxaban, apixaban and edoxaban) effect. Author summarizes the most important clinical features of the new oral anticoagulants, their indications and the possibilities of laboratory controls. Bleedings are the most important side effects of anticoagulants. This review summarizes the current published evidences for new oral anticoagulants reversal (non-specific and specific) agents, especially in cases with severe acute bleedings or urgent surgery procedures. It reports on how to use inhibitors, the recommended doses and the most important clinical results. The review focuses on idarucizumab - already approved by the U.S. Food and Drug Administration and the European Medicines Agency - which has a key role as the first specific inhibitor of dabigatran.

Predicting Major Bleeding in Ischemic Stroke Patients With Atrial Fibrillation.

PubMed

Hilkens, Nina A; Algra, Ale; Greving, Jacoba P

2017-11-01

Performance of risk scores for major bleeding in patients with atrial fibrillation and a previous transient ischemic attack or ischemic stroke is not well established. We aimed to validate risk scores for major bleeding in patients with atrial fibrillation treated with oral anticoagulants after cerebral ischemia and explore the net benefit of oral anticoagulants among bleeding risk categories. We analyzed 3623 patients with a history of transient ischemic attack or stroke included in the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). We assessed performance of HEMORR 2 HAGES (hepatic or renal disease, ethanol abuse, malignancy, older age, reduced platelet count or function, hypertension [uncontrolled], anemia, genetic factors, excessive fall risk, and stroke), Shireman, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and ORBIT scores (older age, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) with C statistics and calibration plots. Net benefit of oral anticoagulants was explored by comparing risk reduction in ischemic stroke with risk increase in major bleedings on warfarin. During 6922 person-years of follow-up, 266 patients experienced a major bleed (3.8 per 100 person-years). C statistics ranged from 0.62 (Shireman) to 0.67 (ATRIA). Calibration was poor for ATRIA and moderate for other models. The reduction in recurrent ischemic strokes on warfarin was larger than the increase in major bleeding risk, irrespective of bleeding risk category. Performance of prediction models for major bleeding in patients with cerebral ischemia and atrial fibrillation is modest but comparable with performance in patients with only atrial fibrillation. Bleeding risk scores cannot guide treatment decisions for oral anticoagulants but may still be useful to identify modifiable risk factors for bleeding. Clinical usefulness may be best for ORBIT, which is based on a limited number of easily obtainable variables and showed reasonable performance. © 2017 American Heart Association, Inc.

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

2017-09-01

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region.

PubMed

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region

PubMed Central

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L.; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component. PMID:28883793

Anticoagulation in Cardiobacterium hominis Prosthetic Valve Endocarditis in a Patient with Hypercoagulability: A Clinical Dilemma.

PubMed

Mamdani, Natasha; Shah, Jatan; Simms, Michael

2017-02-01

Cardiobacterium hominis is an uncommon cause of prosthetic valve endocarditis (PVE) and often presents insidiously. In comparison, prosthetic valve thrombosis (PVT) is a rare, but life-threatening condition that commonly occurs due to inadequate anticoagulation. Anticoagulation is relatively contraindicated in patients with endocarditis as it may prove to be lethal due to increased risk of cerebral hemorrhage. However, anticoagulation is required in patients with PVT, or for its prevention. We present a case of a 35-year-old male with a history of hypercoagulability and St. Jude's aortic valve on warfarin, who presented with chest pain andwas found to have a mass on the aorticvalve, with blood cultures revealing C. hominis.The patient was treated with appropriate antibiotics and anticoagulation was continued. No neurological complications were noted during the treatment period. This case demonstrates that carefully weighing the risks and benefits of continuing anticoagulation is essential in preventing poor outcomes.

Anticoagulation management associated with extracorporeal circulation.

PubMed

Sniecinski, Roman M; Levy, Jerrold H

2015-06-01

The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

PubMed

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, P<.001). Advancing age, type of OAC, health information overload and ease of OAC use (treatment expectation) were significant predictors of knowledge. Treatment expectation, including the belief that OAC treatment would cause bleeding side effects, varied significantly between participants taking warfarin and DOACs (P = .011). The study identified knowledge gaps in patients taking OACs, and these deficiencies appeared to be greater in participants taking DOACs. Knowledge assessment should be integrated into patient counselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

Ultrasound therapy in iliopsoas hematoma.

PubMed

Kaya, Basak Bilir; Icagasioglu, Afitap

2017-01-01

Warfarin is a commonly used anticoagulant agent that can have life-threatening complications, such as severe bleeding, which then require cessation of the treatment. Due to the widespread use of this therapy in recent years, incidences of its hemorrhagic complications have also increased significantly. In hemodynamically stable patients, it is possible to adopt conservative treatment strategies, such as ultrasound (US) therapy as an alternative. US is a physical therapy modality widely used in musculoskeletal disorders, but there is little evidence about its effectiveness for hemorrhagic complications because of the limited number of studies on this subject at present. A 77-year-old male who had been under oral anticoagulant therapy for 6½ years presented at the clinic with complaints of severe pain and numbness in the anterolateral thigh. US evaluation revealed iliopsoas hematoma. US treatment, administered as a physical therapy modality, resulted in faster resorption of the hematoma than expected. The patient fully recovered from clinically observed pain, meralgia paresthetica, and reduced patellar reflex.

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy

PubMed Central

Labovitz, Daniel L.; Shafner, Laura; Gil, Morayma Reyes; Virmani, Deepti; Hanina, Adam

2017-01-01

Background and Purpose This study evaluated the use of an artificial intelligence (AI) platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants (DOACs), while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. Methods A randomized, parallel-group, 12-week study was conducted in adults (n = 28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the AI Platform (intervention) or to no daily monitoring (control). The AI application visually identified the patient, the medication and confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. Results For all patients (n = 28), mean (standard deviation [SD]) age was 57 (13.2) years and 53.6% were female. Mean (SD) cumulative adherence based on the AI Platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Conclusions Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving DOACs, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on DOAC therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. PMID:28386037

Intervention targeted at nurses to improve venous thromboprophylaxis.

PubMed

Labarere, Jose; Bosson, Jean-Luc; Sevestre, Marie-Antoinette; Sellier, Elodie; Richaud, Cecile; Legagneux, Annie

2007-10-01

To assess the effectiveness of an intervention targeting both physicians and nurses vs. physicians only in improving venous thromboprophylaxis for older patients. Cluster randomized trial. Fifty hospital-based post-acute care departments in France. Patients aged 65 years or older. A multifaceted intervention to implement a clinical practice guideline addressing venous thromboprophylaxis. The effectiveness outcomes were elastic stocking use, ambulation or mobilization under the supervision of a physical therapist and anticoagulant-based prophylaxis. Patient outcomes included deep vein thrombosis and anticoagulant-related adverse events. One department allocated to the intervention targeted at physicians only and seven departments allocated to the intervention targeted at both physicians and nurses dropped out of the study. Compared with the intervention targeted at physicians only (n = 497 patients), the intervention targeted at both physicians and nurses (n = 315 patients) was associated with a higher rate of mobilization (62 vs. 37%, P < 0.001) and comparable levels of elastic stocking (32 vs. 39%, P = 0.74) and anticoagulant (55 vs. 48%, P = 0.36) use. The rates of deep vein thrombosis (15 vs. 13%, P = 0.50), bleeding (1 vs. 1%, P = 0.99) and thrombocytopaenia (0 vs. 0.2%, P = 0.99) did not differ between the two groups. A multifaceted intervention targeting nurses in addition to physicians can increase the frequency of mobilization of older patients to prevent venous thromboembolism but does not alter the use of elastic stockings and anticoagulant. A differential drop-out of departments might have contributed to creating imbalances in baseline characteristics and outcomes in this study.

Acute management of bleeding in patients on novel oral anticoagulants.

PubMed

Siegal, Deborah M; Crowther, Mark A

2013-02-01

Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopaedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over VKAs, including rapid onset, shorter half-lives, fewer drug interactions, and lack of need for routine monitoring. However, there are no established agents to reverse their anticoagulant effect. We review the risk of bleeding with the novel oral anticoagulants and the limitations of conventional coagulation assays for measuring anticoagulant effect. We provide an approach to the management of patients with bleeding complications with evidence for various interventions for reversal, where available.

Impact of a pharmacist-led warfarin self-management program on quality of life and anticoagulation control: a randomized trial.

PubMed

Verret, Lucie; Couturier, Justine; Rozon, Andréanne; Saudrais-Janecek, Sarah; St-Onge, Amélie; Nguyen, Angela; Basmadjian, Arsène; Tremblay, Simon; Brouillette, Denis; de Denus, Simon

2012-10-01

To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic. Prospective, randomized, controlled, open-label trial. Tertiary care academic medical center. A total of 114 patients aged 18-75 years who were followed at a specialized anticoagulation clinic, had received warfarin for at least 6 months, and were expected to continue warfarin for a minimum of 4 months. All patients attended an educational session on anticoagulation provided by a pharmacist. Patients randomized to the self-management group (58 patients) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm. Patients in the control group (56 patients) continued to undergo standard management at the anticoagulation clinic. Patients completed a validated quality-of-life questionnaire and the validated Oral Anticoagulation Knowledge test at the beginning and end of the study. The quality of anticoagulation control was evaluated by using the time spent in therapeutic range. After 4 months of follow-up, a significant improvement in the self-management group was observed compared with the control group in four of the five quality-of-life topics (p<0.05). Improvements in knowledge were observed in both groups after the training session and persisted after 4 months (p<0.05 for all). The time spent in the therapeutic range (80.0% in the self-management group vs 75% in the control group, p=0.79) and in the extended therapeutic range ([target international normalized ratio ± 0.3] 93.2% in the self-management group vs 91.1% in the control group, p=0.30) were similar between groups. A self-management warfarin program led by pharmacists resulted in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring, while maintaining a level of anticoagulation control similar to a high-quality specialized anticoagulation clinic. © 2012 Pharmacotherapy Publications, Inc.

Impact of Anticoagulation in Elderly Patients With Pulmonary Embolism That Undergo IVC Filter Placement: A Retrospective Cohort Study.

PubMed

Falatko, John M; Dalal, Bhavinkumar; Qu, Lihua

2017-12-01

Anticoagulation is the primary treatment for pulmonary embolism (PE). Inferior vena cava (IVC) filters are an adjunctive intervention to prevent recurrent pulmonary embolism. Long-term outcomes in elderly patients with contraindications to anticoagulation after IVC filter placement for prevention of recurrent pulmonary embolism have yet to be assessed. Patients ≥60years of age, that had an IVC filter placed between 1 January, 2008 and 2 February, 2013, with a primary diagnosis of pulmonary embolism, were included. Patients that died during index hospitalisation, were discharged to hospice, or had active malignancy were excluded. The primary endpoint was overall survival. Patients were divided depending on whether they were treated with an approved anticoagulant for VTE or had no anticoagulant. Of the 152 patients identified, 55 were not anti-coagulated after IVC filter placement. The incidence of death was 0.4 per 1000 filter days and 0.7 per 1000 filter days in the anti-coagulated and untreated groups respectively (p-value=0.06). After statistical correction for co-morbid conditions, the effect of anticoagulation was not significant (HR 0.82 CI 0.49-1.37, p-value 0.46). Age was a significant confounder that was associated with death. Increased BMI was protective. Indications for IVC filter placement were numerous, but similar between the two groups. Treatment with an approved anticoagulant is recommended after IVC filter placement for prevention of recurrent PE, however its effect may be attenuated by advanced age. In elderly patients that have undergone IVC filter placement for prevention of recurrent PE, survival may be more dependent on age and co-morbid conditions than exposure to anticoagulation. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation.

PubMed

Königsbrügge, Oliver; Weigel, Günter; Quehenberger, Peter; Pabinger, Ingrid; Ay, Cihan

2018-02-07

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.

Potential use of NOACs in developing countries: pros and cons.

PubMed

Bista, Durga; Chalmers, Leanne; Bereznicki, Luke; Peterson, Gregory

2014-07-01

Although vitamin K antagonists (VKAs) are effective for long-term thromboprophylaxis in atrial fibrillation (AF), their limitations have led to widespread underutilisation, especially in the developing world. Novel oral anticoagulants (NOACs) have emerged as promising alternatives to VKAs, although there are some particular considerations and challenges to their introduction in developing countries. This review summarises the current state of antithrombotic management of AF in the developing world, explores the early evidence for the NOACs and describes some of the special considerations that must be taken into account when considering the role of the NOACs within developing countries' health care systems. A literature search was conducted via PubMed and Google Scholar to find articles published in English between the years 2000 to 2014. Search terms used were "atrial fibrillation", "oral anticoagulants", "warfarin", "NOACs", "dabigatran", "rivaroxaban", "apixaban", "edoxaban", "time in therapeutic range", "International Normalized Ratio" "cost-effectiveness", "stroke", "adverse-drug reactions" and "drug-drug interactions", together with the individual names of developing countries as listed by the World Bank. We reviewed the results of randomized clinical trials, relevant retrospective and prospective studies, case-studies and review articles. Many developing countries lack or have sporadic data on the quality of AF management, making it difficult to anticipate the potential impact of NOACs in these settings. The utilisation of anticoagulants for AF appears highly variable in developing countries. Given the issues associated with VKA therapy in many developing countries, NOACs offer some potential advantages; however, there is insufficient evidence to advocate the widespread replacement of warfarin at present. VKAs may continue to have a role in selected patients or countries, especially if alternative monitoring strategies can be utilised. The evaluation of the introduction of NOACs should consider safety, budget concerns and the quality of oral anticoagulation care achieved by each country. Prospective registries will be important in developing countries to better elucidate the comparative safety, efficacy and cost-effectiveness of NOACs and VKAs as NOACs are introduced into practice.

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. Discussion To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. Trial registration Eudra CT. Identifier: 2009-016643-18. PMID:23237631

Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve anticoagulant ability and endothelial cell compatibility.

PubMed

Liao, Yuzhen; Li, Linhua; Chen, Jiang; Yang, Ping; Zhao, Ansha; Sun, Hong; Huang, Nan

2017-07-01

Surfaces with dual functions that simultaneously exhibit good anticoagulant ability and endothelial cell (EC) compatibility are desirable for blood contact materials. However, these dual functions have rarely been achieved by inorganic materials. In this study, titanium dioxide (TiO 2 ) films were treated by sulphuric acid (H 2 SO 4 ) and ultraviolet (UV) irradiation successively (TiO 2 H 2 SO 4 -UV), resulting in good anticoagulant ability and EC compatibility simultaneously. We found that UV irradiation improved the anticoagulant ability of TiO 2 films significantly while enhancing EC compatibility, though not significantly. The enhanced anticoagulant ability could be related to the oxidation of surface-adsorbed hydrocarbons and increased hydrophilicity. The H 2 SO 4 treatment improved the anticoagulant ability of TiO 2 films slightly, while UV irradiation improved the anticoagulant ability strongly. The enhanced EC compatibility could be related to the increased surface roughness and positive charges on the surface of the TiO 2 films. Furthermore, the time-dependent degradation of the enhanced EC compatibility and anticoagulant ability of TiO 2 H 2 SO 4 -UV was observed. In summary, TiO 2 H 2 SO 4 -UV expressed both excellent anticoagulant ability and good EC compatibility at the same time, which could be desirable for blood contact materials. However, the compatibility of TiO 2 H 2 SO 4 -UV with smooth muscle cells (SMCs) and macrophages was also improved. More effort is still needed to selectively improve EC compatibility on TiO 2 films for better re-endothelialization. Copyright © 2017 Elsevier B.V. All rights reserved.

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

PubMed

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

Evaluation of US prescription patterns: Are treatment guidelines for cancer-associated venous thromboembolism being followed?

PubMed

Khorana, Alok A; Yannicelli, Daniel; McCrae, Keith R; Milentijevic, Dejan; Crivera, Concetta; Nelson, Winnie W; Schein, Jeffrey R

2016-09-01

Venous thromboembolism (VTE) is a common complication of cancer. Clinical practice guidelines recommend low-molecular-weight heparin (LMWH) for treatment of cancer-associated VTE, but it is unclear how frequently these are followed. This study assessed anticoagulation treatment patterns for VTE in newly diagnosed cancer patients in the United States. MarketScan® claims records of more than 80 million insured members between January 1, 2009 and July 31, 2014 were retrospectively analyzed. Subjects were included if they were 18years of age or older, and had a diagnosis of cancer (9 solid tumor types) and VTE. Data were included for LMWH, warfarin, and other anticoagulants (fondaparinux and direct oral anticoagulants [DOACs]). Patients with anticoagulant treatment prior to cancer diagnosis were excluded. VTE developed in 6.2% of cancer patients (median, 181days after cancer diagnosis). VTE rates were highest for pancreatic (17.5%) and lung (12.6%) cancer and lowest for breast (4.2%) and prostate (4.1%) cancer. For patients for whom outpatient prescription data were available, warfarin was most commonly used (50.0%), followed by LMWH (40.0%) and other anticoagulants (10.0%). Over 6months, 13% of patients who initiated injectable anticoagulants remained on them compared with 30% of those who initiated oral anticoagulants. More patients switched from LMWH to warfarin and other anticoagulants (44%) versus those who switched from warfarin (28%). Warfarin was the most utilized anticoagulant for cancer-associated VTE despite guideline recommendations for LMWH. More patients remained on oral versus injectable agents, which may be related to self-injection burden and costs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

[The current role of warfarin].

PubMed

Michalcová, Jana; Buliková, Alena; Zavřelová, Jiřina; Prudková, Marie; Penka, Miroslav

Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.

Isolation and characterization of an anticoagulant present in the salivary glands of the bont-legged tick, Hyalomma truncatum.

PubMed

Joubert, A M; Crause, J C; Gaspar, A R; Clarke, F C; Spickett, A M; Neitz, A W

1995-02-01

A low molecular mass anticoagulant (17 kDa) was isolated from the salivary glands of prefed female Hyalomma truncatum ticks by means of reverse phase and anion-exchange HPLC. Trypsin digestion and amino acid analysis confirmed the protein nature of the anticoagulant. The inhibitor appears to be uncompetitive with a Ki of 6.9 x 10(-10)M. The target of the anticoagulant is factor Xa at the junction of the extrinsic and intrinsic pathways. This may be crucial for the survival of the tick, making it feasible to investigate the possibility of vaccination with this antihaemostatic against tick feeding. In addition, tick anticoagulants may possibly have therapeutic application in controlling thrombosis.

Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens.

PubMed

Herishanu, Yair; Misgav, Mudi; Kirgner, Ilya; Ben-Tal, Ofira; Eldor, Amiram; Naparstek, Ella

2004-07-01

Treatment with intensive chemotherapy regimens is frequently complicated by severe thrombocytopenia. During the period of severe thrombocytopenia, anticoagulant treatment is not uncommonly indicated for thromboembolic events or thromboprophylaxis in these patients. We report 10 hematological patients treated with intensive chemotherapy protocols that were anticoagulated with enoxaparin for catheter related central venous thrombosis and thromboprophylaxis. During the period of severe thrombocytopenia the dosages of enoxaparin were reduced and no major bleeding occurred. Based on our experience we suggest that reduced dosages of low molecular weight heparins may be used relatively safely during transient severe thrombocytopenia.

Prevention of thromboembolic events in patients with atrial fibrillation - new anticoagulants.

PubMed

Campos, Alexandre Holthausen; Cirenza, Cláudio

2011-09-01

The authors present alternatives for the treatment of cardiac arrhythmias. Its detection is based on the use of different methods that record the cardiac electrical activity. The treatment involves intervening in the underlying disorder, antiarrhythmic drugs, stimulation and cardiac defibrillation devices, and, less often, surgery. The technological advances in the last two decades have provided greater efficiency in diagnoses and therapy. Atrial fibrilation patients will benefit from a new set of anticoagulant drugs tested in the past three years. The potential advantages include greater safety and efficacy, as well as convenience for not requiring frequent laboratory controls.

Consensus recommendations for preventing and managing bleeding complications associated with novel oral anticoagulants in singapore.

PubMed

Ng, Heng Joo; Chee, Yen Lin; Ponnudurai, Kuperan; Lim, Lay Cheng; Tan, Daryl; Tay, Jam Chin; Handa, Pankaj Kumar; Akbar Ali, Mufeedha; Lee, Lai Heng

2013-11-01

Novel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished. A working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified. The NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of <30 mLs/min. Meticulous consideration of risk versus benefits should be exercised before starting a patient on a NOAC. In patients presenting with bleeding, risk stratification of the severity of bleeding as well as identification of the source of bleeding should be performed. In life-threatening bleeds, recombinant activated factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required. NOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

Cardioembolic Stroke

PubMed Central

Kamel, Hooman; Healey, Jeff S.

