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Sample records for prestroke oral anticoagulation

  1. 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

  2. Direct Oral Anticoagulants: Monitoring Anticoagulant Effect.

    PubMed

    Konkle, Barbara A

    2016-10-01

    In some clinical settings laboratory measurement of direct oral anticoagulants effect is helpful in guiding medical care, such as life-threatening bleeding, need for emergency surgery, renal impairment, severe hepatic failure, extremes of body weight, or in patients with bleeding or thrombosis on therapy. This article reviews approaches to laboratory testing to assess the anticoagulant effect of these drugs. Because of the wide variation in levels measured in patients on therapy and minimal clinical data from dose adjustment, dose adjustment based on levels is not currently advised. In addition, these drugs interfere with many clot-based laboratory tests and caution is advised in interpreting these tests in patients on direct oral anticoagulants. PMID:27637303

  3. [Direct oral anticoagulants in cardiology].

    PubMed

    Kiss, Róbert Gábor

    2016-09-01

    Antithrombotic drug therapy is a main cornerstone - sometimes a fairly uneven cornerstone - of today's clinical practice. Patients treated with antithrombotic drugs appear sometimes unawaited at those of our colleagues, who are not necessarily experts of this narrow field. Furthermore, new and newer molecules of antiplatelet and anticoagulant medicines have come into practice, frequently in combination. This dramatic development has been important to patients; pharmacological - and recently nonpharmacological - antithrombotic treatment has paved the way to improve current modalities in cardiology. Combining elements of the "old four" (heparin, coumadin, aspirin, clopidogrel) have been the basis of any improvement for a long time. Nowadays, there has been an involvement of new drugs, direct oral anticoagulants into practice. It is time now to catch up in using new anticoagulants, regardless of our current speciality in medicine. Orv. Hetil., 2016, 157(38), 1507-1510. PMID:27640616

  4. Rationale for Development of New Oral Anticoagulants.

    PubMed

    Akin, Muharrem; Widder, Julian; Akin, Ibrahim; Brehm, Michael; Schäfer, Andreas

    2015-01-01

    The development of new or direct oral anticoagulants was triggered by the disadvantages of classic oral anticoagulation, which was isolated in Link's laboratory in 1940. Some of these limitations are the individual variation in response to these drugs, drug interaction and the need for regular laboratory monitoring. With increasing comorbidity and life expectancy in populations these limitations led to interruption of treatment or even underuse of treatment in light of potential side effects. With the introduction of novel oral anticoagulants some of these drawbacks are targeted whereas even these drugs also have some limitations and should be given with cautions and not to all patients having an indication for anticoagulation.

  5. [Direct oral anticoagulant associated bleeding].

    PubMed

    Godier, A; Martin, A-C; Rosencher, N; Susen, S

    2016-07-01

    Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements. PMID:27297642

  6. [Direct oral anticoagulant associated bleeding].

    PubMed

    Godier, A; Martin, A-C; Rosencher, N; Susen, S

    2016-07-01

    Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements.

  7. Direct oral anticoagulants and venous thromboembolism.

    PubMed

    Franchini, Massimo; Mannucci, Pier Mannuccio

    2016-09-01

    Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE. PMID:27581829

  8. [New oral anticoagulants (NOAC) in nephrology].

    PubMed

    Bellasi, Antonio; Di Lullo, Luca; Melfa, Gianvincenzo; Minoretti, Claudio; Ratti, Carlo; Campana, Carlo; Volpi, Maurizio; Mangano, Stefano; Di Iorio, Biagio; Cozzolino, Mario

    2016-01-01

    The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice. However, while available data suggest that NOAC/DOAC use is safe, dosage should be adjusted based on renal or liver function. It should be acknowledged that commonly available blood tests [Prothrombin Time (PT) and partial thromboplastin time (PTT)] are not indicated to monitor the anticoagulant activity of these compounds. With the exception of dabigatran, we currently lack of an antidote to reverse the anticoagulant effect of NOAC/DOAC. We herein review available evidence on NOAC/DOAC pharmacokinetic, risk factors for bleeding, interventions to reverse the anticoagulant activity in case of hemorrhages or need of urgent surgery and/or NOAC/DOAC overdose or side effects. PMID:27545637

  9. New Oral Anticoagulants for Atrial Fibrillation

    PubMed Central

    Shafeeq, Hira; Tran, Tran H.