2017-01-01

Cardiac embolism accounts for an increasing proportion of ischemic strokes, and might multiply several-fold over the next decades. However, research points to several potential strategies to stem this expected rise in cardioembolic stroke. First, although one-third of strokes are of unclear cause, it is increasingly accepted that many of these cryptogenic strokes arise from a distant embolism rather than in-situ cerebrovascular disease, leading to the recent formulation of “embolic stroke of undetermined source” (ESUS) as a distinct target for investigation. Second, recent clinical trials have indicated that ESUS may often stem from subclinical atrial fibrillation (AF) which can be diagnosed with prolonged heart-rhythm monitoring. Third, emerging evidence indicates that a thrombogenic atrial substrate can lead to atrial thromboembolism even in the absence of AF. Such an atrial cardiopathy may explain many cases of ESUS, and oral anticoagulant drugs may prove to reduce stroke risk from atrial cardiopathy given its parallels to AF. Non-vitamin K antagonist oral anticoagulant (NOAC) drugs have recently expanded therapeutic options for preventing cardioembolic stroke and are currently being tested for stroke prevention in patients with ESUS, including specifically those with atrial cardiopathy. Fourth, increasing appreciation of thrombogenic atrial substrate and the common co-existence of cardiac and extra-cardiac stroke risk factors suggests benefits from global vascular risk factor management in addition to anticoagulation. Finally, improved imaging of ventricular thrombus plus the availability of NOAC drugs may lead to better prevention of stroke from acute myocardial infarction and heart failure. PMID:28154101

Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain.

PubMed

Narouze, Samer; Benzon, Honorio T; Provenzano, David A; Buvanendran, Asokumar; De Andres, José; Deer, Timothy R; Rauck, Richard; Huntoon, Marc A

2015-01-01

Interventional spine and pain procedures cover a far broader spectrum than those for regional anesthesia, reflecting diverse targets and goals. When surveyed, interventional pain and spine physicians attending the American Society of Regional Anesthesia and Pain Medicine (ASRA) 11th Annual Pain Medicine Meeting exhorted that existing ASRA guidelines for regional anesthesia in patients on antiplatelet and anticoagulant medications were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors necessitated separate guidelines for pain and spine procedures. In response, ASRA formed a guidelines committee. After preliminary review of published complication reports and studies, committee members stratified interventional spine and pain procedures according to potential bleeding risk as low-, intermediate-, and high-risk procedures. The ASRA guidelines were deemed largely appropriate for the low- and intermediate-risk categories, but it was agreed that the high-risk targets required an intensive look at issues specific to patient safety and optimal outcomes in pain medicine. The latest evidence was sought through extensive database search strategies and the recommendations were evidence-based when available and pharmacology-driven otherwise. We could not provide strength and grading of these recommendations as there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations.

Anticoagulation management in the ambulatory surgical setting.

PubMed

Eisenstein, Diana Hill

2012-04-01

Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Outpatient management of oral vitamin K antagonist therapy: defining and measuring high-quality management.

PubMed

Phillips, Katherine W; Ansell, Jack

2008-01-01

Oral anticoagulation therapy with warfarin is the mainstay of prevention and treatment of thromboembolic disease. However, it remains one of the leading causes of harmful medication errors and medication-related adverse events. The beneficial outcomes of oral anticoagulation therapy are directly dependent upon the quality of dose and anticoagulation management, but the literature is not robust with regards to what constitutes such management. This review focuses on, and attempts to define, the parameters of high-quality anticoagulation management and identifies the appropriate outcome measures constituting high-quality management. Elements discussed include the most fundamental measure, time in therapeutic range, along with other parameters including therapy initiation, time to therapeutic range, dosing management when patients are not in therapeutic range, perioperative dosing management, patient education, and other important outcome measures. Healthcare providers who manage oral anticoagulation therapy should utilize these parameters as a measure of their performance in an effort to achieve high-quality anticoagulation management.

[The study of anticoagulants selection in platelet-rich plasma preparation].

PubMed

Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

2015-07-01

To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Assessing Bleeding Risk in Patients Taking Anticoagulants

PubMed Central

Shoeb, Marwa; Fang, Margaret C.

2013-01-01

Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

PubMed

Kang, Jieun; Kim, Seon Ok; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

2018-05-17

Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants.

PubMed

Yanagisawa, Naohiro; Nagata, Naoyoshi; Watanabe, Kazuhiro; Iida, Tatsuhiro; Hamada, Mariko; Kobayashi, Sakurako; Shimbo, Takuro; Akiyama, Junichi; Uemura, Naomi

2018-04-14

To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants (DOAC). We collected data from 218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics (age- and sex-matched controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB. PPB rate was significantly higher in warfarin users and DOAC users compared with controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group (guideline recommendation) had a higher PPB rate (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group. PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

Non anti-coagulant factors associated with filter life in continuous renal replacement therapy (CRRT): a systematic review and meta-analysis.

PubMed

Brain, Matthew; Winson, Elizabeth; Roodenburg, Owen; McNeil, John

2017-02-20

Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis. A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29 th February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life. Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical ventilation, elevated SOFA or LOD score, elevations in ionized calcium, elevated platelet count, red cell transfusion, platelet factor 4 (PF-4) antibodies, and elevated fibrinogen. Majority of studies are observational or report circuit factors in sub-analysis. Risk of bias is high and findings require targeted investigations to confirm. The interaction of patient, pathology, anticoagulation, vascular access, circuit and staff factors contribute to CRRT filter life. There remains an ambiguity from published data as to which site and side should be the first choice for vascular access placement and what interaction this has with patient factors and timing. Early consideration of tunnelled semi-permanent access may provide optimal filter life if longer periods of CRRT are anticipated. There remains an absence of robust evidence outside of anti-coagulation strategies despite over 20 years of therapy delivery however trends favour CVVHD-F over CVVH.

Impact of self-funding on patient experience of oral anticoagulation self-monitoring: a qualitative study

PubMed Central

Tompson, Alice; Heneghan, Carl; Sutton, Stephen; Fitzmaurice, David; Ward, Alison

2016-01-01

Objective To explore the impact self-funding has on patient experience of oral anticoagulation therapy self-monitoring. Design Semistructured, qualitative interviews were conducted. Transcripts were analysed thematically using constant comparison. Setting England. Participants Interviewees were participants of the Cohort Study of Anticoagulation Self-Monitoring (CASM). Cohort members were recruited as they bought a monitor from the major manufacturer in the UK. A purposive sample was invited to be interviewed on completion of the 12-month cohort follow-up. Data Patient narratives on their experiences of self-monitoring their oral anticoagulation therapy in non-trial conditions. Results 26 interviews were completed. Interviewees viewed purchasing the monitoring device as a long-term commitment balancing the limitations of clinic-based monitoring against the cost. They were unable to try out the monitor prior to purchase and therefore had to be confident in their own ability to use it. The variable provision of self-monitoring equipment caused resentment, and interviewees were uncomfortable negotiating with healthcare professionals. High test strip usage while learning how to use the monitor caused anxiety that was exacerbated by worries about their cost. However, self-funding did mean that interviewees felt a sense of ownership and were determined to persevere to overcome problems. Conclusions Self-funding has negative implications in terms of equity of access; however, the money invested acts as a barrier to discontinuation. If oral anticoagulation therapy self-monitoring devices and consumables were provided free of charge in routine care, the training and support available in England may need to be reviewed to prevent discontinuation rates rising to those observed in clinical trials. PMID:28011812

A functional and thromboelastometric-based micromethod for assessing crotoxin anticoagulant activity and antiserum relative potency against Crotalus durissus terrificus venom.

PubMed

Prezoto, B C; Tanaka-Azevedo, A M; Marcelino, J R; Tashima, A K; Nishiduka, E S; Kapronezai, J; Mota, J O; Rocha, M M T; Serino-Silva, C; Oguiura, N

2018-06-15

The assessment of the capacity of antivenoms to neutralize the lethal activity of snake venoms still relies on traditional rodent in vivo lethality assay. ED 50 and LD 50 assays require large quantities of venoms and antivenoms, and besides leading to animal suffering. Therefore, in vitro tests should be introduced for assessing antivenom neutralizing capacity in intermediary steps of antivenom production. This task is facilitated when one key lethal toxin is identified. A good example is crotoxin, a β-neurotoxin phospholipase A 2 -like toxin that presents anticoagulant activity in vitro and is responsible for the lethality of venoms of Crotalus durissus snakes. By using rotational thromboelastometry, we reported recently one sensitive coagulation assay for assessing relative potency of the anti-bothropic serum in neutralizing procoagulant activity of Bothrops jararaca venom upon recalcified factor-XII-deficient chicken plasma samples (CPS). In this study, we stablished conditions for determining relative potency of four batches of the anti-crotalic serum (ACS) (antagonist) in inactivating crotoxin anticoagulant activity in CPS (target) simultaneously treated with one classical activator of coagulation (agonists). The correlation coefficient (r) between values related the ACS potency in inactivating both in vitro crotoxin anticoagulant activity and the in vivo lethality of whole venom (ED 50 ) was 0.94 (p value < 0.05). In conclusion, slowness in spontaneous thrombin/fibrin generation even after recalcification elicit time lapse sufficient for elaboration of one dose-response curve to pro- or anti-coagulant agonists in CPS. We propose this methodology as an alternative and sensitive assay for assessing antivenom neutralizing ability in plasma of immunized horses as well as for in-process quality control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

PubMed

Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

2017-10-12

Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

PubMed

Flaker, Greg C; Gruber, Michael; Connolly, Stuart J; Goldman, Steven; Chaparro, Sandra; Vahanian, Alec; Halinen, Matti O; Horrow, Jay; Halperin, Jonathan L

2006-11-01

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation.

PubMed

Manzano-Fernández, Sergio; Andreu-Cayuelas, José M; Marín, Francisco; Orenes-Piñero, Esteban; Gallego, Pilar; Valdés, Mariano; Vicente, Vicente; Lip, Gregory Y H; Roldán, Vanessa

2015-06-01

New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

PubMed

Shim, Choong Nam; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Ha Yan; Kim, Dong Wook; Lee, Hyuk

2016-01-01

The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.

Health literacy and warfarin therapy at two anticoagulation clinics in Brazil

PubMed Central

Martins, Maria Auxiliadora Parreiras; Costa, Josiane Moreira; Mambrini, Juliana Vaz de Melo; Ribeiro, Antonio Luiz Pinho; Benjamin, Emelia J; Brant, Luisa Campos Caldeira; Paasche-Orlow, Michael K; Magnani, Jared W

2017-01-01

Objective Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. Methods We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015–2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. Results We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0–14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman’s coefficient 0.02; p=0.70). Conclusions Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. PMID:28258243

Health literacy and warfarin therapy at two anticoagulation clinics in Brazil.

PubMed

Martins, Maria Auxiliadora Parreiras; Costa, Josiane Moreira; Mambrini, Juliana Vaz de Melo; Ribeiro, Antonio Luiz Pinho; Benjamin, Emelia J; Brant, Luisa Campos Caldeira; Paasche-Orlow, Michael K; Magnani, Jared W

2017-07-01

Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015-2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0-14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman's coefficient 0.02; p=0.70). Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Managing the therapeutic dilemma: patients with spontaneous intracerebral hemorrhage and urgent need for anticoagulation.

PubMed

Bertram, M; Bonsanto, M; Hacke, W; Schwab, S

2000-03-01

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.

Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex.

PubMed

Kapoor, Karan; McGill, Nicole; Peterson, Cynthia B; Meyers, Harold V; Blackburn, Michael N; Baudry, Jerome

2016-03-28

The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches.

Anticoagulation Quality Assessment in Patients with Nonvalvular Atrial Fibrillation (NVAF) and Comparison with Major Trials of Direct-Acting Oral Anticoagulants

DTIC Science & Technology

2016-04-22

Purpose: The benefits of warfarin anticoagulation therapy are strongly correlated with the ability to maintain patients’ INR goal, known as the time...Rosendaal). Differences in TTR calculations could alter perceptions about the effectiveness of warfarin therapy.

Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenbaum, R.C.; Johnston, G.S.; Whitley, N.O.

1986-02-01

The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.

Breast hematoma complicating anticoagulant therapy: management and literature review.

PubMed

Salemis, Nikolaos S

2012-01-01

Anticoagulant-induced spontaneous breast hematoma is a very rare clinical entity with only a few cases reported in the literature so far. We describe a case of a spontaneous breast hematoma in a female patient under combined oral anticoagulant and antiplatelet therapy. Physicians should be aware of this possibility in patients under anticoagulant treatment presenting with sudden onset of breast pain and a palpable mass. Repeat imaging is mandatory until complete clinical and imaging resolution of the hematoma. If an abnormality persists, further investigation is needed to exclude an underlying malignancy.

Stroke prevention in the elderly atrial fibrillation patient with comorbid conditions: focus on non-vitamin K antagonist oral anticoagulants

PubMed Central

Turagam, Mohit K; Velagapudi, Poonam; Flaker, Greg C

2015-01-01

Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed. PMID:26366064

Anticoagulant therapy: basic principles, classic approaches and recent developments.

PubMed

Sinauridze, Elena I; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

2012-09-01

The standard multipotent anticoagulants (unfractionated and low molecular weight heparins, antagonists of vitamin K) are commonly used for treatment and/or prophylaxis of different thrombotic complications, such as deep vein thrombosis, thrombophilia, pulmonary embolism, myocardial infarction, stroke and so on. Advantages and shortcomings of these anticoagulants are considered. The modern tendencies to use small selective direct inhibitors of thrombin or factor Xa are surveyed. The search of the new targets in the coagulation cascade for development of new promising anticoagulants and improvement in antithrombotic therapy is discussed.

Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

PubMed

Hasan, Syed Shahzad; Kow, Chia Siang; Curley, Louise E; Baines, Darrin L; Babar, Zaheer-Ud-Din

2018-05-09

Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. Areas covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. Expert commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

PubMed

van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

2002-11-20

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Pooled analysis of patient-level data from 6 published, randomized clinical trials. A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.

Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow.

PubMed

Sobczynski, Daniel J; Eniola-Adefeso, Omolola

2017-01-15

Plasma proteins rapidly coat the surfaces of particulate drug carriers to form a protein corona upon their injection into the bloodstream. The high presence of immunoglobulins in the corona formed on poly(lactic-co-glycolic acid) (PLGA) vascular-targeted carrier (VTC) surfaces was recently shown to negatively impact their adhesion to activated endothelial cells (aECs) in vitro. Here, we characterized the influence of anticoagulants, or their absence, on the binding efficiency of VTCs of various materials via modulation of their protein corona. Specifically, we evaluated the adhesion of PLGA, poly(lactic acid) (PLA), polycaprolactone (PCL), silica, and polystyrene VTCs to aECs in heparinized, citrated, and non-anticoagulated (serum and whole) blood flows relative to buffer control. Particle adhesion is substantially reduced in non-anticoagulated blood flows regardless of the material type while only moderate to minimal reduction is observed for VTCs in anticoagulant-containing blood flow depending on the anticoagulant and material type. The substantial reduction in VTC adhesion in blood flows was linked to a high presence of immunoglobulin-sized proteins in the VTC corona via SDS-PAGE analysis. Of all the materials evaluated, PLGA was the most sensitive to plasma protein effects while PCL was the most resistant, suggesting particle hydrophobicity is a critical component of the observed negative plasma protein effects. Overall, this work demonstrates that anticoagulant positively alters the effect of plasma proteins in prescribing VTC adhesion to aECs in human blood flow, which has implication in the use of in vitro blood flow assays for functional evaluation of VTCs for in vivo use. This study addresses the impact of anticoagulant on altering the extent of the previously observed protein corona-induced adhesion reduction of vascular-targeted drug carriers in human blood flows. Specifically, serum blood flow (no anticoagulant) magnifies the negative effect of the plasma protein corona on drug carrier adhesion relative to citrated or heparinized blood flows. Overall, the results from this work suggest that serum better predicts targeted drug carrier adhesion efficiency in vivo compared to anticoagulant containing plasma. Furthermore, this study offers critical insight into the importance of how the choice of anticoagulant can greatly affect drug delivery-related processes in vitro. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Extended International Normalized Ratio testing intervals for warfarin-treated patients.

PubMed

Barnes, G D; Kong, X; Cole, D; Haymart, B; Kline-Rogers, E; Almany, S; Dahu, M; Ekola, M; Kaatz, S; Kozlowski, J; Froehlich, J B

2018-05-15

Essentials Warfarin typically requires International Normalized Ratio (INR) testing at least every 4 weeks. We implemented extended INR testing for stable warfarin patients in six anticoagulation clinics. Use of extended INR testing increased from 41.8% to 69.3% over the 3 year study. Use of extended INR testing appeared safe and effective. Background A previous single-center randomized trial suggested that patients with stable International Normalized Ratio (INR) values could safely receive INR testing as infrequently as every 12 weeks. Objective To test the success of implementation of an extended INR testing interval for stable warfarin patients in a practice-based, multicenter collaborative of anticoagulation clinics. Methods At six anticoagulation clinics, patients were identified as being eligible for extended INR testing on the basis of prior INR value stability and minimal warfarin dose changes between 2014 and 2016. We assessed the frequency with which anticoagulation clinic providers recommended an extended INR testing interval (> 5 weeks) to eligible patients. We also explored safety outcomes for eligible patients, including next INR values, bleeding events, and emergency department visits. Results At least one eligible period for extended INR testing was identified in 890 of 3362 (26.5%) warfarin-treated patients. Overall, the use of extended INR testing in eligible patients increased from 41.8% in the first quarter of 2014 to 69.3% in the fourth quarter of 2016. The number of subsequent out-of-range next INR values were similar between eligible patients who did and did not have an extended INR testing interval (27.3% versus 28.4%, respectively). The numbers of major bleeding events were not different between the two groups, but rates of clinically relevant non-major bleeding (0.02 per 100 patient-years versus 0.09 per 100 patient-years) and emergency department visits (0.07 per 100 patient-years versus 0.19 per 100 patient-years) were lower for eligible patients with extended INR testing intervals than for those with non-extended INR testing intervals. Conclusions Extended INR testing for stable warfarin patients can be successfully and safely implemented in diverse, practice-based anticoagulation clinic settings. © 2018 International Society on Thrombosis and Haemostasis.

A new therapeutic strategy for electrical cardioversion of atrial fibrillation.

PubMed

de Luca, I; Sorino, M; Del Salvatore, B; de Luca, L

2001-11-01

The conventional approach to cardioversion of atrial fibrillation includes a period of anticoagulation with oral anticoagulant therapy (OAT) extending from 3 weeks precardioversion to 4 weeks postcardioversion. The protocol of rapid anticoagulation (such as that of the ACUTE study) consists of a precardioversion transesophageal echocardiography (TEE) followed by OAT for 4 weeks. In the last few years low-molecular-weight heparins have established themselves as a safe and efficacious alternative to traditional antithrombotic therapies. The aim of this study was to demonstrate that the exclusion of thrombi by precardioversion TEE together with the exclusion of atrial stunning by a second TEE performed after 1 week, to date not suggested in the literature, could reduce to 7 days the period of pericardioversion anticoagulation. This therapy would be carried out using low-molecular-weight heparins with no need for biological monitoring and with the possibility of self-administration. We have studied 57 consecutive patients who had atrial fibrillation or flutter with a history of atrial fibrillation lasting > 48 hours. All patients received enoxaparin at a dosage of 100 IU antiXa/kg twice daily before undergoing multiplane TEE. Previous informed consent and ethical committee authorization had been obtained. Twenty-four hours following TEE, in the absence of thrombi and/or spontaneous moderate/severe echocontrast in the atrial chambers, the patients underwent electrical cardioversion and were discharged within 24 hours of sinus rhythm restoration. These patients were prescribed enoxaparin at the indicated dosage twice daily until TEE, performed in an outpatients setting 7 days following cardioversion. In the absence of thrombi and/or atrial and/or left atrial appendage stunning, OAT was terminated. Enoxaparin was associated with OAT for the following 3 weeks if any of the following signs of stunning were present: A wave inferior to the normal value for age at transmitral Doppler; a left atrial appendage emptying velocity < 40 cm/s; the appearance or increase in the severity of spontaneous echocontrast. For all patients, clinical and electrocardiographic follow-up was carried out at 1 month. In one patient TEE was not tolerated and one refused it. In 7 patients cardioversion was not performed: 4 because of the presence of thrombi, 1 because of moderate/severe spontaneous echocontrast and 2 owing to spontaneous cardioversion. Of the remaining 48 patients, cardioversion proved to be efficacious in 38, with sustained sinus rhythm at 1 week in 33 patients. One of these refused the second TEE and of the remaining 32 patients, 24 (75%) showed no signs of stunning at the second TEE and so anticoagulation was terminated. Thus, after 1 week, 75% (24/33) of patients in sinus rhythm could benefit from a shortened anticoagulation therapy which lasted for a mean of only 8.5 days. No patients showed signs of a thromboembolic accident at 1 and 2 months of follow-up. Most patients undergoing electrical cardioversion for atrial fibrillation could benefit from a shorter period of anticoagulation with low-molecular-weight heparins for 1 week if TEE precardioversion and 7 days postcardioversion excludes thrombi and atrial stunning. The management of patients with atrial fibrillation would be greatly simplified.