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in the U.S. Anticoagulation is recommended for stroke prevention in AF patients with intermediate-to-high stroke risk (i.e., patients with a CHADS2 score of 1 or greater). Warfarin was previously the only option for oral anticoagulation in these patients, but three new oral anticoagulants have become available as alternatives for warfarin in patients with nonvalvular AF. The advantages of the newer agents include a rapid onset, predictable pharmacokinetics, and no need for routine anticoagulation monitoring. Dabigatran (Pradaxa) and apixaban (Eliquis) have demonstrated improved efficacy compared with warfarin. Rivaroxaban (Xarelto) was non-inferior to warfarin for stroke prevention in AF. Apixaban demonstrated a reduced incidence of major bleeding compared with warfarin and a reduction in all-cause mortality. Limitations to the use of the new oral anticoagulants include the lack of a reversal agent; an inability to use the therapies in specific patient populations (such as those with severe renal or hepatic impairment); limited experience with drug–drug and drug–disease interactions; and a lack of available coagulation tests to quantify their effects. Although the newer agents have higher acquisition costs, the benefits of cost savings may be derived from the potential for decreasing the incidence of hemorrhagic stroke and intracranial bleeding and reducing the need for anticoagulation monitoring. Benefits and risks should be carefully weighed before these agents are prescribed for patients presenting with new-onset AF. PMID:24672216

  10. Monitoring anticoagulant therapy with new oral agents.

    PubMed

    Ramos-Esquivel, Allan

    2015-12-26

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  11. Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

    PubMed Central

    Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils

    2016-01-01

    Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226

  12. Reversal Agents for the Direct Oral Anticoagulants.

    PubMed

    Ansell, Jack E

    2016-10-01

    The vitamin K antagonists (VKAs) are associated with a significant rate of major and fatal bleeding complications. The new direct oral anticoagulants (DOACs), even though having a better bleeding profile than the VKAs, are still associated with serious bleeding. The anticoagulation induced by the VKAs can be reversed with both vitamin K and prothrombin complex concentrates, whereas the DOACs were developed without specific reversal agents. Although there is controversy around the necessity of a reversal agent, most clinicians agree that having a reversal agent for the DOACs would be beneficial. Three reversal agents are currently in development. PMID:27637309

  13. [Therapeutic equivalence of the new oral anticoagulants].

    PubMed

    Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L

    2015-10-01

    In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. PMID:26146035

  14. [New oral anticoagulants in atrial fibrillation].

    PubMed

    Veltkamp, R; Hacke, W

    2011-02-01

    Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2 × 150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC. PMID:21286676

  15. Direct oral anticoagulants: integration into clinical practice

    PubMed Central

    Cowell, Richard P W

    2014-01-01

    The introduction of direct oral anticoagulants (OACs) for the treatment and prevention of thromboembolic disease represents a shift from the traditional vitamin K antagonist-based therapies, which have been the mainstay of treatment for almost 60 years. A challenge for hospital formularies will be to manage the use of direct OACs from hospital to outpatient settings. Three direct OACs—apixaban, dabigatran and rivaroxaban—are widely approved across different indications, with rivaroxaban approved across the widest breadth of indications. A fourth direct OAC, edoxaban, has also completed phase III trials. Implementation of these agents by physicians will require an understanding of the efficacy and safety profile of these drugs, as well as an awareness of renal function, comedication use, patient adherence and compliance. Optimal implementation of direct OACs in the hospital setting will provide improved patient outcomes when compared with traditional anticoagulants and will simplify the treatment and prevention of thromboembolic diseases. PMID:25012514

  16. Self management of oral anticoagulation: randomised trial

    PubMed Central

    Fitzmaurice, D A; Murray, E T; McCahon, D; Holder, R; Raftery, J P; Hussain, S; Sandhar, H; Hobbs, F D R

    2005-01-01

    Objective To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. Design Multicentre open randomised controlled trial. Setting Midlands region of the UK. Participants 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. Intervention Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. Main outcome measure Percentage of time spent within the therapeutic range of international normalised ratio. Results No significant differences were found in percentage of time in the therapeutic range between self managment and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (χ2(df = 1) = 0.02, P = 0.89). Conclusion With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375. PMID:16216821

  17. Avoiding Medication Errors: Reducing Harm in Residents Using Oral Anticoagulants.

    PubMed

    Grissinger, Matthew; Gaunt, Michael J; Rich, Darryl S

    2016-01-01

    Medication errors involving oral anticoagulants have led to serious adverse events, including hemorrhage, treatment failures leading to thromboembolic events, and death. This article will highlight medication errors that may arise during the use of oral anticoagulants and provide risk-reduction strategies to address the potential for error and patient harm. PMID:27250070

  18. Sudden sensorineural hearing loss during oral anticoagulant therapy.

    PubMed

    Mierzwa, Kathleen; Schneider, Gerlind; Müller, Andreas

    2004-11-01

    This study investigated the role of sudden sensorineural hearing loss (SSNHL) as a symptom in oral anticoagulant therapy with vitamin K antagonists (Phenprocoumon; Marcumar, Falithrom). Vascular compromise of the cochlea due to thrombosis, embolus, reduced blood flow or vasospasm is one of the four possible pathways that can lead to SSNHL. Oral anticoagulant therapy should prevent thrombosis; if it does not the question arises as to whether the anticoagulation is working, or the wrong hypothesis of vascular compromise has been made. Patients with SSNHL during oral anticoagulant therapy who were admitted to the ENT Department of the University Hospital in Jena from 1998 to 2001 were included. The pure-tone audiograms and the prothrombin time (PT) values before and after the event of the SSNHL were evaluated. The study found 10 patients with SSNHL during oral anticoagulant therapy. Although the audiograms showed some improvement in the majority of cases, three cases showed almost no improvement in hearing. On admission, half of the patients showed a PT-value higher than 30 per cent and in nine cases a PT-value >30 per cent could be demonstrated at least once during testing. It was not possible to demonstrate a relationship between the SSNHL and oral anticoagulation. Vascular compromise cannot be excluded as a cause for sudden hearing loss in patients undergoing oral anticoagulant therapy. It is possible that oral anticoagulants influence the viscosity of the plasma leading to interference with the microcirculation in the inner ear. Further research into this area is currently being conducted.

  19. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.

    PubMed Central

    Vigano D'Angelo, S; Comp, P C; Esmon, C T; D'Angelo, A

    1986-01-01

    Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals. PMID:3511097

  20. Interpretation of coagulation test results under direct oral anticoagulants.

    PubMed

    Mani, H

    2014-06-01

    Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.

  1. [Antidotes to novel direct oral anticoagulants].

    PubMed

    Khorev, N G; Momot, A P; Kon'kova, V O

    2016-01-01

    During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations. PMID:27626268

  2. [New oral anticoagulants - influence on coagulation tests].

    PubMed

    Simeon, L; Nagler, M; Wuillemin, W A

    2014-01-01

    The new oral anticoagulants (NOACs) represent alternative antithrombotic agents for prophylaxis and therapy of thromboembolic diseases. They act either by inhibition of the clotting factor Xa or IIa (thrombin). As a consequence, they influence several coagulation assays (for example prothrombin time, activated partial thromboplastin time). Because of the short half-life of these new agents, these changes show great variations in the course of 24 hours. Furthermore, there are significant differences of laboratory results depending on the used reagents. We explain the influence of apixaban, rivaroxaban (factor Xa inhibitors) and dabigatran (thrombin inhibitor) on the most commonly used coagulation assays. Besides we show that this influence depends on the way of action of the drug as well as on the principle of the coagulation assay. Being aware of this relationships helps to interpret the results of coagulation assays under influence of NOACs correctly.

  3. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection. PMID:23957907

  4. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.

  5. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning.