Dielectric permittivity change detects the process of blood coagulation: Comparative study of dielectric coagulometry with rotational thromboelastometry.

PubMed

Otaki, Yoichi; Ebana, Yusuke; Yoshikawa, Shunji; Isobe, Mitsuaki

2016-09-01

Intravascular thrombus formation causes various cardiovascular diseases. To monitor coagulation is important for screening native status, prevention from bleeding and maintaining it within its therapeutic range. The prothrombin time and the activated partial thromboplastin time are widely used for assessment and recognized as the conventional methods. Prothrombin time methods employ enhancement of coagulation with thromboplastin. Since the laboratory data depend on the production lot and/or the manufacturer, the accurate methods are required for evaluation. Rotational thromboelastometry (ROTEM) is a method based on detection of the change in resistance to rotational movement during blood clotting, while dielectric blood coagulometry (DBCM) is a novel method for assessment of clotting by measuring the change of electrical permittivity. These methods are thus based on the technology for observation of different physical phenomena. The aim of this study was to compare parameters such as the clotting time obtained by ROTEM and DBCM to evaluate their clinical usefulness. ROTEM and DBCM parameters were measured in 128 patients. The ROTEM clotting time showed a significant positive correlation with the DBCM coagulation time (R=0.707, p<0.001). Comparison of the DBCM coagulation time between patients with and without anticoagulant therapy (including novel oral anticoagulants) revealed a significant difference (43.8±11.9min in the anticoagulant group vs 29.4±8.3min in the control group, p<0.001). Evaluation of coagulation was equivalent with DBCM and ROTEM. The present study suggested that DBCM, a novel method for measuring blood clotting, could provide the detail assessment for the status of anticoagulant therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum.

PubMed

Meissner, Mark H; Gloviczki, Peter; Comerota, Anthony J; Dalsing, Michael C; Eklof, Bo G; Gillespie, David L; Lohr, Joann M; McLafferty, Robert B; Murad, M Hassan; Padberg, Frank; Pappas, Peter; Raffetto, Joseph D; Wakefield, Thomas W

2012-05-01

The anticoagulant treatment of acute deep venous thrombosis (DVT) has been historically directed toward the prevention of recurrent venous thromboembolism. However, such treatment imperfectly protects against late manifestations of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, early thrombus removal strategies can potentially decrease postthrombotic morbidity. A committee of experts in venous disease was charged by the Society for Vascular Surgery and the American Venous Forum to develop evidence-based practice guidelines for early thrombus removal strategies, including catheter-directed pharmacologic thrombolysis, pharmacomechanical thrombolysis, and surgical thrombectomy. Evidence-based recommendations are based on a systematic review and meta-analysis of the relevant literature, supplemented when necessary by less rigorous data. Recommendations are made according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, incorporating the strength of the recommendation (strong: 1; weak: 2) and an evaluation of the level of the evidence (A to C). On the basis of the best evidence currently available, we recommend against routine use of the term "proximal venous thrombosis" in favor of more precise characterization of thrombi as involving the iliofemoral or femoropopliteal venous segments (Grade 1A). We further suggest the use of early thrombus removal strategies in ambulatory patients with good functional capacity and a first episode of iliofemoral DVT of <14 days in duration (Grade 2C) and strongly recommend their use in patients with limb-threatening ischemia due to iliofemoral venous outflow obstruction (Grade 1A). We suggest pharmacomechanical strategies over catheter-directed pharmacologic thrombolysis alone if resources are available and that surgical thrombectomy be considered if thrombolytic therapy is contraindicated (Grade 2C). Most data regarding early thrombus removal strategies are of low quality but do suggest patient-important benefits with respect to reducing postthrombotic morbidity. We anticipate revision of these guidelines as additional evidence becomes available. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Comparative study of Factor Xa fluorogenic substrates and their influence on the quantification of LMWHs.

PubMed

Castro-López, Vanessa; Harris, Leanne F; O'Donnell, James S; Killard, Anthony J

2011-01-01

Low molecular weight heparins (LMWHs) are recognised as the preferred anticoagulants in the prevention and treatment of venous thromboembolism. Anti-Factor Xa (anti-FXa) levels are used to monitor the anticoagulant effect of LMWHs and such assays are routinely employed in hospital diagnostic laboratories. In this study, a fluorogenic anti-FXa assay was developed using a commercially available fluorogenic substrate with an attached 6-amino-1-naphthalene-sulfonamide (ANSN) fluorophore and was used for the determination of two LMWHs, enoxaparin and tinzaparin and the heparinoid, danaparoid. The assay was based on the complexation of heparinised plasma with 100 nM exogenous FXa and 25 μM of the fluorogenic substrate Mes-D-LGR-ANSN (C(2)H(5))(2) (SN-7). The assay was tested with pooled plasma samples spiked with anticoagulant concentrations in the range 0-1.6 U mL(-1). The statistically sensitive assay range was 0-0.4 U mL(-1) for enoxaparin and tinzaparin and 0-0.2 U mL(-1) for danaparoid, with assay variation typically below 10.5%. This assay was then compared with a previously published fluorogenic anti-FXa assay developed with the peptide substrate, methylsulfonyl-D: -cyclohexylalanyl-glycyl-arginine-7-amino-4-methylcoumarin acetate (Pefafluor FXa). Both assays were compared in terms of fluorescence intensity, lag times and sensitivity to anticoagulants.

Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

PubMed

Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

2016-03-01

To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients. © 2015 American Heart Association, Inc.

Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin.

PubMed

Davidson, Bruce L; Verheijen, Sara; Lensing, Anthonie W A; Gebel, Martin; Brighton, Timothy A; Lyons, Roger M; Rehm, Jeffrey; Prins, Martin H

2014-06-01

Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented. To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism. Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009. Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure. Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios. During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens. Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.

Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

PubMed

Grosset-Janin, D; Barth, E; Bertrand, B; Detante, O

2015-05-01

Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral anticoagulation. Because of frequency of both atrial fibrillation and contraindication for oral anticoagulation, occlusion of the left atrial appendage should become an interesting alternative for many patients. However, it remains an invasive procedure and efficacy and indications need to be evaluated in further clinical trials. Risk/benefit ratio must be carefully assessed and compared to that of the new anticoagulant drugs. Copyright © 2015. Published by Elsevier Masson SAS.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

PubMed

Katada, Y; Nakagawa, S; Minakata, K; Odaka, M; Taue, H; Sato, Y; Yonezawa, A; Kayano, Y; Yano, I; Nakatsu, T; Sakamoto, K; Uehara, K; Sakaguchi, H; Yamazaki, K; Minatoya, K; Sakata, R; Matsubara, K

2017-10-01

Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, P<.005). The average time to reach the steady state was significantly (P<.005) shorter in the PBPM group compared to the control group (7.3 vs 8.6 days). Warfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kinnunen, Pete T T; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi

2017-08-29

Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

PubMed Central

Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

2017-01-01

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

PubMed

LaBonte, Michelle L

2014-09-01

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

[Physicians' Opinion on Health Care in Oral Anticoagulation].

PubMed

Eggebrecht, Lisa; Prochaska, Jürgen H; Schleuter, Leonie; Nagler, Markus; Hardt, Roland; Schinzel, Helmut; Münzel, Thomas; Wild, Philipp S

2018-05-01

 The introduction of direct oral anticoagulants (DOAC) in addition to the established Vitamin K antagonist (VKA) has increased the complexity of antithrombotic therapy leading to numerous treatment options. Studies of the medical evaluation of the current treatment situation by health care providers, which are of great importance for the development of treatment strategies in addition to studies on pharmacovigilance, are limited in the literature.  11 700 physicians (Rhineland-Palatinate, Germany) were contacted to participate in the web-based survey on health care with oral anticoagulation (OAC). After detailed quality control, the study was analysed in synopsis with routine care data of VKA patients of the thrombEVAL study programme (N = 2.011).  In total, 512 physicians (mean age: 48.0 ± 9.6 years; 74.0 % male) participated in the study. In general, quality of OAC therapy was rated as "average/satisfactory" (2.9 ± 0.9). Comparison of physicians' perception with data from routine care highlighted marked differences regarding time in therapeutic range (+ 6.4 % [95 %-CI 2.7 %; 9.5 %]), duration of control intervals (- 35.0 % [28.0 %; 41.4 %]) and rate of OAC-related complications (+ 61.8 [37.8 %; 83.3 %], which differed additionally and statistically-significant between physician groups. The willingness to use DOAC was approximately 50 % lower in general physicians as compared to specialists (36.6 % [25.4 %; 47.8 %] vs. 72.4 % [66.0 %; 78.9 %]; p < 0.0001). Regarding management of OAC therapy, 73.8 % [69.7 %; 77.9 %] advocated the establishment of a service hotline and 67.3 % [62,9 %; 71.6 %] a specialized coagulation service.  The present survey among physicians reveals a need for optimization of OAC therapy in daily practice. Specialized care models might facilitate optimized OAC therapy with both VKAs and DOACs. © Georg Thieme Verlag KG Stuttgart · New York.

Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.

PubMed

Bliden, Kevin P; Chaudhary, Rahul; Mohammed, Nafees; Muresan, Adina A; Lopez-Espina, Carlos G; Cohen, Eli; Raviv, Gabriel; Doubleday, Marc; Zaman, Fowzia; Mathew, Blessy; Tantry, Udaya S; Gurbel, Paul A

2017-05-01

Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.

Ischemic Stroke Risk in Patients With Atrial Fibrillation and CHA2DS2-VASc Score of 1: Systematic Review and Meta-Analysis.

PubMed

Joundi, Raed A; Cipriano, Lauren E; Sposato, Luciano A; Saposnik, Gustavo

2016-05-01

The CHA2DS2-VASc score aims to improve risk stratification of ischemic stroke among patients with atrial fibrillation to identify those who can safely forego oral anticoagulation. Oral anticoagulation treatment guidelines remain uncertain for CHA2DS2-VASc score of 1. We conducted a systematic review and meta-analysis of the risk of ischemic stroke for patients with atrial fibrillation and CHA2DS2-VASc score of 0, 1, or 2 not treated with oral anticoagulation. We searched MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from the start of the database up until April 15, 2015. We included studies that stratified the risk of ischemic stroke by CHA2DS2-VASc score for patients with nonvalvular atrial fibrillation. We estimated the summary annual rate of ischemic stroke using random effects meta-analyses and compared the estimated stroke rates with published net-benefit thresholds for initiating anticoagulants. 1162 abstracts were retrieved, of which 10 met all inclusion criteria for the study. There was substantial heterogeneity among studies. The summary estimate for the annual risk of ischemic stroke was 1.61% (95% confidence interval 0%-3.23%) for CHA2DS2-VASc score of 1, meeting the theoretical threshold for using novel oral anticoagulants (0.9%), but below the threshold for warfarin (1.7%). The summary incident risk of ischemic stroke was 0.68% (95% confidence interval 0.12%-1.23%) for CHA2DS2-VASc score of 0 and 2.49% (95% confidence interval 1.16%-3.83%) for CHA2DS2-VASc score of 2. Our meta-analysis of ischemic stroke risk in atrial fibrillation patients suggests that those with CHA2DS2-VASc score of 1 may be considered for a novel oral anticoagulant, but because of high heterogeneity, the decision should be based on individual patient characteristics. © 2016 American Heart Association, Inc.

Antithrombotic therapy in atrial fibrillation associated with valvular heart disease: a joint consensus document from the European Heart Rhythm Association (EHRA) and European Society of Cardiology Working Group on Thrombosis, endorsed by the ESC Working Group on Valvular Heart Disease, Cardiac Arrhythmia Society of Southern Africa (CASSA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

PubMed

Lip, Gregory Y H; Collet, Jean Philippe; Caterina, Raffaele de; Fauchier, Laurent; Lane, Deirdre A; Larsen, Torben B; Marin, Francisco; Morais, Joao; Narasimhan, Calambur; Olshansky, Brian; Pierard, Luc; Potpara, Tatjana; Sarrafzadegan, Nizal; Sliwa, Karen; Varela, Gonzalo; Vilahur, Gemma; Weiss, Thomas; Boriani, Giuseppe; Rocca, Bianca

2017-11-01

Atrial fibrillation (AF) is a major worldwide public health problem, and AF in association with valvular heart disease (VHD) is also common. However, management strategies for this group of patients have been less informed by randomized trials, which have largely focused on 'non-valvular AF' patients. Thrombo-embolic risk also varies according to valve lesion and may also be associated with CHA2DS2VASc score risk factor components, rather than only the valve disease being causal. Given marked heterogeneity in the definition of valvular and non-valvular AF and variable management strategies, including non-vitamin K antagonist oral anticoagulants (NOACs) in patients with VHD other than prosthetic heart valves or haemodynamically significant mitral valve disease, there is a need to provide expert recommendations for professionals participating in the care of patients presenting with AF and associated VHD. To address this topic, a Task Force was convened by the European Heart Rhythm Association (EHRA) and European Society of Cardiology (ESC) Working Group on Thrombosis, with representation from the ESC Working Group on Valvular Heart Disease, Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), South African Heart (SA Heart) Association and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE) with the remit to comprehensively review the published evidence, and to publish a joint consensus document on the management of patients with AF and associated VHD, with up-to-date consensus recommendations for clinical practice for different forms of VHD. This consensus document proposes that the term 'valvular AF' is outdated and given that any definition ultimately relates to the evaluated practical use of oral anticoagulation (OAC) type, we propose a functional Evaluated Heartvalves, Rheumatic or Artificial (EHRA) categorization in relation to the type of OAC use in patients with AF, as follows: (i) EHRA Type 1 VHD, which refers to AF patients with 'VHD needing therapy with a Vitamin K antagonist (VKA); and (ii) EHRA Type 2 VHD, which refers to AF patients with 'VHD needing therapy with a VKA or a Non-VKA oral anticoagulant (NOAC)', also taking into consideration CHA2DS2VASc score risk factor components. This consensus document also summarizes current developments in the field, and provides general recommendations for the management of these patients based on the principles of evidence-based medicine. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Venous thromboembolism: role of pharmacists and managed care considerations.

PubMed

Horner, Tuesdy; Mahan, Charles E

2017-12-01

Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Anticoagulation is used in patients with VTE to reduce the risk of recurrent VTE and VTE-related death. The overall incidence of VTE is 1 to 2 per 1000 person-years. Long-term mortality for patients with VTE is poor, with 25% of patients not surviving 7 days and nearly 40% not surviving the first year. Coagulation disorders demand effective anticoagulant therapy to avoid complications, especially recurrent VTE and VTE-related death. For more than 60 years, warfarin has been the cornerstone of therapy for patients requiring anticoagulation and was the sole oral anticoagulant available in the United States until 2010. Since then, the FDA has approved 5 direct-acting oral anticoagulants (DOACs) that inhibit single coagulation factors (factor Xa and thrombin). DOACs provide predictable anticoagulation with fixed dosing, easier perioperative management, no routine laboratory monitoring, and fewer food-drug interactions. However, when choosing DOACs, clinicians must consider several issues in addition to efficacy and safety before employing these therapies, including patient-specific factors, adherence and persistence with therapy, and their cost-effectiveness for clinical use.

Antioxidant and anticoagulant activity of polyphenol and polysaccharides from fermented Sargassum sp.

PubMed

Shobharani, P; Nanishankar, V H; Halami, P M; Sachindra, N M

2014-04-01

The current investigation was carried out with an objective of determining the structural characteristic of polysaccharides extracted from fermented Sargassum sp. to be used as potent natural heparin substitute anticoagulant compound. Sargassum sp. fermented with marine lactic acid bacteria was initially subjected to ethanol precipitation for the recovery of bioactive compounds. Antioxidant activity was maximum in the soluble fraction whereas anticoagulant activity was observed to be high in the precipitate which correlated with the increased polyphenols and total sugars respectively. The precipitate was purified by anion exchange chromatography and the fractions collected were analyzed for total sugars and anticoagulant activity. There was 2.6-3.9-folds increase in anticoagulant activity in the final purified fractions, with a maximum activity in case of sample fermented with Enterococcus faecium (6.7±0.22 IU/mg). Structural elucidation of potential anticoagulant polysaccharide by Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) analysis indicated the presence of alginate rich in mannuronic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

PubMed

del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

2015-10-01

New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Anticoagulant management in the cardiovascular setting.

PubMed

Verheugt, Freek W A

2012-02-01

Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under-anticoagulation (i.e. thrombosis formation) or over-anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few drug-drug interactions and do not require routine coagulation monitoring. © 2011 The Author Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Acute major gastrointestinal bleeding caused by hookworm infection in a patient on warfarin therapy: A case report.

PubMed

Meng, Yu; Lu, FangGen; Shi, Lin; Cheng, MeiChu; Zhang, Jie

2018-03-01

The use of anticoagulants is a contributor to gastrointestinal (GI) bleeding. Most bleeding patients on anticoagulant therapy such as warfarin commonly have basic lesions existing in their GI mucosa. We report a case of major GI bleeding following the use of anticoagulants in a patient with hookworm infection. The patient was diagnosed with nephrotic syndrome with pulmonary embolism. He was treated with anticoagulants and suffered from acute major GI bleeding during the treatment. Capsule endoscopy revealed many hookworms in the lumen of jejunum where fresh blood was seen coming from the mucosa. The patient was successfully rescued and cured with albendazole. Latent hookworm infection can be a cause of massive small-bowel hemorrhage in patients on anticoagulant therapy and anthelmintic treatment is the key to stop bleeding.

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation.

PubMed

Norby, Faye L; Bengtson, Lindsay G S; Lutsey, Pamela L; Chen, Lin Y; MacLehose, Richard F; Chamberlain, Alanna M; Rapson, Ian; Alonso, Alvaro

2017-09-06

Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Changes in hemolymph characteristics of ark shell Scapharaca broughtonii dealt with Vibrio anguillarum challenge in vivo and various of anticoagulants in vitro.

PubMed

Zhou, Liqing; Yang, Aiguo; Liu, Zhihong; Wu, Biao; Sun, Xiujun; Lv, Zhenming; Tian, Ji-Teng; Du, Meirong

2017-02-01

The ark shell Scapharca broughtonii is a commercially important shellfish in China. Alserver's solution (AS), modified Alserver's solution (MAS) and Heparin sodium solution (HSS) are common anticoagulants used for shellfish blood. To observe the immune response mediated by its hemocytes, we challenged in vivo S. broughtonii hemolymph with Vibrio anguillarum and dealt with the following three anticoagulants in vitro: Alserver's solution (AS), modified Alserver's solution (MAS) and Heparin sodium solution (HSS). The methodologies we used were immunostimulation with V. anguillarum, Wright-Giemsa staining, micro-examination, and flow cytometric and hydrolyzing enzyme activity analysis. The results showed that all three types of anticoagulants effectively prevented blood clotting in ark shellfish. The morphology of hemocytes did not significantly change 30 h after anticoagulant treatment, except for the shrinking of hemocytes after administering HSS. The size and permeability of hemocytes changed when treated with the anticoagulants and when stimulated with V. anguillarum. Both alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemocytes and Plasma were measured at different times after they were stimulated with V. anguillarum in HSS and MAS. The AKP enzymatic activity in HSS was somewhat higher than in the MAS anticoagulant, but changes in response to V. anguillarum challenge of enzymatic activity were almost the same in HSS and MAS groups. In conclusion, all three types of anticoagulants may be used for ark shell blood preservation. They all changed the cell-surface characteristics of hemocytes to inhibit clot formation. The AS anticoagulant was appropriate for maintaining white and red cell shapes, while MAS was ideal for retaining throbus cell function. Lastly, HSS was appropriate for maintaining enzymatic activity in hemolymph and function of hemocytes. Following this investigation, we gained insight into the changes in hemolymph characteristic during immune response. Copyright © 2016. Published by Elsevier Ltd.

Future Research Opportunities in Peri-Prosthetic Joint Infection Prevention.

PubMed

Berbari, Elie; Segreti, John; Parvizi, Javad; Berríos-Torres, Sandra I

Peri-prosthetic joint infection (PJI) is a serious complication of prosthetic joint arthroplasty. A better understanding and reversal of modifiable risk factors may lead to a reduction in the incidence of incisional (superficial and deep) and organ/space (e.g., PJI) surgical site infections (SSI). Recently, the Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC) published the Guideline for Prevention of Surgical Site Infection. This targeted update applies evidence-based methodology in drafting recommendations for potential strategies to reduce the risk of SSI both across surgical procedures and specifically in prosthetic joint arthroplasty. A panel of PJI content experts identified nine PJI prevention research opportunities based on both evidence gaps identified through the guideline development process (transfusion, immunosuppressive therapy, anticoagulation, orthopedic space suit, and biofilm) and expert opinion (anesthesia, operative room environment, glycemic control, and Staphylococcus aureus nasal screening and decolonization. This article offers a road map for PJI prevention research.

Impact of a Focused Approach for Discharge Teaching Regarding the Use of Aspirin as Anticoagulant After Joint Replacement Surgery.

PubMed

Wittig-Wells, Deborah; Higgins, Melinda; Davis, Erica; Johnson, Ifeya; Louis, Latalya; Mason, Olga; Samms-McPherson, Jacqueline; Sims, Sandra; Jacob, Ani

2015-01-01

Patient education for the use and administration of aspirin (ASA) as an anticoagulant may be deficient. To pilot a knowledge assessment tool regarding the use of aspirin (ASA) as an anticoagulant and to evaluate the impact of a focused approach for discharge teaching. One-group pretest-posttest pilot study. Convenience sample of patients hospitalized for total knee and total hip arthroplasty. Researcher developed ASA quiz. Focused education on aspirin as an anticoagulant. There was a statistically significant improvement in knowledge (Wilcoxon rank sum test Z = 3.880, p < .001).

[New oral anticoagulant drugs].

PubMed

Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

2011-10-01

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

Disadvantages of VKA and requirements for novel anticoagulants.

PubMed

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Bivalirudin for Pediatric Procedural Anticoagulation: A Narrative Review.

PubMed

Zaleski, Katherine L; DiNardo, James A; Nasr, Viviane G

2018-02-14

Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ), a direct thrombin inhibitor, has found increasing utilization as a heparin alternative in the pediatric population, most commonly for the treatment of thrombosis secondary to heparin-induced thrombocytopenia. Due to the relative rarity of heparin-induced thrombocytopenia as well as the lack of Food and Drug Administration-approved indications in this age group, much of what is known regarding the pharmacokinetics and pharmacodynamics of bivalirudin in this population has been extrapolated from adult data. This narrative review will present recommendations regarding the use of bivalirudin for procedural anticoagulation in the pediatric population based on the published literature.

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

PubMed

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Clinical and economic benefits of extended treatment with apixaban for the treatment and prevention of recurrent venous thromboembolism in Canada.

PubMed

Quon, Peter; Le, Hoa H; Raymond, Vincent; Mtibaa, Mondher; Moshyk, Andriy

2016-06-01

Background and objective Venous thromboembolism (VTE) is associated with long-term clinical and economic burden. Clinical guidelines generally recommend at least 3 months of anticoagulation, but, in clinical practice, concerns over bleeding risk often limit extended treatment. Apixaban was studied for extended VTE treatment in the AMPLIFY-EXT trial, demonstrating superiority to placebo in VTE reduction without increasing risk of major bleeding. This study assessed the long-term clinical and economic benefits of extending treatment with apixaban when clinical equipoise exists compared to standard of care with enoxaparin/warfarin and other novel oral anti-coagulants (NOACs) for the treatment and prevention of recurrent VTE in Canada. Methods A Markov model was developed to follow patients with VTE over their lifetimes. Efficacy and safety for apixaban and enoxaparin/warfarin were based on AMPLIFY and AMPLIFY-EXT, while relative efficacy to other NOACs was synthesized by network meta-analysis (NMA). Dosages for NOACs and enoxaparin/warfarin were based on their respective trials and were given up to 18 months and up to 6 months, followed by no treatment, respectively. Patient quality adjusted life years (QALYs) were based on published studies, and costs for resource utilization were from a Ministry of Health perspective, expressed as 2014 CAD ($). Results Extended treatment with apixaban compared to enoxaparin/warfarin resulted in fewer recurrent VTEs, VTE-related deaths, and bleeding events, but at slightly increased cost. The incremental cost-effectiveness ratio was $4828 per QALY gained. Compared to other NOACs, apixaban had the fewest bleeding events, similar recurrent VTE events, and the lowest overall cost, which was driven by the strong bleeding profile. In scenario analyses of acute and lifetime treatments, apixaban was cost-effective against all strategies. Conclusions Extended treatment with apixaban can offer substantial clinical benefits and is a cost-effective alternative to enoxaparin/warfarin and other NOACs.

Anticoagulation Therapy for Venous Thromboembolism in the Real World　- From the COMMAND VTE Registry.

PubMed

Yamashita, Yugo; Morimoto, Takeshi; Amano, Hidewo; Takase, Toru; Hiramori, Seiichi; Kim, Kitae; Konishi, Takashi; Akao, Masaharu; Kobayashi, Yohei; Inoue, Takeshi; Oi, Maki; Izumi, Toshiaki; Takahashi, Kotaro; Tada, Tomohisa; Chen, Po-Min; Murata, Koichiro; Tsuyuki, Yoshiaki; Sakai, Hiroshi; Saga, Syunsuke; Sasa, Tomoki; Sakamoto, Jiro; Yamada, Chinatsu; Kinoshita, Minako; Togi, Kiyonori; Ikeda, Tomoyuki; Ishii, Katsuhisa; Kaneda, Kazuhisa; Mabuchi, Hiroshi; Otani, Hideo; Takabayashi, Kensuke; Takahashi, Mamoru; Shiomi, Hiroki; Makiyama, Takeru; Ono, Koh; Kimura, Takeshi

2018-04-25

Venous thromboembolism (VTE) has a long-term risk of recurrence, which can be prevented by anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE between January 2010 and August 2014. The entire cohort was divided into the transient risk (n=855, 28%), unprovoked (n=1,477, 49%), and cancer groups (n=695, 23%). The rate of anticoagulation discontinuation was highest in the cancer group (transient risk: 37.3% vs. unprovoked: 21.4% vs. cancer: 43.5% at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding and all-cause death were highest in the cancer group (recurrent VTE: 7.9% vs. 9.3% vs. 17.7%, P<0.001; major bleeding: 9.0% vs. 9.4% vs. 26.6%, P<0.001; and all-cause death: 17.4% vs. 15.3% vs. 73.1%, P<0.001). After discontinuation of anticoagulation therapy, the cumulative 3-year incidence of recurrent VTE was lowest in the transient risk group (transient risk: 6.1% vs. unprovoked: 15.3% vs. cancer: 13.2%, P=0.001). The cumulative 3-year incidence of recurrent VTE beyond 1 year was lower in patients on anticoagulation than in patients off anticoagulation at 1 year in the unprovoked group (on: 3.7% vs. off: 12.2%, P<0.001), but not in the transient risk and cancer groups (respectively, 1.6% vs. 2.5%, P=0.30; 5.6% vs. 8.6%, P=0.44). The duration of anticoagulation therapy varied widely in discordance with current guideline recommendations. Optimal duration of anticoagulation therapy should be defined according to the risk of recurrent VTE and bleeding as well as death.

Rapid bedside coagulometry prior to urgent neurosurgical procedures in anticoagulated patients.

PubMed

Beynon, Christopher; Jakobs, Martin; Rizos, Timolaos; Unterberg, Andreas W; Sakowitz, Oliver W

2014-01-01

With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. The POC coagulometer CoaguChek XS(®) was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37-61 min). Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

PubMed

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses

PubMed Central

Protasiewicz, Marcin; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research. PMID:24570697

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses.

PubMed

Protasiewicz, Marcin; Rojek, Aleksandra; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; de Labriolle, Axel; Haguenoer, Ken; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

2010-04-01

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.

Progressively Worsening Premature Coronary Artery Disease: Adding Anticoagulation Stabilizes-Reverses Clinical Symptomatic Disease Progression in Thrombophilic-Atherothrombotic Patients: A Pilot Study.

PubMed

Rothschild, Matan; Jetty, Vybhav; Mahida, Christopher; Wang, Ping; Prince, Marloe; Goldenberg, Naila; Glueck, Charles J

2017-11-01

In 35 patients with 116 severe premature cardiovascular disease (CVD) events (median age: 48 years), 14 having worsening CVD despite maximal intervention, we evaluated thrombophilia and speculated that anticoagulation might arrest-reverse progressive thrombophilic-atherothrombotic CVD. Thrombophilia-hypofibrinolysis in the 35 patients was compared to 110 patients with venous thromboembolism (VTE) without CVD and to 110 healthy normal controls. Efficacy-safety of anticoagulation was prospectively assessed in 14 of the 35 patients whose CVD worsened over 2 years despite maximal medical-surgical intervention. At entry on maximally tolerated lipid-lowering therapy, median low-density lipoprotein was 88 mg/dL. Measures of thrombophilia-hypofibrinolysis in the 35 cases differed from 110 VTE controls only for the lupus anticoagulant, present in 6 (21%) of 28 cases versus 4 (4%) of 91 VTE controls ( P = .01), and for high anticardiolipin antibodies (ACLAs) immunoglobulin G, 5 (14%) of 35 cases versus 4 of 108 VTE controls (4%), P = .04. The 14 patients who were anticoagulated differed from 110 VTE controls only for the lupus anticoagulant, 38% versus 4%, P = .001, and for high lipoprotein (a), 46% versus 17%, P = .028, respectively. The 14 patients with atherothrombosis having inexorably worsening CAD despite maximal medical-surgical therapy were anticoagulated for 6.5 years (median), with clinical CVD progression arrested in 12 (86%), and all 12 became asymptomatic. In the 35 patients with premature CVD, thrombophilia was pervasive, comparable to or more severe than in VTE controls without CVD. When CVD progressively worsens despite maximal intervention, thrombophilia and atherosclerosis (atherothrombosis) are commonly concurrent, and the downhill course of CVD may be arrested-stabilized by anticoagulation.

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

PubMed

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent or urgent surgery or in patients with severe bleeding.

Transportation cost of anticoagulation clinic visits in an urban setting.

PubMed

Hwang, Jamie M; Clemente, Jennifer; Sharma, Krishna P; Taylor, Thomas N; Garwood, Candice L

2011-10-01

Patients being managed on warfarin make frequent or regular visits to anticoagulation monitoring appointments. International studies have evaluated transportation cost and associated time related to anticoagulation clinic visits. To our knowledge, no studies have evaluated the cost of transportation to such clinic visits in the United States. To describe the methods of transportation and estimate the average total cost of transportation to and from an anticoagulation clinic in an urban setting. We prospectively conducted a survey of patients treated at the Harper Anticoagulation Clinic located in Detroit, Michigan, during November 2010. The survey was given to patients while waiting at their regularly scheduled clinic appointments and included questions regarding mode of transportation, distance traveled in miles, parking payment, and time missed from work for clinic appointments. The mean distance traveled was translated into cost assuming 50 cents per mile based on 2010 estimates by the Internal Revenue Service. Sixty patients responded to the 11-item survey; response rates for individual items varied because participants were instructed to skip questions that did not pertain to them. Of the 47 participants responding to demographic questions, 70.2% were female, and 46.8% were older than 60 years. Transportation by private vehicle (80.0%), either driven by patients (41.7%) or someone else (38.3%), was the most common method reported. Use of private automobile translated into a cost of $11.19 per round trip. Other means of transportation identified include a ride from a medical transportation service (10.0%), bus (5.0%), walking (3.3%), and taxi (1.7%). The mean (SD) distance traveled to the clinic for all methods of transportation was 8.34 (7.7) miles. We estimated the average cost of round-trip transportation to be $10.78 weighted for all transportation modes. This is a direct nonmedical cost that is paid for by most patients out of pocket. However, 9 of 44 (20.5%) responded that their insurance plans provided at least some coverage for their rides to the anticoagulation clinic. Most participants stated that they did not take any time off work for clinic visits (88%) primarily because a large proportion of the study population was unemployed or retired. The round-trip cost of transportation to an anticoagulation clinic in an urban setting in the United States may translate into a substantial expense, ranging from weekly appointments ($560 annually) to once monthly appointments ($130 annually).

Thrombophilia and Recurrent Pregnancy Loss

PubMed Central

Abu-Heija, Adel

2014-01-01

The association between thrombophilia and recurrent pregnancy loss (RPL) has become an undisputed fact. Thorombophilia creates a hypercoaguable state which leads to arterial and/or venous thrombosis at the site of implantation or in the placental blood vessels. Anticoagulants are an effective treatment against RPL in women with acquired thrombophilia due to antiphospholipid syndrome. The results of the use of anticoagulants for treating RPL in women with inherited thrombophilia (IT) are encouraging, but recently four major multicentre studies have shown that fetal outcomes (determined by live birth rates) may not be as favourable as previously suggested. Although the reported side-effects for anticoagulants are rare and usually reversible, the current recommendation is not to use anticoagulants in women with RPL and IT, or for those with unexplained losses. This review examines the strength of the association between thrombophilia and RPL and whether the use of anticoagulants can improve fetal outcomes. PMID:24516750

Decision-making interventions to stop the global atrial fibrillation-related stroke tsunami.

PubMed

Cerasuolo, Joshua O; Montero-Odasso, Manuel; Ibañez, Agustin; Doocy, Shannon; Lip, Gregory Yh; Sposato, Luciano A

2017-04-01

Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

Conservative management of neonatal cerebral sinovenous thrombosis with coexisting thrombophilia.

PubMed

Khatri, Vidushi; Chan, Anthony K C; Stein, Nina; Paes, Bosco; Bhatt, Mihir

2018-06-01

: Neonatal cerebral sinovenous thrombosis (CSVT) comprises approximately 50% of all pediatric-related CSVT. Although guidelines support anticoagulation in pediatric CSVT, the role of anticoagulation in neonatal CSVT remains controversial. This case report details the course of a neonate diagnosed with extensive CSVT and concurrent bilateral thalamic and intraventricular hemorrhage. Due to existing hemorrhage at the time of diagnosis, anticoagulation therapy was not administered. Despite coexisting protein C and antithrombin deficiency, CSVT resolved spontaneously, and neurodevelopmental follow-up after 13 years suggests a good prognosis. Although our case had a positive outcome, the association between the use of anticoagulation with concurrent hemorrhage and long-term outcome in neonatal CSVT has not been investigated in prospective studies to firmly guide optimum treatment. Current literature and guidelines for the treatment of neonatal CSVT are reviewed in this article. Until robust studies are available, expert opinion recommends anticoagulation in a stable neonate with CSVT.

Mild brain injury and anticoagulants: Less is enough.

PubMed

Campiglio, Laura; Bianchi, Francesca; Cattalini, Claudio; Belvedere, Daniela; Rosci, Chiara Emilia; Casellato, Chiara Livia; Secchi, Manuela; Saetti, Maria Cristina; Baratelli, Elena; Innocenti, Alessandro; Cova, Ilaria; Gambini, Chiara; Romano, Luca; Oggioni, Gaia; Pagani, Rossella; Gardinali, Marco; Priori, Alberto

2017-08-01

Despite the higher theoretical risk of traumatic intracranial hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of sequential head CT scans to identify bleeding remains controversial. This study evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral anticoagulants. We retrospectively evaluated the clinical records of all patients on chronic anticoagulation treatment admitted to the emergency department for mild head injury. A total of 344 patients were included, and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients with a negative CT1 and was positive in 4 patients (1.4%), but none of the patients developed concomitant neurologic worsening or required neurosurgery. Systematic routine use of a second CT scan in mild head trauma in patients taking anticoagulants is expensive and clinically unnecessary.

Diagnosis and management of factor V Leiden.

PubMed

Campello, Elena; Spiezia, Luca; Simioni, Paolo

2016-12-01

The discovery of the factor V Leiden (FVL) missense mutation (Arg506Gln) causing factor V resistance to the anticoagulant action of activated protein C was a landmark that allowed a better understanding of the basis of inherited thrombotic risk. FVL mutation is currently the most common known hereditary defect predisposing to venous thrombosis. Areas covered: Novel data-driven FVL diagnosis and therapeutic approaches in the management of FVL carriers in various clinical settings. Brief conclusions on topics of direct clinical relevance including currently available indications for primary and secondary prophylaxis, the management of female, pediatric carriers and asymptomatic relatives. Latest evidence on the association between FVL and cancer, as well as the possible use of direct oral anticoagulant therapy. Expert commentary: Although FVL diagnosis nowadays is highly accurate, many doubts remain regarding the best management and therapeutic protocols. The main role of clinicians is to tailor therapeutic strategies to carriers and their relatives. High familial penetrance, distinctive aspects of the first thrombotic event (provoked/unprovoked, age, etc.) and laboratory biomarkers can guide the optimal management of secondary antithrombotic prophylaxis, primary prophylaxis in asymptomatic individuals, and whether to screen relatives.

Catastrophic antiphospholipid syndrome: a clinical review.

PubMed

Nayer, Ali; Ortega, Luis M

2014-01-01

Catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening autoimmune disease characterized by disseminated intravascular thrombosis resulting in multiorgan failure. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. CAPS is due to antiphospholipid antibodies directed against a heterogeneous group of proteins that are associated with phospholipids. These autoantibodies activate endothelial cells, platelets, and immune cells, thereby promoting a proinflammatory and prothrombotic phenotype. Furthermore, antiphospholipid antibodies inhibit anticoagulants, impair fibrinolysis, and activate complements. Although CAPS can affect a variety of organs and tissues, the kidneys, lungs, central nervous system, heart, skin, liver, and gastrointestinal tract are most commonly affected. The systemic inflammatory response syndrome, likely to extensive tissue damage, accompanies CAPS. The most frequent renal manifestations are hypertension, proteinuria, hematuria, and acute renal failure.In the majority of patients with CAPS, a precipitating factor such as infection, surgery, or medication can be identified. Antiphospholipid antibodies such as lupus anticoagulant and antibodies against cardiolipin, β2-glycoprotein I, and prothrombin are serological hallmark of CAPS. Laboratory tests often reveal antinuclear antibodies, thrombocytopenia, and anemia. Despite widespread intravascular coagulation, blood films reveal only a small number of schistocytes. In addition, severe thrombocytopenia is uncommon. Histologically, CAPS is characterized by acute thrombotic microangiopathy. CAPS must be distinguished from other forms of thrombotic microangiopathies such as hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and heparin-induced thrombocyt openia. CAPS is associated with high morbidity and mortality. Therefore, an aggressive multidisciplinary treatment strategy is indicated. Anticoagulation, immunosuppression, plasma exchange, intravenous immunoglobulins, and anti-platelet agents, used in various combinations, have resulted in improved patient outcome.

Use of anticoagulant rodenticides by pest management professionals in Massachusetts, USA.

PubMed

Memmott, Kristin; Murray, Maureen; Rutberg, Allen

2017-01-01

Secondary exposure to chemical rodenticides, specifically second-generation anticoagulant rodenticides (SGARs), poses a threat to non-target wildlife including birds of prey. Federal regulations in the United States currently limit homeowner access to SGARs as a way of minimizing this threat. With legal access to SGARs, pest management professionals (PMPs) represent a potential linkage to non-target exposure. There is limited research focused on rodent control practices, chemical rodenticide preferences, level of concern and awareness, or opinions on rodenticide regulations as they relate to PMPs. An online survey was sent to PMP companies across Massachusetts, USA, between October and November 2015. Thirty-five responses were obtained, a 20 % response rate. The preferred rodent control method among responding PMP companies was chemical rodenticides, specifically the SGAR bromadiolone. Respondents varied in their level of concern regarding the impact of chemical rodenticides on non-target species and showed a low level of awareness regarding SGAR potency and half-life. All responding companies reported using integrated pest management (IPM) strategies, with nearly all utilizing chemical rodenticides at some point. Enhanced education focused on SGAR potency, bioaccumulation potential, exposure routes, and negative impacts on non-target wildlife may improve efforts made by PMPs to minimize risk to wildlife and decrease dependence on chemical rodenticide use. Future studies evaluating use of anticoagulant rodenticide (ARs) by PMPs and the association with AR residues found in non-target wildlife is necessary to determine if current EPA regulations need to be modified to effectively reduce the risk of SGARs to non-target wildlife.