    PubMed

    Myers, B; Neal, R; Myers, O; Ruparelia, M

    2016-03-01

    Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants), as the name suggests, are oral anticoagulants with a direct inhibitory action either against factor X or factor II (thrombin). Pregnant women were excluded from participating in all the large trials of the DOACs and they are considered contra-indicated in pregnancy and breast feeding. We present a case of inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks' gestation. The management of her pregnancy and delivery is described, and the previous published case reports are reviewed with a discussion about the use of DOACs in woman of childbearing age. PMID:27512489

  6. Peri-procedural management of patients taking oral anticoagulants.

    PubMed

    Daniels, Paul R

    2015-07-14

    The use of oral anticoagulants is becoming increasingly common. For many years warfarin was the main oral anticoagulant available, but therapeutic options have expanded with the introduction of oral direct thrombin (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Management of patients taking any oral anticoagulant in the peri-procedural period poses a challenge to medical and surgical providers because of the competing risks of thrombosis and hemorrhage. Bridging therapy has been used to minimize time without anticoagulation when warfarin is interrupted for invasive procedures, but validated strategies based on high quality data are lacking. Existing data suggest that the use of bridging therapy may increase the risk of bleeding for some patients without reducing the risk of thrombosis. Clinical trials are currently under way to answer these questions. Because the half lives and time to anticoagulant activity of newer oral anticoagulants are shorter than for warfarin, bridging therapy is not thought to be necessary with these agents. Peri-procedural management of patients taking these agents is complicated by the lack of demonstrated reversal agents in emergency situations, although specific antidotes are being developed and tested. Existing guidelines for peri-procedural management of patients on oral anticoagulants highlight the importance of individualized patient decision making and suggest strategies to minimize complications. From a patient's perspective, given the uncertainties surrounding optimal management, explicit discussions regarding risks and benefits of treatment options and demonstration of effective communication among medical and surgical providers are essential.

  7. Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

    PubMed Central

    Anakwue, RC; Ocheni, S; Madu, AJ

    2014-01-01

    Background: Anticoagulation is an essential lifesaving management practice indicated for arterial, venous and intracardiac thromboembolism. Aim: This study was undertaken to examine the utilization of anticoagulation services in University of Nigeria Teaching Hospital, Enugu (UNTH) Nigeria. Materials and Methods: This retrospective study involved assessing data from folders of subjects on anticoagulation and monitoring in UNTH, Enugu. Patients’ profile, risk factors, diagnosis, indication for oral anticoagulation, anticoagulant used; target, monitoring, outcome and complications of anticoagulation were recorded. Results: A total of 26 patients over a period of 5 years were on anticoagulation and laboratory monitoring done in UNTH. The mean age of the patients was 53.4 years and more females than males were on anticoagulation and monitoring (F14:M12). The most common indications for anticoagulation include deep venous thrombosis/pulmonary embolism, congestive heart failure with atrial fibrillation and mitral valve disease with atrial fibrillation. Desired clinical outcome was achieved in eight patients 8/26 (30.8%). Minor bleeding was the only complication reported in three patients 3/26 (11.5%). Conclusion: The absence of diagnostic tools and anticoagulation monitoring clinics and the apprehension of adverse effects have combined to make this lifesaving treatment inaccessible to many patients in Nigeria. PMID:25364603

  8. Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.

    PubMed

    Perram, Jacinta; Joseph, Joanne; Holloway, Cameron

    2015-01-01

    Compatibility of novel oral anticoagulants in patients with HIV taking combined antiretroviral therapy has not been established, with no published reports of successful concurrent use. We present a case where chronic anticoagulation was indicated in a patient with treated HIV and non-valvular atrial fibrillation who refused warfarin therapy. The patient tolerated the combination, with dabigatran blood levels within the expected range at a standard dosing regimen, without evidence of bleeding or other adverse outcomes. While further research is needed to establish the role of novel oral anticoagulants in patients taking antiretrovirals, this case suggests that dabigatran may be a viable option for selected patients.

  9. New oral anticoagulants: are coagulation units still required?

    PubMed Central

    2014-01-01

    Chronic antithrombotic therapy involves the use of anticoagulants, antiplatelets given either as monotherapy or in combination for the prevention of thrombotic complications. The most feared and sometimes fatal complication with this therapy is bleeding. It should be considered a “golden rule” that a drug or combination of drugs that maximizes efficiency (decreased thromboembolic risk) will probably be less safe (increased risk of bleeding), and this holds true either for single therapy or during combined therapy. The chances of bleeding indicated by risk tables can be useful but show only a snapshot, and the biological, social, environmental, and drug changes and therapeutic adherence also determine changes in the risk of thrombosis and bleeding. Bleeding is an eventuality that occurs in places of “locus minoris resistentiae,” and the results of careful phase 3 studies thus cannot be completely predictive of outcomes when a medication is introduced on the pharmaceutical market. With the use of warfarin, the International Normalized Ratio (INR) that has been established to indicate adequately balanced therapy is between 2.0 and 3.0. With the new oral anticoagulants, the pharmaceutical companies emphasize that it is not necessary to monitor anticoagulant effects. In studies with different doses of new oral anticoagulants, however, incidence of clinically significant bleeding complications have been directly related to the doses. Therefore, therapeutic excesses can condition bleeding risk and therapeutic limitation can increase thrombotic risk, especially when short-acting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants, setting levels of safety and effectiveness through periodic dosage and monitoring of their anticoagulant effects. Therefore, we still recommend the use of anticoagulation units for monitoring during treatment with the new oral anticoagulants