Direct oral anticoagulants and digestive bleeding: therapeutic management and preventive measures.

PubMed

Deutsch, David; Boustière, Christian; Ferrari, Emile; Albaladejo, Pierre; Morange, Pierre-Emmanuel; Benamouzig, Robert

2017-06-01

The use of direct oral anticoagulants (DOACs) was an important step forward in the management of atrial fibrillation and venous thromboembolism (VTE). The DOACs, anti-IIa for dabigatran and anti-Xa for rivaroxaban, apixaban and edoxaban, all have a rapid onset of action and a short half life. There is no need for routine hemostasis testing for treatment monitoring of a DOAC. Compared with vitamin K antagonists (VKAs), DOACs may increase the risk of gastrointestinal bleeding (relative risk 1.25). Withholding the DOAC treatment, evaluating the time of the last intake and estimating the patient's renal function are the first steps in the management of gastrointestinal bleeding. For patients without impaired renal function, achieving low coagulation takes around 24 h after the last intake of a DOAC. The use of DOAC antagonists will be helpful in controlling bleeding in the most severe and urgent situations. Idarucizumab is available for clinical use for dabigatran and andexanet is currently being reviewed by drug agencies for rivaroxaban, apixaban and edoxaban. It is important to assess the bleeding risk associated with the planned procedure, and the patient's renal function before withholding DOAC therapy for a scheduled intervention. It is mandatory to strengthen the local hemostasis strategies in DOAC-treated patients undergoing a therapeutic endoscopic procedure. Resuming or not resuming anticoagulation with a DOAC after bleeding or a risky procedure depends on the thrombotic and bleeding risk as well as the procedure involved. This discussion should always involve the cardiologist and decisions should be taken by a pluridisciplinary team.

Mobile Health Technology for Atrial Fibrillation Management Integrating Decision Support, Education, and Patient Involvement: mAF App Trial.

PubMed

Guo, Yutao; Chen, Yundai; Lane, Deirdre A; Liu, Lihong; Wang, Yutang; Lip, Gregory Y H

2017-12-01

Mobile Health technology for the management of patients with atrial fibrillation is unknown. The simple mobile AF (mAF) App was designed to incorporate clinical decision-support tools (CHA 2 DS 2 -VASc [Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA, Vascular disease, Age 65-74 years, Sex category], HAS-BLED [Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly], SAMe-TT 2 R 2 [Sex, Age <60 years, Medical history, Treatment, Tobacco use, Race] scores), educational materials, and patient involvement strategies with self-care protocols and structured follow-up. Patients with atrial fibrillation were randomized into 2 groups (mAF App vs usual care) in a cluster randomized design pilot study. Patients' knowledge, quality of life, drug adherence, and anticoagulation satisfaction were evaluated at baseline, 1 month, and 3 months. Usability, feasibility, and acceptability of the mAF App were assessed at 1 month. A total of 113 patients were randomized to mAF App intervention (mean age, 67.4 years; 57.5% were male; mean follow-up, 69 days), and 96 patients were randomized to usual care (mean age, 70.9 years; 55.2% were male; mean follow-up, 95 days). More than 90% of patients reported that the mAF App was easy, user-friendly, helpful, and associated with significant improvements in knowledge compared with the usual care arm (P values for trend <.05). Drug adherence and anticoagulant satisfaction were significantly better with the mAF App versus usual care (all P < .05). Quality of life scores were significantly increased in the mAF App arm versus usual care, with anxiety and depression reduced (all P < .05). The pilot mAFA Trial is the first prospective randomized trial of Mobile Health technology in patients with atrial fibrillation, demonstrating that the mAF App, integrating clinical decision support, education, and patient-involvement strategies, significantly improved knowledge, drug adherence, quality of life, and anticoagulation satisfaction. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cardiac Tamponade Associated with Rivaroxaban.

PubMed

Boone, Stephen

2015-07-01

Rivaroxaban is an oral anticoagulant approved for prevention of stroke, as well as for the treatment and prevention of venous thromboembolic disease. Hemopericardium is a serious complication of anticoagulant use, which has been reported with oral vitamin-K antagonists and newer oral anticoagulants. At the time of this report, to my knowledge, there are no published reports of hemorrhagic effusion leading to tamponade associated with a Factor Xa Inhibitor. I report a case of hemopericardium with associated tamponade in a patient who developed pericarditis while being treated with Rivaroxaban. The case highlights an important adverse effect of a newer anticoagulant, as well as the particular dangers of medication co-administration in the elderly.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

PubMed Central

Fu, Zhong-Hua; Guo, Guang-Hua; Xiong, Zhen-Fang; Liao, Xincheng; Liu, Ming-Zhuo; Luo, Jinhua

2017-01-01

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury. PMID:28944866

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

PubMed

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

PubMed

Liu, Michelle Y; Ballard, Dustin W; Huang, Jie; Rauchwerger, Adina S; Reed, Mary E; Bouvet, Sean C; Vinson, David R

2018-05-01

Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III-V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0-3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation

PubMed Central

Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.

2018-01-01

Introduction Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. Methods From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Results Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III–V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0–3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. Conclusion We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence. PMID:29760849

Stroke prophylaxis in atrial fibrillation: searching for management improvement opportunities in the emergency department: the HERMES-AF study.

PubMed

Coll-Vinent, Blanca; Martín, Alfonso; Malagón, Francisco; Suero, Coral; Sánchez, Juan; Varona, Mercedes; Cancio, Manuel; Sánchez, Susana; Montull, Eugeni; Del Arco, Carmen

2015-01-01

We determine the prevalence of stroke prophylaxis prescription in emergency department (ED) patients with atrial fibrillation and the factors associated with a lack of prescription of anticoagulation in high-risk patients without contraindications. This was a multicenter, observational, cross-sectional study with prospective standardized data collection carried out in 124 Spanish EDs. Clinical variables, risk factors for stroke, type of prophylaxis prescribed, and reasons for not prescribing anticoagulation in high-risk patients (congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes and previous stroke/transient ischemic attack/systemic embolism [CHADS2] score ≥2 and the congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes, previous stroke/transient ischemic attack/systemic embolism, vascular disease age 65 to 74 years and sex category [CHA2DS2-VASc] score ≥2) without contraindications were collected. Of 3,276 patients enrolled, 71.5% were at high risk according to CHADS2; 89.7% according to CHA2DS2-VASc. At discharge from the ED, 2,255 patients (68.8%) were receiving anticoagulants, 1,691 of whom (75%) were high-risk patients. Of the 1,931 patients discharged home, anticoagulation was prescribed for 384 patients (19.9%) de novo and for 932 patients (48.3%) previously receiving anticoagulation. The main reasons for not prescribing anticoagulation to eligible patients were considering antiplatelet therapy as adequate prophylaxis (33.1%), advanced age (15%), and considering stroke risk as low (8.3%). Advanced age (odds ratio 0.46; 95% confidence interval 0.30 to 0.69) and female sex (odds ratio 0.50; 95% confidence interval 0.36 to 0.71) were significantly associated with the lack of prescription of anticoagulation to eligible patients. In Spain, most patients with atrial fibrillation treated in EDs who do not receive anticoagulation are at high risk of stroke, with relevant differences with regard to the risk stratification scheme used. Anticoagulation is underused, mainly because the risk of stroke is underestimated by the treating physicians and the benefits of antiplatelets are overrated, principally in female patients and the elderly. Efforts to increase the prescription of anticoagulation in these patients appear warranted. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2015-03-14

There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not significantly influence cell counts or GF concentrations in equine PRP. However, ACD-B was apparently the worst anticoagulant evaluated. It is necessary to perform additional research to determine the effect of anticoagulants on the kinetics of GF elution from P-PRG.

Rivaroxaban in the treatment of venous thromboembolism and the prevention of recurrences: a practical approach.

PubMed

Arcelus, Juan I; Domènech, Pere; Fernández-Capitan, Ma Del Carmen; Guijarro, Ricardo; Jiménez, David; Jiménez, Sonia; Lozano, Francisco S; Monreal, Manel; Nieto, José A; Páramo, José A

2015-05-01

Anticoagulation therapy is the standard treatment of patients with symptomatic venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism. Until recently, treatment of VTE was based on parenteral or low-molecular-weight heparin for initial therapy (5-10 days) and oral vitamin K antagonists for long-term therapy. Those treatments have some limitations, including parenteral administration (heparins), the need for frequent monitoring and dose adjustments, interactions with several medications, and dietary restrictions (vitamin K antagonists). Rivaroxaban is a new oral direct factor Xa inhibitor with a wide therapeutic window, predictable anticoagulant effect, no food interactions, and few drug interactions. Consequently, no periodic monitoring of anticoagulation is needed, and fixed doses can be prescribed. EINSTEIN program demonstrated that rivaroxaban was as effective as and significantly safer than standard therapy for treatment of VTE. Rivaroxaban was recently authorized so doubts exist about how to use it in daily clinical practice. This document aims to clarify common questions formulated by clinicians regarding the use of this new drug. © The Author(s) 2014.

Effect of oral anticoagulants on the outcome of faecal immunochemical test

PubMed Central

Bujanda, L; Sarasqueta, C; Lanas, Á; Quintero, E; Cubiella, J; Hernandez, V; Morillas, J D; Perez-Fernández, T; Salas, D; Andreu, M; Carballo, F; Bessa, X; Portillo, I; Jover, R; Balaguer, F; Cosme, A; Castells, A

2014-01-01

Background: We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening. Methods: Individuals aged 50–69 years were invited to receive one FIT sample (cutoff 75 ng ml–1) between November 2008 and June 2011. Results: Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3–1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4–10.8; P=0.4). Conclusions: Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets. PMID:24496455

Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

PubMed

Hammerstingl, C

2008-10-01

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

Evaluating the potential for pharmacists to prescribe oral anticoagulants for atrial fibrillation

PubMed Central

Sandhu, Roopinder K.; Guirguis, Lisa M.; Bungard, Tammy J.; Youngson, Erik; Brehaut, Jamie C.; Healey, Jeff S.; McAlister, Finlay A.

2017-01-01

Background: Oral anticoagulant therapy (OAC) to prevent atrial fibrillation (AF)–related strokes remains poorly used. Alternate strategies, such as community pharmacist prescribing of OAC, should be explored. Methods: Approximately 400 pharmacists, half with additional prescribing authority (APA), randomly selected from the Alberta College of Pharmacists, were invited to participate in an online survey over a 6-week period. The survey consisted of demographics, case scenarios assessing appropriateness of OAC (based on the 2014 Canadian Cardiovascular Society AF guidelines) and perceived barriers to prescribing. Regression analysis was performed to determine predictors of knowledge. Results: A total of 35% (139/397) of pharmacists responded to the survey, and 57% of these had APA. Depending on the case scenario, 55% to 92% of pharmacists correctly identified patients eligible for stroke prevention therapy, but only about a half selected the appropriate antithrombotic agent; there was no difference in the knowledge according to APA status. In multivariable analysis, predictors significantly associated with guideline-concordant prescribing were having the pharmacist interact as part of an interprofessional team (p = 0.04) and direct OAC (DOAC) self-efficacy (confidence in ability to extend, adapt, initiate or alter prescriptions; p = 0.02). Barriers to prescribing OAC for APA pharmacists included a lack of AF and DOAC knowledge and preference for consulting the physician first, but these same pharmacists also identified difficulty in contacting the physician as a major barrier. Interpretation and Conclusion: Community pharmacists can identify patients who would benefit from stroke prevention therapy in AF. However, physician collaboration and further training on AF and guidelines for prescribing OAC are needed. PMID:29317937

Management of major bleedings during anticoagulant treatment with the oral direct thrombin inhibitor ximelagatran or warfarin.

PubMed

Fernlöf, Gunilla; Sjöström, Britta M; Lindell, Klas M; Wall, Ulrika E

2009-12-01

Several new oral anticoagulants are currently investigated in phase III programmes, mainly with inhibition of factor Xa or thrombin as their pharmacological target. Advantages are expected with these new drugs compared with vitamin K antagonists, but one potential drawback is the lack of specific antidotes. During the clinical studies with ximelagatran, an oral direct thrombin inhibitor withdrawn due to hepatic side effects, investigators were instructed to manage bleedings with routine measures. We have retrospectively tried to assess whether this was sufficient or whether there was a need for reversal strategies. The study population consisted of patients with major bleedings in three long-term studies (104 ximelagatran, 155 warfarin). All individual patient narratives were reviewed with respect to management of the bleeding. Complementary data were retrieved from the data-based case report forms. Approximately, two of three of the patients in both groups were subject to some kind of treatment. One-third (1/3) in both groups had transfusions documented and/or received specific medication. Vitamin K was given more often to warfarin patients. Two ximelagatran patients received prothrombin complex (four-factor concentrate), but one was a patient with a severe hepatopathy suspected to be drug-induced. Overall, the case descriptions did not reveal any apparent differences in the course of events between groups. We found no indications that the lack of an antidote posed a clinical problem in patients treated with ximelagatran as compared with warfarin. The relatively short half-life of melagatran, the active metabolite of ximelagatran, may have contributed to these results.

Budd-Chiari syndrome

PubMed Central

Martens, Pieter

2015-01-01

Budd-Chiari syndrome (BCS) is a rare and potentially life-threatening disorder characterized by obstruction of the hepatic outflow tract at any level between the junction of the inferior vena cava with the right atrium and the small hepatic veins. In the West, BCS is a rare hepatic manifestation of one or more underlying prothrombotic risk factors. The most common underlying prothrombotic risk factor is a myeloproliferative disorder, although it is now recognized that almost half of patients have multiple underlying prothrombotic risk factors. Clinical manifestations can be diverse, making BCS a possible differential diagnosis of many acute and chronic liver diseases. The index of suspicion should be very low if there is a known underlying prothrombotic risk factor and new onset of liver disease. Doppler ultrasound is sufficient for confirming the diagnosis, although tomographic imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) is often necessary for further treatment and discussion with a multidisciplinary team. Anticoagulation is the cornerstone of the treatment. Despite the use of anticoagulation, the majority of patients need additional (more invasive) treatment strategies. Algorithms consisting of local angioplasty, TIPS and liver transplantation have been proposed, with treatment choice dictated by a lack of response to a less-invasive treatment regimen. The application of these treatment strategies allows for a five-year survival rate of 90%. In the long term the disease course of BCS can sometimes be complicated by recurrence, progression of the underlying myeloproliferative disorder, or development of post-transplant lymphoma in transplant patients. PMID:26668741

Pathophysiology, management and treatment of smoke inhalation injury

PubMed Central

Rehberg, Sebastian; Maybauer, Marc O; Enkhbaatar, Perenlei; Maybauer, Dirk M; Yamamoto, Yusuke; Traber, Daniel L

2009-01-01

Smoke inhalation injury continues to increase morbidity and mortality in burn patients in both the third world and industrialized countries. The lack of uniform criteria for the diagnosis and definition of smoke inhalation injury contributes to the fact that, despite extensive research, mortality rates have changed little in recent decades. The formation of reactive oxygen and nitrogen species, as well as the procoagulant and antifibrinolytic imbalance of alveolar homeostasis, all play a central role in the pathogenesis of smoke inhalation injury. Further hallmarks include massive airway obstruction owing to cast formation, bronchospasm, the increase in bronchial circulation and transvascular fluid flux. Therefore, anticoagulants, antioxidants and bronchodilators, especially when administered as an aerosol, represent the most promising treatment strategies. The purpose of this review article is to provide an overview of the pathophysiological changes, management and treatment options of smoke inhalation injury based on the current literature. PMID:20161170

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration.

PubMed

Wong, Y M; Quek, Y-N; Tay, J C; Chadachan, V; Lee, H K

2011-10-01

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was achieved appropriately and efficiently without compromising patient's safety. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

PubMed Central

Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

2015-01-01

Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing embolisms in patients with AF, as the risk of bleeding is not increased. PMID:25634169

Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

PubMed

Sherwood, Matthew W; Douketis, James D; Patel, Manesh R; Piccini, Jonathan P; Hellkamp, Anne S; Lokhnygina, Yuliya; Spyropoulos, Alex C; Hankey, Graeme J; Singer, Daniel E; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Becker, Richard C

2014-05-06

During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

PubMed Central

Sherwood, Matthew W.; Douketis, James D.; Patel, Manesh R.; Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Spyropoulos, Alex C.; Hankey, Graeme J.; Singer, Daniel E.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; Becker, Richard C.

2014-01-01

Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P=0.32). Conclusions TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767. PMID:24552831

Warfarin Safety: A Cross-Sectional Study of the Factors Associated with the Consumption of Medicinal Plants in a Brazilian Anticoagulation Clinic.

PubMed

Leite, Paula Mendonça; de Freitas, Aline A; Mourão, Aline de O Magalhães; Martins, Maria A P; Castilho, Rachel O

2018-06-01

The aim of this study was to analyze factors associated with the consumption of medicinal plants by patients being treated with warfarin in a Brazilian anticoagulation clinic and to study the safety of medicinal plant use in patients on warfarin therapy. The study was performed as an observational cross-sectional analysis. Study participants were outpatients on long-term warfarin therapy for at least 2 months for atrial fibrillation or prosthetic cardiac valves. Interviews were carried out concerning information about the habits of medicinal herb consumption, and logistic regression analysis was performed to identify factors associated with the consumption of herbs. The scientific names of the medicinal plants were identified to search for information on the effects on the hemostasis of the interactions between the medicinal herbs reported and warfarin. The mean age of the 273 patients included was 60.8 years; 58.7% were women. Medicinal plants were used by 67% of the participants. No association between demographic and clinical data and the use of medicinal plants was identified. Patients reported a total of 64 different plants, primarily consumed in the form of tea. The plants were mainly used to treat respiratory tract and central nervous system disorders. About 40% of the plants cited have been reported to potentially interfere with the anticoagulation therapy, principally by potentiating the effects of warfarin, which could, increase the risk of bleeding. The use of medicinal plants was highly common and widespread in patients receiving warfarin as an anticoagulation therapy. Univariate analysis of variables associated with the consumption of herbs showed no statistically significant difference in the consumption of medicinal plants for any of the sociodemographic and clinical data. The medicinal plants that were reportedly consumed by the patients could affect hemostasis. This study reinforces the need for further studies evaluating the habits of patients consuming medicinal plants and their clinical implications, and will help to design strategies to manage the risks associated with warfarin-herbal interactions.

Management of acute lower extremity deep venous thrombosis in a patient with duplicated inferior vena cava and contraindication to anticoagulation: case and review of the literature

PubMed Central

Patel, Shrinil; Cheema, Anmol; Karawadia, Tejas; Carson, Michael

2018-01-01

Duplication of the inferior vena cava (DIVC) is an uncommon embryological anatomic phenomenon. We report a 63-year-old woman with extensive right leg deep vein thrombosis who required an IVC filter due to contraindications for anticoagulation, but was found to have DIVC which required the placement of two IVC filters with good result. This report will review and summarise past reports of DIVC management to provide a guide for future clinicians, and review the embryological development, diagnosis and IVC filter placement options as they are based on the type of anatomic malformation encountered. PMID:29866665

Use of Oral Anticoagulant Therapy in Older Adults with Atrial Fibrillation after Acute Ischemic Stroke

PubMed Central

McGrath, Emer R.; Go, Alan S.; Chang, Yuchiao; Borowsky, Leila H.; Fang, Margaret C.; Reynolds, Kristi; Singer, Daniel E.

2016-01-01

Objective To explore barriers to anticoagulation among older atrial fibrillation (AF) patients at high risk for stroke and identify opportunities where interventions might increase use of oral anticoagulants (OAC). Design Retrospective cohort study Setting Two large community-based AF cohorts Participants 1405 patients (mean age 79 years) with ischemic stroke surviving hospitalization. Measurements Using structured chart review, we identified reasons for non-use of OACand assessed one-year post-stroke survival. Logistic regression identified correlates of OAC non-use. Results The median CHA2DS2-VASc score was 5, yet 44% of patients were not prescribed OAC at discharge. The most frequent (non-mutually exclusive) physician reasons for non-prescription of OAC included fall risk (26.7%), poor prognosis (19.3%), bleeding history (17.1%), patient/family refusal (14.9%), older age (11.0%) and dementia (9.4%). Older age (OR 8.96, 95% CI 5.01–16.04 for age ≥85 vs. age <65 years) and increased disability (OR 12.58, 95% CI 5.82–27.21 for severe vs. no deficit) were the most important independent predictors of non-use of OAC. By one year, 42.5% of those not receiving OAC at discharge had died versus 19.1% of those receiving OAC (p<0.0001), far higher than recurrent stroke rates. Conclusion Despite very high stroke risk, over 40% of patients were not discharged on OAC. Dominant reasons included fall risk, poor prognosis, older age, and dementia. These patients’ elevated 1-year mortality rate confirmed their high level of comorbidity. Future work to improve outcomes and clinical decisions regarding anticoagulation in this patient population should focus on: mitigation of fall risk, better assessment and decision tools for determining risk/benefit in individual patients, and determining whether newer anticoagulants are safer in complex elderly and/or frail patients. PMID:28039855

Novel anticoagulants for stroke prevention in atrial fibrillation: a systematic review of cost-effectiveness models.

PubMed

Limone, Brendan L; Baker, William L; Kluger, Jeffrey; Coleman, Craig I

2013-01-01

To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF. Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.

Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Systematic Review of Cost-Effectiveness Models

PubMed Central

Limone, Brendan L.; Baker, William L.; Kluger, Jeffrey; Coleman, Craig I.

2013-01-01

Objective To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF). Patients and Methods We searched Medline, Embase, NHSEED and HTA databases and the Tuft’s Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation) models of newer agents for SPAF. Results Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%), European (39%) and Canadian (17%) perspectives. Models typically assumed patients between 65–73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER) for a newer anticoagulant (dabigatran 110 mg (n = 4)/150 mg (n = 2); rivaroxaban (n = 1)) vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547–$86,000 for dabigatran 150 mg, $20,713–$150,000 for dabigatran 110 mg, $4,084–$21,466 for sequentially-dosed dabigatran and $23,065–$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400–$25,059) vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. Conclusions Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent. PMID:23626785

A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: treating critical limb ischemia like acute coronary syndrome.

PubMed

Allie, David E; Hebert, Chris J; Lirtzman, Mitchell D; Wyatt, Charles H; Keller, V Antoine; Khan, Mohamed H; Khan, Muhammad A; Fail, Peter S; Vivekananthan, Krishnamoorthy; Allie, Sonja E; Mitran, Elena V; Chaisson, Gary; Stagg, Samuel J; Allie, Adam A; McElderry, Michael W; Barker, Esmond A; Walker, Craig M

2005-08-01

The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI). Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE). Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively. The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.

Atrial fibrillation among African Americans, Hispanics and Caucasians: clinical features and outcomes from the AFFIRM trial.

PubMed

Bush, David; Martin, Lisa W; Leman, Robert; Chandler, Mary; Haywood, L Julian

2006-03-01

The Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study concluded that rate control with anticoagulation was equivalent overall to rhythm control with cardioversion for long-term survival and that anticoagulation reduced the risk of stroke. We compared baseline and follow-up data for three ethnic groups: Caucasians (n=3,599), African Americans (n=265) and Hispanics (n=132). Caucasians were older and more likely male, African Americans were more likely female and hypertensive, and Hispanics had higher prevalence of cardiomyopathy. Survival was better for rate control than rhythm control in Caucasians, equivalent in African Americans and better for rhythm control in Hispanics. Outcomes may be influenced by differential baseline characteristics, but low numbers of African Americans and Hispanics warrant caution in data interpretation. The AFFIRM study compared a rate-control strategy to a rhythm-control strategy for the treatment of atrial fibrillation (AF) in patients at high risk for stroke or death. It concluded that the rhythm-control strategy offered no survival advantage, and it also confirmed the value of anticoagulation to prevent complications of AF. Data have not previously been available for specific racial ethnic populations. We compared baseline and follow-up data for the patients randomized to rate-control versus rhythm-control in three population groups-Caucasian, African-American and Hispanic. Among 4,060 total patients, 3,599 were Caucasian, 265 were African-American and 132 were Hispanic. At baseline, Caucasians were older and had a higher percentage of males, normal ejection fractions, AF as their only cardiac diagnosis, a prior antiarrhythmic drug failure and less congestive heart failure. African Americans were more likely to be female, had more hypertension and qualified for the study with a first episode of AF, compared to Caucasians. Hispanics had more cardiomyopathy at baseline than Caucasians. Overall survival in Caucasians at five years for the rate-control and rhythm-control groups was 78.9% vs. 76.4%, respectively (p=0.04); for African Americans, 79.0% vs. 69.4% (p=0.22); and for Hispanics, 66.5% vs. 83.9% (p=0.01). Overall, survival was not different between the three populations. However, lower rates of event-free survival were recorded for Hispanics and for African Americans (p=0.0182). Different survival rates were found for rate-control versus rhythm-control in African-American and Hispanic patients, compared to Caucasian. These findings may be influenced by differences in baseline characteristics, but must be interpreted with caution because of the small sample sizes for African-American and Hispanic participants.

Bleeding events associated with novel anticoagulants: a case series.

PubMed

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

PubMed

Gunaratne, Ruwan; Kumar, Shekhar; Frederiksen, James W; Stayrook, Steven; Lohrmann, Jens L; Perry, Kay; Bompiani, Kristin M; Chabata, Charlene V; Thalji, Nabil K; Ho, Michelle D; Arepally, Gowthami; Camire, Rodney M; Krishnaswamy, Sriram; Sullenger, Bruce A

2018-06-04

Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.

2017 Scientific Sessions Sol Sherry Distinguished Lecture in Thrombosis: Factor XI as a Target for New Anticoagulants.

PubMed

Weitz, Jeffrey I; Fredenburgh, James C

2018-02-01

The goal of anticoagulant therapy is to attenuate thrombosis without compromising hemostasis. Although the direct oral anticoagulants are associated with less intracranial hemorrhage than vitamin K antagonists, bleeding remains their major side effect. Factor XI has emerged as a promising target for anticoagulants that may be safer than those currently available. The focus on factor XI stems from epidemiological evidence of its role in thrombosis, the observation of attenuated thrombosis in factor XI-deficient mice, identification of novel activators, and the fact that factor XI deficiency is associated with only a mild bleeding diathesis. Proof-of-concept comes from the demonstration that compared with enoxaparin, factor XI knockdown reduces venous thromboembolism without increasing bleeding after elective knee arthroplasty. This article rationalizes the selection of factor XI as a target for new anticoagulants, reviews the agents under development, and outlines a potential path forward for their development. © 2017 American Heart Association, Inc.

Quality of anticoagulation control: do race and language matter?

PubMed

Bhandari, Vijay Kumar; Wang, Frances; Bindman, Andrew B; Schillinger, Dean

2008-02-01

No studies have evaluated the quality of anticoagulation control among populations characterized by low socioeconomic status, diverse racial and ethnic backgrounds, or limited English proficiency. We conducted a retrospective cohort study to evaluate the effects of race/ethnicity and language on anticoagulation outcomes among patients (N=864) receiving continuous anticoagulation services at a university-affiliated public hospital. White/non-Hispanic patients made up 24%, Asian/Pacific Islanders 33%, Hispanics 22%, African Americans 18%. English (63%), Spanish, (14%), and Cantonese (13%) were the most common languages. Mean time in therapeutic range (TTR) was 43%. After adjustment, TTR was lower for African Americans than for Whites (absolute difference, -8.7%, p< .001) and for Spanish-speaking than for English-speaking Hispanics (absolute difference, -7.2%, p< .05). There were no differences between Asian/Pacific Islanders and Whites, nor between Cantonese-speaking and English-speaking Asian/Pacific Islanders. Future research should examine mechanisms by which race/ethnicity and language affect quality of anticoagulation and evaluate programs to improve treatment in diverse communities.

To Bleed or Not to Bleed: That is the Question. The Side Effects of Apixaban.

PubMed

Ciccone, Marco Matteo; Zito, Annapaola; Devito, Fiorella; Maiello, Maria; Palmiero, Pasquale

2018-01-01

Apixaban is a new oral anticoagulant (NOACs: Novel Oral Anticoagulant), like dabigatran, rivaroxaban, and edoxaban. All of them are prescribed to patients with non valvular atrial fibrillation or venous thromboembolism, to replace warfarin, because of the lower probability of bleeding, however they can cause bleeding by themselves. Bleeding is an adverse event in patients taking anticoagulants. It is associated with a significant increase of morbidity and risk of death. However, these drugs should be used only for the time when anticoagulation is strictly required, especially when used for preventing deep vein thrombosis. Prolonged use increases the risk of bleeding. In the ARISTOTLE Trial Apixaban, compared with warfarin, was associated with a lower rate of intracranial hemorrhages and less adverse consequences following extracranial hemorrhage. Many physicians still have limited experience with new oral anticoagulants and about bleeding risk managment. We reviewed the available literature on extracranial and intracranial bleeding concerning apixaban. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A rapid method for isolation and purification of an anticoagulant from Whitmania pigra.

PubMed

Zhong, Shan; Cui, Zheng; Sakura, Naoki; Wang, Dong; Li, Jianlin; Zhai, Yan

2007-05-01

Whitmania pigra is common in China and has been used as a traditional Chinese anticoagulant medicine for years, but its effective components are unknown to scientists. In this article we report a rapid method for isolation and purification of an anticoagulant from W. pigra for the first time. An acetone-water extract of W. pigra was subjected to anion-exchange chromatography on a Sephadex DEAE A-50 column, and gel permeation chromatography on Sephadex G-25 and Sephadex LH-20 columns successively, which afforded a fraction with potent anticoagulant activity. An anticoagulant was isolated and purified from this fraction by reversed-phase high-performance liquid chromatography (RP-HPLC). It was identified as a single pure substance by RP-HPLC and sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). This component was named whitmanin and its molecular weight was determined as 8608 Da by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF-MS). (c) 2006 John Wiley & Sons, Ltd.

Anterior mediastinal haematoma and left haemothorax on well-controlled oral anticoagulant therapy.

PubMed Central

Abaskaron, M.; Peterson, G.; Huang, T. Y.

1983-01-01

An anterior mediastinal haematoma and left haemothorax developed in a hypertensive diabetic patient on oral anticoagulant therapy. This occurred in spite of well-controlled anticoagulation and the absence of other evidence of systemic bleeding. Angiography and daily chest X-ray follow-up were not only sufficient to confirm the diagnosis, but also avoided hazardous interventional procedures. Images Fig. 1a Fig. 1b PMID:6844193

Effect of magnetic bracelets on the coagulation and anticoagulation systems of the blood of patients with hypertension

NASA Technical Reports Server (NTRS)

Bublis, V. V.; Zabrodina, L. V.; Platonova, A. T.; Meyerova, Y. A.

1974-01-01

The data which have been obtained on the influence of magnetic bracelets on the coagulation and anticoagulation systems of the blood indicate that the wearing of magnetic bracelets results in a decrease in the coagulation activity of the blood and an increase in the activity of the anticoagulation system. These changes must be viewed as favorable for patients with cardiovascular pathology.

Dabigatran and kidney disease: a bad combination.

PubMed

Knauf, Felix; Chaknos, C Michael; Berns, Jeffrey S; Perazella, Mark A

2013-09-01

Dabigatran is an oral direct thrombin inhibitor widely used to prevent and treat various thromboembolic complications. An advantage of this agent over other anticoagulants is that routine laboratory monitoring and related dose adjustments are considered unnecessary. A major disadvantage is the absence of a reliable means of reversing its anticoagulant effect. After U.S. Food and Drug Administration approval, recently emerged data suggest a higher bleeding risk with dabigatran, especially in the elderly. Clinicians are thus faced with caring for patients with serious bleeding events without readily available tests to measure drug levels or the anticoagulant effects of dabigatran and without effective antidotes to rapidly reverse the anticoagulant effect. On the basis of dabigatran's pharmacokinetic profile, hemodialysis and continuous renal replacement therapy have been used to remove dabigatran with the hope, still unproven, that this would rapidly reverse the anticoagulant effect and reduce bleeding in patients with normal and those with reduced kidney function. However, the best clinical approach to the patient with serious bleeding is not known, and the risks of placing a hemodialysis catheter in an anticoagulated patient can be substantial. This article reviews this issue, addressing clinical indications, drug pharmacokinetics, clinical and laboratory monitoring tests, and dialytic and nondialytic approaches to reduce bleeding in dabigatran-treated patients.

Adherence to Guidelines for Oral Anticoagulation after Venous Thrombosis and Pulmonary Embolism

PubMed Central

Ganz, David A; Glynn, Robert J; Mogun, Helen; Knight, Eric L; Bohn, Rhonda L; Avorn, Jerry

2000-01-01

OBJECTIVE Guidelines for oral anticoagulation after deep venous thrombosis (DVT) or pulmonary embolism (PE) have recommended that patients be anticoagulated for at least 3 months after hospital discharge. We sought to determine whether this recommendation was being followed and what patient characteristics predict a shorter than recommended duration of therapy. DESIGN Retrospective cohort study using linked health care claims data. SETTING Routine clinical practice. PATIENTS Five hundred seventy-three members of New Jersey's Medicaid or Pharmacy Assistance for the Aged and Disabled programs aged 65 years and older who were hospitalized for DVT or PE between January 1, 1991 and June 30, 1994. RESULTS Of the 573 patients, 129 (23%) filled prescriptions covering less than 90 days of oral anticoagulant therapy. In multivariate models, African-American race was associated with an increased risk of a shorter than recommended duration of therapy (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14 to 3.08), but age and gender were not. Patients who used anticoagulants in the year prior to admission were less likely to have a short duration of therapy (OR, 0.30; 95% CI, 0.12 to 0.78), than were patients with PE (OR, 0.58; 95% CI, 0.38 to 0.88). CONCLUSIONS Nearly a quarter of those anticoagulated following DVT or PE received therapy for less than the recommended length of time after hospital discharge, with African Americans more likely to have a shorter than recommended course of treatment. Further research is needed to evaluate the causes of shorter than recommended duration of therapy and racial disparities in anticoagulant use. PMID:11119169

Exploration of adherence and patient experiences with DOACs one year after switching from vitamin-K antagonists- insights from the switching study.

PubMed

Bartoli-Abdou, John K; Patel, Jignesh P; Crawshaw, Jacob; Vadher, Bipin; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen; Auyeung, Vivian

2018-02-01

Current UK and European guidelines recommend anticoagulated patients prescribed warfarin with time in therapeutic range (TTR) <65% be considered for DOAC therapy. There has been considerable concern that adherence with DOACs may be poor compared with warfarin. Little is known about the patient experience of switching from warfarin to DOAC and how patients manage their DOAC long term. Our aim was to conduct focus groups exploring patient's previous experiences with warfarin, their current experience with DOACs, their adherence to DOACs and the long-term service provision they envisage. Patients enrolled on the Switching Study who had been switched from warfarin to a DOAC >1year previously were invited to participate in focus groups. Two focus groups for atrial fibrillation (AF) and two for secondary prevention of venous thromboembolism (VTE) patients were held at anticoagulation clinics in South London, UK. Data was analysed using framework analysis to extract dominant themes. Five VTE patients and 15 AF patients attended the focus groups. Dominant themes that emerged were: indication specific anticoagulation prioritisation, warfarin as a necessary inconvenience, DOACs as the anticoagulant of choice, concerns regarding DOAC monitoring, high adherence to DOACs and desire for long-term access to specialist anticoagulation services. VTE patients prioritised anticoagulation over other therapies whereas AF patients did not. All participants reported high levels of adherence to DOACs. Patients derived confidence from long-term management in specialist anticoagulation clinics stating a preference to be managed in such a service. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world) perspective

PubMed Central

2011-01-01

Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation. PMID:21794130

The scope and value of an anticoagulation stewardship program at a community teaching hospital.

PubMed

Wychowski, Maura K; Ruscio, Christina I; Kouides, Peter A; Sham, Ronald L

2017-04-01

To report the impact of an inpatient anticoagulation stewardship program at a community hospital to promote optimal anticoagulant use. The anticoagulation team (ACT) stewardship program consists of two clinical pharmacists and hematologists to provide oversight of anticoagulants, high cost reversal agents including prothrombin complex concentrate (PCC, Kcentra™), and heparin-induced thrombocytopenia (HIT) management. Intervention data and number of charts reviewed were collected. Average cost avoidance data was applied to ACT interventions to estimate cost savings. The PCC analysis was conducted via retrospective chart review during the pre-intervention period. Prospective monitoring continued in the post-intervention period to determine the percentage of PCC use within the institution's guidelines or approved by ACT or hematology. A total of 19,445 patient charts were reviewed, and 1930 (10%) contained stewardship opportunity. Of the interventions, 71% were provided to the medical service and 22% to surgical services with acceptance rates of 91 and 83%, respectively. Intervention cost-avoidance calculated to be $694,217. Regarding HIT interventions, 52% of interventions involved pharmacokinetic/pharmacodynamics optimization in 18 patients with suspected or confirmed HIT. Regarding PCC use, 55.8% of PCC orders were considered inappropriate in the pre-invention period versus 2.6% post-intervention. Appropriate PCC doses per month post-intervention were consistent with pre-intervention doses (7.67 vs. 6.73, respectively). The projected annual PCC cost savings is $385,473. The overall estimated financial impact of ACT is $799,690 saved. Implementation of an anticoagulation stewardship program reduced costs and improved clinical outcomes. It is also expected that anticoagulant optimization and provider education improved overall safety.

MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

PubMed

Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

2018-03-16

Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

PubMed

Hofmann, Eveline; Faller, Nicolas; Limacher, Andreas; Méan, Marie; Tritschler, Tobias; Rodondi, Nicolas; Aujesky, Drahomir

2016-01-01

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss.

PubMed

Mankee, Anil; Petri, Michelle; Magder, Laurence S

2015-01-01

Multiple factors, including proteinuria, antiphospholipid syndrome, thrombocytopenia and hypertension, are predictive of pregnancy loss in systemic lupus erythematosus (SLE). In the PROMISSE study of predictors of pregnancy loss, only a battery of lupus anticoagulant tests was predictive of a composite of adverse pregnancy outcomes. We examined the predictive value of one baseline lupus anticoagulant test (dilute Russell viper venom time) with pregnancy loss in women with SLE. From the Hopkins Lupus Cohort, there were 202 pregnancies from 175 different women after excluding twin pregnancies and pregnancies for which we did not have a first trimester assessment of lupus anticoagulant. We determined the percentage of women who had a pregnancy loss in groups defined by potential risk factors. The lupus anticoagulant was determined by dilute Russell viper venom time with appropriate mixing and confirmatory testing. Generalised estimating equations were used to calculate p values, accounting for repeated pregnancies in the same woman. The age at pregnancy was <20 years (2%), 20-29 (53%), 30-39 (41%) and >40 (3%). 55% were Caucasian and 34% African-American. Among those with lupus anticoagulant during the first trimester, 6/16 (38%) experienced a pregnancy loss compared with only 16/186 (9%) of other pregnancies (p=0.003). In addition, those with low complement or higher disease activity had a higher rate of pregnancy loss than those without (p=0.049 and 0.005, respectively). In contrast, there was no association between elevated anticardiolipin in the first trimester and pregnancy loss. The strongest predictor of pregnancy loss in SLE in the first trimester is the lupus anticoagulant. In addition, moderate disease activity by the physician global assessment and low complement measured in the first trimester were predictive of pregnancy loss. These data suggest that treatment of the lupus anticoagulant could be considered, even in the absence of history of pregnancy loss.