  10. New antiplatelet drugs and new oral anticoagulants.

    PubMed

    Koenig-Oberhuber, V; Filipovic, M

    2016-09-01

    In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents. PMID:27566810

  11. [Genetic predisposition to bleeding during oral anticoagulants treatment].

    PubMed

    Montes Díaz, R; Nantes, O; Molina, E; Zozaya, J; Hermida, J

    2008-01-01

    The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagic risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion.

  12. The management of dental patients taking new generation oral anticoagulants.

    PubMed

    Scott, Alun; Gibson, John; Crighton, Alexander

    2014-11-01

    Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. PMID:25668377

  13. Development and Validation of an Oral Anticoagulation Knowledge Tool (AKT)

    PubMed Central

    Obamiro, Kehinde O.; Chalmers, Leanne; Bereznicki, Luke R. E.

    2016-01-01

    Background Assessing and improving patients’ anticoagulation knowledge can lead to better treatment outcomes. While validated knowledge instruments exist for use in people taking warfarin, these tools are not necessarily applicable to patients taking direct-acting oral anticoagulants. Objective To develop and validate an oral anticoagulation knowledge instrument that is applicable to all oral anticoagulant medications. Methods Ten anticoagulation experts participated in the development of the Anticoagulation Knowledge Tool to ensure content validity. The knowledge instrument was administered to three groups of participants comprising of 44 pharmacists, 50 patients and 50 members of the general public. A subgroup of participants in the patient and pharmacist group were retested approximately 2–3 months after the initial testing. Statistical tests were conducted to determine the validity and reliability of the scale, and item analysis was used to determine the performance of individual questions. Results The 28-item instrument developed had a scale content validity index of 0.92, supporting content validity. The pharmacist group’s mean score was significantly higher than that of the patient group, and the patient group scored significantly higher than the general public group (94% vs 62% vs 20%, respectively; p<0.001), supporting construct validity. Internal consistency reliability was acceptable with a Cronbach’s α value of > 0.7 across the three groups, and the test–retest reliability was confirmed with a Pearson’s correlation coefficient of 0.72 and 0.78 for the pharmacist and patient groups, respectively. Conclusion The Anticoagulation Knowledge Tool is a valid and reliable instrument that can be used in routine clinical practice to assess patients’ anticoagulation knowledge. PMID:27351746

  14. Quick reference guide to the new oral anticoagulants.

    PubMed

    Hurst, Katherine; Lee, Regent; Handa, Ashok

    2016-06-01

    After the commissioning of new oral anticoagulants for the treatment and prevention of thrombosis, these medications are now widely used within clinical settings. Increasing numbers of patients present to the health services on anticoagulant medications, and it is therefore imperative for surgeons to be aware of the new therapeutic treatments available and how patients will benefit from such interventions. This review highlights the most pertinent learning points for surgeons regarding the indications, pharmacokinetics, and perioperative management of these new oral medications, as a quick reference guide. PMID:27113315

  15. [Improvements in oral anticoagulant therapy for atrial fibrillation].

    PubMed

    Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José

    2013-12-01

    For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

  16. Novel oral anticoagulants in development: Dabigatran, Rivaroxaban, and Apixaban.

    PubMed

    Sattari, Maryam; Lowenthal, David T

    2011-07-01

    Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists, such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule factor Xa inhibitors and thrombin inhibitors. With their potentially consistent and predictable clinical profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management. PMID:20535013

  17. New oral anticoagulants for patients with nonvalvular atrial fibrillation.

    PubMed

    Holden, Amber; Azimi, Nassir; Forest, Christopher P

    2015-11-01

    Four new oral anticoagulants have been approved for reducing stroke risk in patients with nonvalvular atrial fibrillation. Compared with warfarin, these agents offer a more predictable dose response with fewer food and drug interactions and no regular blood monitoring, although some of the drugs have an increased risk of major gastrointestinal bleeding. This article reviews the new drugs.