Multinational development of a questionnaire assessing patient satisfaction with anticoagulant treatment: the 'Perception of Anticoagulant Treatment Questionnaire' (PACT-Q©)

PubMed Central

Prins, Martin H; Marrel, Alexia; Carita, Paulo; Anderson, David; Bousser, Marie-Germaine; Crijns, Harry; Consoli, Silla; Arnould, Benoit

2009-01-01

Background The side effects and burden of anticoagulant treatments may contribute to poor compliance and consequently to treatment failure. A specific questionnaire is necessary to assess patients' needs and their perceptions of anticoagulant treatment. Methods A conceptual model of expectation and satisfaction with anticoagulant treatment was designed by an advisory board and used to guide patient (n = 31) and clinician (n = 17) interviews in French, US English and Dutch. Patients had either atrial fibrillation (AF), deep venous thrombosis (DVT), or pulmonary embolism (PE). Following interviews, three PACT-Q language versions were developed simultaneously and further pilot-tested by 19 patients. Linguistic validations were performed for additional language versions. Results Initial concepts were developed to cover three areas of interest: 'Treatment', 'Disease and Complications' and 'Information about disease and anticoagulant treatment'. After clinician and patient interviews, concepts were further refined into four domains and 17 concepts; test versions of the PACT-Q were then created simultaneously in three languages, each containing 27 items grouped into four domains: "Treatment Expectations" (7 items), "Convenience" (11 items), "Burden of Disease and Treatment" (2 items) and "Anticoagulant Treatment Satisfaction" (7 items). No item was deleted or added after pilot testing as patients found the PACT-Q easy to understand and appropriate in length in all languages. The PACT-Q was divided into two parts: the first part to measure the expectations and the second to measure the convenience, burden and treatment satisfaction, for evaluation prior to and after anticoagulant treatment, respectively. Eleven additional language versions were linguistically validated. Conclusion The PACT-Q has been rigorously developed and linguistically validated. It is available in 14 languages for use with thromboembolic patients, including AF, PE and DVT patients. Its validation and psychometric properties have been tested and are presented in a separate manuscript. PMID:19196486

[Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

PubMed

Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

2017-10-01

Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Peri-operative Adverse Outcomes in Patients with Atrial Fibrillation Taking Warfarin or Edoxaban: Analysis of the ENGAGE AF-TIMI 48 Trial.

PubMed

Douketis, James D; Murphy, Sabina A; Antman, Elliott M; Grip, Laura T; Mercuri, Michele F; Ruff, Christian T; Weitz, Jeffrey I; Braunwald, Eugene; Giugliano, Robert P

2018-06-01

 Peri-operative management of anticoagulated patients with atrial fibrillation (AF) is challenging. To gain information on the peri-operative management of edoxaban, we compared outcomes in patients on warfarin or edoxaban enrolled in ENGAGE AF-TIMI 48 who underwent a surgery or invasive procedure.  Data from patients undergoing their first surgery/procedure were analysed and results compared by anticoagulant (warfarin vs. higher- or lower-dose edoxaban regimen [HDER and LDER, respectively]). Patients were classified by procedural management: anticoagulant interrupted (last dose 4-10 days pre-procedure) or anticoagulant continued (last dose ≤ 3 days pre-procedure). Stroke/systemic embolism (SSE), major bleeding (MB), MB or clinically relevant non-MB (CRNMB) and death were assessed from 7 days pre- until 30 days post-procedure. The chi-square test was used to compare outcomes across treatment groups.  A total of 7,193 patients (34%) underwent surgery/procedure: 3,116 had anticoagulant interrupted, 4,077 had anticoagulant continued. Among patients on warfarin, HDER and LDER who had anticoagulant interrupted, rates of SSE were 0.6, 0.5 and 0.9% ( p  = 0.53), rates of MB were 1.0, 1.2 and 1.1% ( p  = 0.94) and rates of MB or CRNMB were 3.9, 4.2 and 3.6% ( p  = 0.78); among patients on warfarin, HDER and LDER who had anticoagulant continued, rates of SSE were 1.1, 0.7 and 0.9% ( p  = 0.51), rates of MB were 3.6, 2.6 and 2.4% ( p  = 0.13) and rates of MB or CRNMB were 8.5, 7.9 and 6.6% ( p  = 0.17).  In patients requiring surgery/procedure in ENGAGE AF-TIMI 48, peri-operative rates of SSE, MB and death were not significantly different in patients who received edoxaban or warfarin. Schattauer GmbH Stuttgart.

Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Rushton-Smith, Sophie K; Goldhaber, Samuel Z; Fitzmaurice, David A; Mantovani, Lorenzo G; Goto, Shinya; Haas, Sylvia; Bassand, Jean-Pierre; Camm, Alan John; Ambrosio, Giuseppe; Janský, Petr; Al Mahmeed, Wael; Oh, Seil; van Eickels, Martin; Raatikainen, Pekka; Steffel, Jan; Oto, Ali; Kayani, Gloria; Accetta, Gabriele; Kakkar, Ajay K

2015-03-01

Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92-1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk. http://www.clinicaltrials.gov. Unique identifier: NCT01090362. © 2015 American Heart Association, Inc.

Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling.

PubMed

Connock, M; Stevens, C; Fry-Smith, A; Jowett, S; Fitzmaurice, D; Moore, D; Song, F

2007-10-01

To examine the clinical effectiveness and cost-effectiveness of self-testing and self-management of oral anticoagulation treatment compared with clinic-based monitoring. Major electronic databases were searched up to September 2005. A systematic review was undertaken of relevant data from selected studies. Results about complication events and deaths were pooled in meta-analyses using risk difference (RD) as the outcome statistic. Heterogeneity across trials and possible publication bias were statistically measured. Subgroup analyses (post hoc) were conducted to compare results of self-testing versus self-management, low versus high trial quality, trials conducted in the UK versus trials in other countries and industry versus other sponsors. A Markov-type, state-transition model was developed. Stochastic simulations using the model were conducted to investigate uncertainty in estimated model parameters. In the 16 randomised and eight non-randomised trials selected, patient self-monitoring of oral anticoagulation therapy was found to be more effective than poor-quality usual care provided by family doctors and as effective as good-quality specialised anticoagulation clinics in maintaining the quality of anticoagulation therapy. There was no significant RD of major bleeding events between patient self-monitoring and usual care controls and pooled analyses found that compared with primary care or anticoagulation control (AC) clinics, self-monitoring was statistically significantly associated with fewer thromboembolic events. However, the reduction in complication events and deaths was not consistently associated with the improvement of AC; in some trials this may be due to alternative explanations, including patient education and patient empowerment. Also, the improved AC and the reduction of major complications and deaths by patient self-monitoring were mainly observed in trials conducted outside the UK. According to UK-specific data, for every 100 eligible patients, 24% would agree to conduct self-monitoring, 17 of the 24 patients (70%) could be successfully trained and able to carry out self-monitoring and only 14 of these (80%) would conduct long-term self-monitoring. Seven cost-effectiveness studies were identified and the study that provided the most relevant UK data found that patient self-management was more expensive than current routine care (417 pounds versus 122 pounds per patient-year) and concluded that using a cost-effectiveness threshold of 30,000 pounds per quality-adjusted life-year (QALY) gained, patient self-management does not appear to be cost-effective. De novo modelling for this report found that the incremental cost per QALY gained by patient self-monitoring is 122,365 pounds over 5 years and 63,655 pounds over 10 years. The estimated probability that patient self-monitoring is cost-effective (up to 30,000 pounds/QALY) is 44% over a 10-year period. Wide adoption of patient self-monitoring of anticoagulation therapy would cost the NHS an estimated additional 8-14 million pounds per year. For selected and successfully trained patients, self-monitoring is effective and safe for long-term oral anticoagulation therapy. In general, patient self-management (PSM) is unlikely to be more cost-effective than the current specialised anticoagulation clinics in the UK; self-monitoring may enhance the quality of life for some patients who are frequently away from home, who are in employment or education, or those who find it difficult to travel to clinics. Further research is needed into alternative dosing regimes, the clinical effectiveness and cost-effectiveness of patient education and training in long-term oral anticoagulation therapy, UK-relevant cost-effectiveness, the effectiveness of PSM in children, and the potential future developments of near-patient testing devices.

Simulation in an Undergraduate Nursing Pharmacology Course: A Pilot Study.

PubMed

Tinnon, Elizabeth; Newton, Rebecca

This study examined the effectiveness of simulation as a method of teaching pharmacological concepts to nursing students; perceptions of satisfaction with simulation as a teaching strategy were also evaluated. Second-semester juniors participated in three simulations and completed the National League for Nursing Student Satisfaction and Self-Confidence in Learning Questionnaire and the Student Evaluation of Educational Quality Survey; a control group received traditional lectures. A unit exam on anticoagulant therapy content was administered to measure effectiveness. Findings support that simulation is as effective as traditional lecture for an undergraduate pharmacology course.

Left Atrial Appendage Exclusion for Atrial Fibrillation

PubMed Central

Syed, Faisal F.; DeSimone, Christopher V.; Friedman, Paul A.; Asirvatham, Samuel J.

2015-01-01

SYNOPSIS Percutaneous left atrial appendage (LAA) closure is increasingly being used as a treatment strategy to prevent stroke in patients with atrial fibrillation (AF) who have contraindications to anticoagulants. A number of approaches and devices have been developed in the last few years, each with their own unique set of advantages and disadvantages. We review the published studies on surgical and percutaneous approaches to LAA closure; focusing on stroke mechanisms in AF, LAA structure and function relevant to stroke prevention, practical differences in procedural approach, and clinical considerations surrounding management. PMID:25443240

Developing a Highly Active Blood Anticoagulant—a Heparin Complex with Glutamic Acid—by Simulating Chemical Equilibria Based on pH-Metric Data

NASA Astrophysics Data System (ADS)

Nikolaeva, L. S.; Semenov, A. N.

2018-02-01

The anticoagulant activity of high-molecular-weight heparin is increased by developing a new highly active heparin complex with glutamate using the thermodynamic model of chemical equilibria based on pH-metric data. The anticoagulant activity of the developed complexes is estimated in the pH range of blood plasma according to the drop in the calculated equilibrium Ca2+ concentration associated with the formation of mixed ligand complexes of Ca2+ ions, heparin (Na4hep), and glutamate (H2Glu). A thermodynamic model is calculated by mathematically modelling chemical equilibria in the CaCl2-Na4hep-H2Glu-H2O-NaCl system in the pH range of 2.30 ≤ pH ≤ 10.50 in diluted saline that acts as a background electrolyte (0.154 M NaCl) at 37°C and initial concentrations of the main components of ν × 10-3 M, where n ≤ 4. The thermodynamic model is used to determine the main complex of the monomeric unit of heparin with glutamate (HhepGlu5-) and the most stable mixed ligand complex of Ca2+ with heparin and glutamate (Ca2hepGlu2-) in the pH range of blood plasma (6.80 ≤ pH ≤ 7.40). It is concluded that the Ca2hepGlu2- complex reduces the Ca2+ concentration 107 times more than the Ca2+ complex with pure heparin. The anticoagulant effect of the developed HhepGlu5- complex is confirmed in vitro and in vivo via coagulation tests on the blood plasma of laboratory rats. Additional antithrombotic properties of the developed complex are identified. The new highly active anticoagulant, HhepGlu5- complex with additional antithrombotic properties, is patented.

Discrepancies between Patients' Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations.

PubMed

Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

2016-01-01

Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers' perceptions of what patients should know, rather than on patients' preferences. To investigate patients' viewpoints on educational needs and preferred modalities of information delivery. We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30-2.46). Pharmacists (1.69, 1.58-1.80), nurses (1.05, 0.95-1.16), and patient associations (0.36, 0.29-0.44), along with group sessions (0.85, 0.75-0.95), the internet (0.77, 0.67-0.88), and delivery of material at the patient's home (1.26, 1.14-1.38), were ranked poorly in terms of delivering educational material. This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.

D-dimer levels over time and the risk of recurrent venous thromboembolism: an update of the Vienna prediction model.

PubMed

Eichinger, Sabine; Heinze, Georg; Kyrle, Paul A

2014-01-02

Patients with unprovoked venous thromboembolism (VTE) can be stratified according to their recurrence risk based on their sex, the VTE location, and D-dimer measured 3 weeks after anticoagulation by the Vienna Prediction Model. We aimed to expand the model to also assess the recurrence risk from later points on. Five hundred and fifty-three patients with a first VTE were followed for a median of 68 months. We excluded patients with VTE provoked by a transient risk factor or female hormone intake, with a natural inhibitor deficiency, the lupus anticoagulant, or cancer. The study end point was recurrent VTE, which occurred in 150 patients. D-dimer levels did not substantially increase over time. Subdistribution hazard ratios (95% confidence intervals) dynamically changed from 2.43 (1.57 to 3.77) at 3 weeks to 2.27 (1.48 to 3.48), 1.98 (1.30 to 3.02) , and 1.73 (1.11 to 2.69) at 3, 9, and 15 months in men versus women, from 1.84 (1.00 to 3.43) to 1.68 (0.91 to 3.10), 1.49 (0.79 to 2.81) , and 1.44 (0.76 to 2.72) in patients with proximal deep vein thrombosis or pulmonary embolism compared with calf vein thrombosis, and from 1.30 (1.07 to 1.58) to 1.27 (1.06 to 1.51), 1.20 (1.02 to 1.41), and 1.13 (0.95 to 1.36) per doubling D-dimer. Using a dynamic landmark competing risks regression approach, we generated nomograms and a web-based calculator to calculate risk scores and recurrence rates from multiple times after anticoagulation. Risk of recurrent VTE after discontinuation of anticoagulation can be predicted from multiple random time points by integrating the patient's sex, location of first VTE, and serial D-dimer measurements.

Management of anticoagulation in hip fractures: A pragmatic approach.

PubMed

Yassa, Rafik; Khalfaoui, Mahdi Yacine; Hujazi, Ihab; Sevenoaks, Hannah; Dunkow, Paul

2017-09-01

Hip fractures are common and increasing with an ageing population. In the United Kingdom, the national guidelines recommend operative intervention within 36 hours of diagnosis. However, long-term anticoagulant treatment is frequently encountered in these patients which can delay surgical intervention. Despite this, there are no set national standards for management of drug-induced coagulopathy pre-operatively in the context of hip fractures.The aim of this study was to evaluate the management protocols available in the current literature for the commonly encountered coagulopathy-inducing agents.We reviewed the current literature, identified the reversal agents used in coagulopathy management and assessed the evidence to determine the optimal timing, doses and routes of administration.Warfarin and other vitamin K antagonists (VKA) can be reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg intravenously to correct coagulopathy.The role of fresh frozen plasma is not clear from the current evidence while prothrombin complex remains a reliable and safe method for immediate reversal of VKA-induced coagulopathy in hip fracture surgery or failed vitamin K treatment reversal.The literature suggests that surgery should not be delayed in patients on classical antiplatelet medications (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be avoided for the latter. However, evidence regarding the use of more novel antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains a largely unexplored area in the context of hip fracture surgery. We suggest treatment protocols based on best available evidence and guidance from allied specialties.Hip fracture surgery presents a common management dilemma where semi-urgent surgery is required. In this article, we advocate an evidence-based algorithm as a guide for managing these anticoagulated patients. Cite this article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events.

PubMed

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs.

New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events

PubMed Central

Mekaj, Ymer H; Mekaj, Agon Y; Duci, Shkelzen B; Miftari, Ermira I

2015-01-01

Despite the discovery and application of many parenteral (unfractionated and low-molecular-weight heparins) and oral anticoagulant vitamin K antagonist (VKA) drugs, the prevention and treatment of venous and arterial thrombotic phenomena remain major medical challenges. Furthermore, VKAs are the only oral anticoagulants used during the past 60 years. The main objective of this study is to present recent data on non-vitamin K antagonist oral anticoagulants (NOACs) and to analyze their advantages and disadvantages compared with those of VKAs based on a large number of recent studies. NOACs are novel direct-acting medications that are selective for one specific coagulation factor, either thrombin (IIa) or activated factor X (Xa). Several NOACs, such as dabigatran (a direct inhibitor of FIIa) and rivaroxaban, apixaban and edoxaban (direct inhibitors of factor Xa), have been used for at least 5 years but possibly 10 years. Unlike traditional VKAs, which prevent the coagulation process by suppressing the synthesis of vitamin K-dependent factors, NOACs directly inhibit key proteases (factors IIa and Xa). The important indications of these drugs are the prevention and treatment of deep vein thrombosis and pulmonary embolisms, and the prevention of atherothrombotic events in the heart and brain of patients with acute coronary syndrome and atrial fibrillation. They are not fixed, and dose-various strengths are available. Most studies have reported that more advantages than disadvantages for NOACs when compared with VKAs, with the most important advantages of NOACs including safety issues (ie, a lower incidence of major bleeding), convenience of use, minor drug and food interactions, a wide therapeutic window, and no need for laboratory monitoring. Nonetheless, there are some conditions for which VKAs remain the drug of choice. Based on the available data, we can conclude that NOACs have greater advantages and fewer disadvantages compared with VKAs. New studies are required to further assess the efficacy of NOACs. PMID:26150723

To mix or not to mix venous blood samples collected in vacuum tubes?

PubMed

Parenmark, Anna; Landberg, Eva

2011-09-08

There are recommendations to mix venous blood samples by inverting the tubes immediately after venipuncture. Though mixing allows efficient anticoagulation in plasma tubes and fast initiation of coagulation in serum tubes, the effect on laboratory analyses and risk of haemolysis has not been thoroughly evaluated. Venous blood samples were collected by venipuncture in vacuum tubes from 50 patients (10 or 20 patients in each group). Four types of tubes and 18 parameters used in routine clinical chemistry were evaluated. For each patient and tube, three types of mixing strategies were used: instant mixing, no mixing and 5 min of rest followed by mixing. Most analyses did not differ significantly in samples admitted to different mixing strategies. Plasma lactate dehydrogenase and haemolysis index showed a small but significant increase in samples omitted to instant mixing compared to samples without mixing. However, in one out of twenty non-mixed samples, activated partial thromboplastin time was seriously affected. These results indicate that mixing blood samples after venipuncture is not mandatory for all types of tubes. Instant mixing may introduce interference for those analyses susceptible to haemolysis. However, tubes with liquid-based citrate buffer for coagulation testing should be mixed to avoid clotting.

Anticoagulant, antiherpetic and antibacterial activities of sulphated polysaccharide from Indian medicinal plant Tridax procumbens L. (Asteraceae).

PubMed

Naqash, Shabeena Yousuf; Nazeer, R A

2011-10-01

The sulphated polysaccharide from the widespread Tridax procumbens plant was studied for the anticoagulant, antiherpetic and antibacterial activity. The anticoagulant activity was determined by the activated partial thromboplastin time assay. The sulphated polysaccharide from T. procumbens represented potent anticoagulant reaching the efficacy to heparin and chondroitin sulphate. Moreover, the sulphated polysaccharide extracted from T. procumbens was found non-toxic on Vero cell lines up to the concentration of 200 μg/ml. Sulphated polysaccharide exhibited detectable antiviral effect towards HSV-1 with IC(50) value 100-150 μg/ml. Furthermore, sulphated polysaccharide from T. procumbens was highly inhibitory against the bacterial strains Vibrio alginolyticus and Vibrio harveyi isolated from oil sardine.

Posttraumatic gastric wall hematoma in a patient under anticoagulant therapy. Case report and literature review.

PubMed

Mânzat Saplacan, Roberta Maria; Catinean, Adrian; Manole, Simona; Valean, Simona Doina; Chira, Romeo Ioan; Mircea, Petru Adrian

2011-06-01

We report the clinical observation of a 58-year old patient who presented with upper abdominal pain and a small ecchymosis located in the umbilical area. Personal history of the patient revealed ischemic heart disease and chronic atrial fibrillation. He was under treatment with oral anticoagulants (coumarins). The clinical data and especially the imaging investigations led to a diagnosis of gastric wall hematoma, possibly occurring post-traumatically in a patient under anticoagulant treatment. A conservative therapeutic approach was adopted and ultrasound surveillance. After 6 months the gastric parietal collection manifested complete resorption, spontaneously. In relation to the case presentation, we also discuss some issues on the frequency, diagnosis and therapeutic attitude in this rare complication of anticoagulant therapy.

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

PubMed

Ašić, Adna; Marjanović, Damir; Mirat, Jure; Primorac, Dragan

2018-05-16

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.

Novel oral anticoagulants for atrial fibrillation.

PubMed

How, Choon How

2015-12-01

Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes.

Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

PubMed

Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

2009-09-01

To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

Thrombin-inhibiting nanoparticles rapidly constitute versatile and detectable anticlotting surfaces

NASA Astrophysics Data System (ADS)

Wheatley Myerson, Jacob; He, Li; Allen, John Stacy; Williams, Todd; Lanza, Gregory; Tollefsen, Douglas; Caruthers, Shelton; Wickline, Samuel

2014-09-01

Restoring an antithrombotic surface to suppress ongoing thrombosis is an appealing strategy for treatment of acute cardiovascular disorders such as erosion of atherosclerotic plaque. An antithrombotic surface would present an alternative to systemic anticoagulation with attendant risks of bleeding. We have designed thrombin-targeted nanoparticles (NPs) that bind to sites of active clotting to extinguish local thrombin activity and inhibit platelet deposition while exhibiting only transient systemic anticoagulant effects. Perfluorocarbon nanoparticles (PFC NP) were functionalized with thrombin inhibitors (either D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone or bivalirudin) by covalent attachment of more than 15 000 inhibitors to each PFC NP. Fibrinopeptide A (FPA) ELISA demonstrated that thrombin-inhibiting NPs prevented cleavage of fibrinogen by both free and clot-bound thrombin. Magnetic resonance imaging (MRI) confirmed that a layer of thrombin-inhibiting NPs prevented growth of clots in vitro. Thrombin-inhibiting NPs were administered in vivo to C57BL6 mice subjected to laser injury of the carotid artery. NPs significantly delayed thrombotic occlusion of the artery, whereas an equivalent bolus of free inhibitor was ineffective. For thrombin-inhibiting NPs, only a short-lived (˜10 min) systemic effect on bleeding time was observed, despite prolonged clot inhibition. Imaging and quantification of in vivo antithrombotic NP layers was demonstrated by MRI of the PFC NP. 19F MRI confirmed colocalization of particles with arterial thrombi, and quantitative 19F spectroscopy demonstrated specific binding and retention of thrombin-inhibiting NPs in injured arteries. The ability to rapidly form and image a new antithrombotic surface in acute vascular syndromes while minimizing risks of bleeding would permit a safer method of passivating active lesions than current systemic anticoagulant regimes.

Rhythm vs. rate control of atrial fibrillation meta-analysed by number needed to treat.

PubMed

Kumana, Cyrus R; Cheung, Bernard M Y; Cheung, Giselle T Y; Ovedal, Tori; Pederson, Bjorn; Lauder, Ian J

2005-10-01

Whenever feasible, rhythm control of atrial fibrillation (AF) was generally preferred over rate control, in the belief that it offered better symptomatic relief and quality of life, and eliminated the need for anticoagulation. However, recent trials appear to challenge these assumptions. To explore the desirability of rhythm vs. rate control of AF by systematic review of pertinent, published, randomized controlled trials (RCTs) and a meta-analysis by number needed to treat (NNT) year(-1), with respect to diverse clinically important outcomes. RCTs of outcome primarily comparing rate vs. rhythm control in patients with spontaneous AF were identified. For each outcome and assuming rhythm control to be the active treatment, relative risk reduction (RRR) and NNT year(-1) were derived for individual trials together with an NNT year(-1) for all trials combined; corresponding 95% confidence intervals (CI) were also calculated. Adverse drug reaction (ADR) and quality of life reporting were also assessed. In all, data from five suitable RCTs (entailing 5239 patients) were analysed. For hospitalization, available RRRs and NNT year(-1) values were all clinically and statistically significant. Overall, one additional patient was hospitalized for every 35 assigned to rhythm control (95% CI 27, 48). For the endpoints of death, 'ischaemic' stroke and 'non-CNS' bleeding, there was no significant difference. ADRs were significantly more common in rhythm control patients, whereas quality of life assessments revealed no difference. Thromboembolism was associated with cessation of or subtherapeutic anticoagulation, irrespective of treatment assignment. Reduced risk of hospitalization and non-inferiority for other endpoints all favour rate control, the less costly strategy. If symptoms of AF are not a problem, treatment should target optimizing rate control and more widespread and effective prophylactic anticoagulation.

Transesophageal echocardiography (TEE) in atrial fibrillation.

PubMed

Thamilarasan, M; Klein, A L

2000-11-01

Transesophageal echocardiography has given new insight into the pathogenesis of the thromboembolic sequelae of AF and expanded the available therapeutic options. Studies to date indicate that TEE-guided cardioversion is a safe and reasonable approach when the clinical situation warrants prompt restoration of sinus rhythm. Whether widespread use of this strategy offers further benefit remains to be established, although there are theoretical advantages to such an approach. The potential for earlier cardioversion using a TEE-guided approach may facilitate the achievement and maintenance of sinus rhythm. In the long term, earlier restoration of sinus rhythm prevents adverse atrial remodeling, lowers embolic risk, and may improve cardiac performance and functional status. Thromboembolic sequelae (either cardioversion-related or as a result of chronic AF) remain the most devastating complications of AF. Every attempt to minimize this risk should be pursued aggressively. Information gathered from TEE has helped to elucidate the mechanisms responsible for postcardioversion embolism and has emphasized the importance of anticoagulation during and after the restoration of sinus rhythm. TEE also has the potential to further risk stratify patients with AF. Ultimately, a subset of patients may be identified who require more intense anticoagulation (i.e., those with dense SEC or thrombus, or persistent thrombus after prolonged anticoagulation) or in whom cardioversion may be deferred entirely. Likewise, TEE also may prove to be useful in identifying patients with a low-clinical risk profile who may be treated with aspirin alone and patients in whom warfarin may be superior. The results of the ACUTE study should help to further define the role of TEE in the management of patients with AF. Additional clinical studies are needed to address some of the issues that have been raised and to allow for optimal use of TEE in this patient population.

Safety and efficacy of switching anticoagulation to aspirin three months after successful radiofrequency catheter ablation of atrial fibrillation.

PubMed

Uhm, Jae-Sun; Won, Hoyoun; Joung, Boyoung; Nam, Gi-Byoung; Choi, Kee-Joon; Lee, Moon-Hyoung; Kim, You-Ho; Pak, Hui-Nam

2014-09-01

Although current guidelines recommend continuing the same antithrombotic strategy regardless of rhythm control after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF), anticoagulation has a risk of major bleeding. We evaluated the safety of switching warfarin to aspirin in patients with successful AF ablation. Among 721 patients who underwent RFCA of AF, 608 patients (age, 57.3±10.9 years; 77.0% male, 75.5% paroxysmal AF) who had no evidence of AF recurrence at 3 months post-RFCA were included. We compared the thromboembolic and hemorrhagic events in patients for whom warfarin was switched to aspirin (ASA group; n=296) and patients who were kept on warfarin therapy (W group; n=312). There were no significant differences in CHA₂DS₂-VASc or HAS-BLED scores between the groups. In 30 patients in the ASA group and 37 patients in W group, AF recurred and warfarin was restarted or maintained during the 18.0±12.2 months of follow-up. There were no significant differences in thromboembolic (0.3% vs. 1.0%, p=0.342) and major bleeding incidences (0.7% vs. 0.6%, p=0.958) between ASA and W groups during the follow-up period. In the 259 patients with a CHA₂DS₂-VASc score≥2, there were no significant differences in thromboembolism (0.8% and 2.2%, p=0.380) or major bleeding incidences (0.8% and 1.4%, p=0.640) between ASA and W groups. Switching warfarin to aspirin 3 months after successful RFCA of AF could be as safe and efficacious as long-term anticoagulation even in patients with CHA₂DS₂-VASc score≥2. However, strict rhythm monitoring cannot be overemphasized.

Venous thromboembolism management in Northeast Melbourne: how does it compare to international guidelines and data?

PubMed

Lim, Hui Y; Chua, Chong C; Tacey, Mark; Sleeman, Matthew; Donnan, Geoffrey; Nandurkar, Harshal; Ho, Prahlad

2017-09-01

Venous thromboembolism (VTE) is a major cause of morbidity and mortality with significant heterogeneity in its management, both within our local practice and in international guidelines. To provide a holistic evaluation of 'real-world' Australian experience in the warfarin era, including how we compare to international guidelines. Retrospective evaluation of VTE from July 2011 to December 2012 at two major hospitals in Melbourne, Australia. These results were compared to recommendations in the international guidelines. A total of 752 episodes involving 742 patients was identified. Contrary to international guidelines, an unwarranted heritable thrombophilia screen was performed in 22.0% of patients, amounting to a cost of AU$29 000. The duration of anticoagulation was longer compared to international recommendations, although the overall recurrence (3.2/100 person-years) and clinically significant bleeding rates (2.4/100 person-years) were comparable to 'real-world' data. Unprovoked VTE (hazard ratio 2.06; P = 0.01) was a risk factor for recurrence, and there was no difference in recurrence between major VTE (proximal deep vein thrombosis (DVT) and/or pulmonary embolism) and isolated distal DVT (3.02 vs 3.94/100 person-years; P = 0.25). Fourteen patients were subsequently diagnosed with malignancy, and patients with recurrent VTE had increased risk of prospective cancer diagnosis (relative risk 6.68; P < 0.001). While our 'real-world' VTE experience during the warfarin era largely correlates with international guidelines, there remains heterogeneity in the management strategies, including excessive thrombophilia screening and longer duration of anticoagulation. This audit highlights the need for national VTE guidelines, as well as prospective auditing of VTE management, in the direct oral anticoagulant era for future comparison. © 2017 Royal Australasian College of Physicians.

The value of transesophageal echocardiography for embolic strokes of undetermined source

PubMed Central

Katsanos, Aristeidis H.; Bhole, Rohini; Frogoudaki, Alexandra; Giannopoulos, Sotirios; Goyal, Nitin; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Paraskevaidis, Ioannis; Pappas, Konstantinos; Parissis, John; Kyritsis, Athanassios P.; Alexandrov, Anne W.; Triantafyllou, Nikos; Malkoff, Marc D.; Voumvourakis, Konstantinos; Alexandrov, Andrei V.

2016-01-01

Objective: Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic strokes of undetermined source (ESUS). Methods: We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups. Results: We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points [interquartile range: 3–8]). TEE revealed additional findings in 52% (95% confidence interval [CI]: 40%–65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% [95% CI: 9%–28%]) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%–10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ (p = 0.315) among patients with cryptogenic stroke (6.9% [95% CI: 4.9%–9.6%]), ESUS (8.1% [95% CI: 3.4%–18.1%]), and IS (9.4% [95% CI: 7.5%–11.8%]). Conclusions: Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS. PMID:27488602

The value of transesophageal echocardiography for embolic strokes of undetermined source.

PubMed

Katsanos, Aristeidis H; Bhole, Rohini; Frogoudaki, Alexandra; Giannopoulos, Sotirios; Goyal, Nitin; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Paraskevaidis, Ioannis; Pappas, Konstantinos; Parissis, John; Kyritsis, Athanassios P; Alexandrov, Anne W; Triantafyllou, Nikos; Malkoff, Marc D; Voumvourakis, Konstantinos; Alexandrov, Andrei V; Tsivgoulis, Georgios

2016-09-06

Our aim was to evaluate the diagnostic yield of transesophageal echocardiography (TEE) in consecutive patients with ischemic stroke (IS) fulfilling the diagnostic criteria of embolic strokes of undetermined source (ESUS). We prospectively evaluated consecutive patients with acute IS satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary care stroke centers during a 12-month period. We also performed a systematic review and meta-analysis estimating the cumulative effect of TEE findings on therapeutic management for secondary stroke prevention among different IS subgroups. We identified 61 patients with ESUS who underwent investigation with TEE (mean age 44 ± 12 years, 49% men, median NIH Stroke Scale score = 5 points [interquartile range: 3-8]). TEE revealed additional findings in 52% (95% confidence interval [CI]: 40%-65%) of the study population. TEE findings changed management (initiation of anticoagulation therapy, administration of IV antibiotic therapy, and patent foramen ovale closure) in 10 (16% [95% CI: 9%-28%]) patients. The pooled rate of reported anticoagulation therapy attributed to abnormal TEE findings among 3,562 acute IS patients included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%-10.4%). In subgroup analysis, the rates of initiation of anticoagulation therapy on the basis of TEE investigation did not differ (p = 0.315) among patients with cryptogenic stroke (6.9% [95% CI: 4.9%-9.6%]), ESUS (8.1% [95% CI: 3.4%-18.1%]), and IS (9.4% [95% CI: 7.5%-11.8%]). Abnormal TEE findings may decisively affect the selection of appropriate therapeutic strategy in approximately 1 of 7 patients with ESUS. © 2016 American Academy of Neurology.

A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study.

PubMed

Latrémouille, Christian; Carpentier, Alain; Leprince, Pascal; Roussel, Jean-Christian; Cholley, Bernard; Boissier, Elodie; Epailly, Eric; Capel, Antoine; Jansen, Piet; Smadja, David M

2018-01-01

The electro-hydraulically actuated Carmat total artificial heart (C-TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance. Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival. Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi-organ failure. Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

INR goal attainment and oral anticoagulation knowledge of patients enrolled in an anticoagulation clinic in a Veterans Affairs medical center.

PubMed

Baker, Jennifer W; Pierce, Kristi L; Ryals, Casey A

2011-03-01

In January 2009, the Joint Commission implemented a National Patient Safety Goal (NPSG) for ambulatory care, NPSG 3E, intended to reduce harm associated with the use of anticoagulation therapy. The 2011 NPSG 3E encompasses 8 elements of performance, including requirements that each organization (a) provide education regarding anticoagulation therapy to staff, patients, and families and (b) evaluate its safety practices and take appropriate action to improve its practices. The Alvin C. York (ACY) outpatient anticoagulation clinic provides education to new patients and their families at the initial clinic visit, with follow-up reinforcement of education as needed throughout their care. To (a) assess the knowledge level of patients receiving warfarin therapy in an anticoagulation clinic using the validated Anticoagulation Knowledge Assessment (AKA) questionnaire and (b) examine the relationship between patient anticoagulation knowledge and anticoagulation control as measured by the international normalized ratio (INR). All ACY Veterans Affairs (VA) anticoagulation clinic patients seen during their routine visit within an 8-week recruitment period from February 2010 to April 2010 were asked to complete the AKA questionnaire. Upon voluntary consent, the questionnaire was completed by the patient either during the clinic visit or returned later by mail. Demographic and clinical data were manually extracted from the computerized patient record system and included age, gender, indication for and duration of anticoagulation therapy, goal INR range, and the 10 INR values preceding the date of consent. A passing score was defined as at least 21 correct responses on the 29-item AKA questionnaire (72.4% correct). Statistical analyses included comparisons of demographic and clinical characteristics for patients with passing versus failing scores, assessed with Pearson chi-square and Fisher's exact test, and bivariate analyses of INR control with anticoagulation knowledge, assessed with Spearman's rho correlation. INR control was defined by 3 outcome measures: number of INRs within therapeutic range, time in therapeutic range (TTR) calculated using the Rosendaal method, and standard deviation (SD) of INR values. Anticoagulation knowledge was assessed with 2 measures: total AKA score and count of correct answers to a subset of 15 AKA items deemed by the investigators to be relevant to INR control. Of 447 patients enrolled in the anticoagulation clinic, 260 consented to participate in the survey, of whom 185 patients completed the AKA instrument (n=171 [92.4%] by mail) and were successfully matched to patient record system data. 178 (96.2%) respondents were male with a mean (SD) age of 68 (10.1) years. The majority of patients were undergoing anticoagulation treatment for atrial fibrillation (n=113, 61.1%) or deep venous/pulmonary thromboembolism (n=48, 25.9%). The majority of patients had been treated with warfarin for at least 1 year (n=162, 87.6%). Most patients had goal INR ranges of 2.0 to 3.0 (n=166, 89.7%). Of the 185 patients who completed the questionnaire, 137 (74.1%) achieved a passing score. The mean (SD) AKA questionnaire score was 78.1% (12.1%). There were 8 questions that were answered correctly by less than 70% of patients and identified as potential deficiencies in patient education. For the 167 patients who had been on warfarin therapy for at least 6 months and had 10 previous INR values, there was no significant Spearman's rho correlation between total number of correct questionnaire responses and INR control, defined as the count of the 10 previous INR values within goal range (rho =-0.022, P=0.776), TTR (rho=0.015, P=0.848), and SD (rho=0.047, P=0.550). There was also no significant relationship between number of correct INR-relevant responses and INR control by any of the 3 outcome measures (count in range rho=0.033, P=0.676; TTR rho=0.067, P=0.388; and SD rho=-0.029, P=0.708). Although 74.1% of patients on long-term warfarin therapy achieved a passing score of at least 21 correct answers on the 29-question AKA instrument, there was no significant relationship between patient warfarin knowledge and INR control. Areas for improvement in patient education have been identified and procedures for educational modification are currently in development. Copyright © 2011, Academy of Managed Care Pharmacy. All rights reserved.

Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-04-22

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

Point-of-care coagulation monitoring: first clinical experience using a paper-based lateral flow diagnostic device.

PubMed

Hegener, Michael A; Li, Hua; Han, Daewoo; Steckl, Andrew J; Pauletti, Giovanni M

2017-09-01

Vitamin K antagonists such as warfarin are the most widely used class of oral anticoagulants. Due to a narrow therapeutic window, patients on warfarin require regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is available, but cost makes this monitoring method beyond reach for many. The main objective of this research was to assess the clinical utility of a low-cost, paper-based lateral flow POC diagnostic device developed for anticoagulation monitoring without the need for a separate electronic reader. Custom-fabricated lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic backing card were assembled in a plastic cassette. Healthy volunteers and patients on warfarin therapy were recruited for this prospective study. For each participant, a whole blood sample was collected via fingerstick to determine: (1) international normalized ratio (INR) using the CoaguChek® XS coagulometer, (2) hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the experimental LFA device after 240 s using digital image analysis. RBC travel distance measured on the LFA device using blood samples obtained from warfarin patients positively correlated with increasing INR value and the LFA device had the capability to statistically distinguish between healthy volunteer INR values and those for patients groups with INR ≥ 2.6. From these data, it is predicted that this low-cost, paper-based LFA device can have clinical utility for identifying anticoagulated patients taking vitamin K antagonists who are outside of the desired therapeutic efficacy window.

Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-01-01

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

Post traumatic inferior vena cava thrombosis: A case report and review of literature.

PubMed

Chakroun, Amine; Nakhli, Mohamed Said; Kahloul, Mohamed; Harrathi, Mohamed Amine; Naija, Walid

2017-01-01

Post traumatic inferior vena cava (IVC) thrombosis is a rare and not well described entity with nonspecific clinical presentation. It remains a therapeutic challenge in traumatic context because of haemorrhagic risk due to anticoagulation. We report a case of IVC thrombosis in an 18 year-old man who presented with liver injury following a traffic crash. The thrombosis was incidentally diagnosed on admission by computed tomography. The patient was managed conservatively without anticoagulation initially considering the increasing haemorrhagic risk. IVC filter placing was not possible because of the unusual localization of the thrombus. Unfractionated heparin was started on the third day after CT scan control showing stability of hepatic lesions with occurrence of a pulmonary embolism. The final outcome was good. The management of post traumatic IVC thrombosis is not well described. Medical approach consists in conservative management with anticoagulation which requires the absence of active bleeding lesions. Surgical treatment is commonly based on thrombectomy under extracorporeal circulation. Interventional vascular techniques have become an important alternative approach for the treatment of many vessel lesions. Their main advantages are the relative ease and speed with which they can be performed. Post traumatic IVC thrombosis is a rare condition. Its management is not well defined. Early anticoagulation should be discussed on a case-by-case basis. Other alternatives such IVC filter or surgical thrombectomy may be used when the bleeding risk is increased. The most serious risk is pulmonary embolism. Outcome can be favorable even with non surgical approaches. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants.

PubMed

Weitz, Jeffrey I; Pollack, Charles V

2015-11-25

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

Pacemaker diagnostics in atrial fibrillation: limited usefulness for therapy initiation in a pacemaker practice.

PubMed

Yedlapati, Neeraja; Fisher, John D

2014-09-01

We aimed to determine the practical value of pacemaker diagnostics for atrial fibrillation (AF) in an unselected general pacemaker practice, specifically workflow and initiation of anticoagulation or antiarrhythmic drug (AAD) therapy. We prospectively followed consecutive pacemaker interrogations over a period of 1 year to identify patients with AF (burden from 1% to 99%). We contacted referring physicians with AF details, and then determined whether the information resulted in therapeutic changes. Of the 1,100 pacemakers interrogated, 728 were dual chamber (DDDs) with AF diagnostic capability. AF was recorded in 73 (10%) but seven had limited information, leaving 66 patients; of these, 42 (63%) patients were already anticoagulated and in five (7%) patients, anticoagulation had been stopped because of complications. Initial diagnosis of AF was made by the pacemaker in 17 patients (26% of 66; 2% of 728); four (6% of 66) patients were newly initiated on anticoagulation. Of the 66 patients, 17 patients were already on AADs; 49 (74%) had satisfactory rate control or had other issues; only two (3% of 66; 0.3% of 728) received new AADs. Of 728 patients with DDD pacemakers, only 17 were newly discovered to have AF, and six (0.8%) had changes in medications based on the pacemaker data. Adding pacemaker-derived data to existing clinical information had little therapeutic impact, due to a combination of cumbersome workflow, and because AF was usually known to practitioners. Developments in automated monitoring systems may provide more accessible and therapeutically useful information. ©2014 Wiley Periodicals, Inc.