  18. Novel oral anticoagulants in secondary prevention of stroke.

    PubMed

    Diener, H C; Easton, J D; Hankey, G J; Hart, R G

    2013-06-01

    In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making. PMID:23953901

  19. Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants.

    PubMed

    Hillis, Christopher M; Crowther, Mark A

    2015-06-01

    The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patient's social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

  20. How we treat bleeding associated with direct oral anticoagulants

    PubMed Central

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M.; Franchini, Massimo

    2016-01-01

    Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433

  1. How we treat bleeding associated with direct oral anticoagulants.

    PubMed

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M; Franchini, Massimo

    2016-09-01

    Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433

  2. [Why, when and how to monitor new oral anticoagulants].

    PubMed

    Tamigniau, Anne; Douxfils, Jonathan; Nicolas, Jean-Baptiste; Devalet, Bérangère; Larock, Anne-Sophie; Spinewine, Anne; Dincq, Anne-Sophie; Lessire, Sarah; Gourdin, Maximilien; Watelet, Jean-Baptiste; Mathieux, Valerie; Chatelain, Christian; Dogné, Jean-Michel; Chatelain, Bernard; Mullier, François

    2014-02-01

    Several direct oral anticoagulants (DOACs) are now widely used in the prevention and treatment of thromboembolic events. Unlike vitamin K antagonists, DOACs exhibit predictable pharmacokinetics and pharmacodynamics. DOACs are to be administered at fixed doses without routine coagulation monitoring. However, in some patient populations or specific clinical circumstances, measurement of drug exposure may be useful, such as in suspected overdose, in patients with a haemorrhagic or thromboembolic event during treatment with an anticoagulant, in those with acute renal failure, or in patients who require urgent surgery. This article provides practical guidance on laboratory testing of DOACs in routine practice and summarizes the influence of DOACs on commonly used coagulation assays. PMID:24624625

  3. Use of Direct Oral Anticoagulants in Special Populations.

    PubMed

    Li, Ang; Lopes, Renato D; Garcia, David A

    2016-10-01

    Direct oral anticoagulants (DOACs) have been approved for the treatment of venous thromboembolism and atrial fibrillation based on randomized controlled trials (RCTs) of direct comparisons with vitamin K antagonists. Despite having more than 100,000 patients enrolled, safety and efficacy are debated in selected populations. Although DOACs are reviewed as a class of anticoagulant, pharmacokinetic differences exist such that different medications may be beneficial in distinct clinical settings. Synthesizing available evidence based on phase III RCTs, post hoc subgroup analyses, and pooled metaanalyses, this review provides an overview of DOACs and scrutinizes individual differences in their applications for the special populations. PMID:27637307

  4. Application of the theory of planned behavior to oral anticoagulant therapy.

    PubMed

    Burns, Sharita

    2009-03-01

    Anticoagulation control is imperative for individuals who are prescribed long-term oral anticoagulation therapy. Therapeutic international normalized ratios decrease the risk of the thromboembolic complications that are associated with oral anticoagulation therapy. Individuals on oral anticoagulation therapy are often asked to make lifestyle modifications that can become barriers to medication adherence. The application of the theory of planned behavior to oral anticoagulation therapy can be used to assist advanced practice nurses in assessing individuals for the perceived barriers or obstacles that might interfere with the behavioral changes necessary to successfully comply with the recommended treatment plan. PMID:19298315

  5. The role of anticoagulation clinics in the era of new oral anticoagulants.

    PubMed

    Testa, Sophie; Paoletti, Oriana; Zimmermann, Anke; Bassi, Laura; Zambelli, Silvia; Cancellieri, Emilia

    2012-01-01

    Anticoagulation Clinics (ACs) are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs), but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs) have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.

  6. [The role of new oral anticoagulants in cerebrovascular diseases].

    PubMed

    Orosz, Péter

    2015-12-01

    Cardioembolisation is responsible for 20 percent of ischaemic stroke cases, which most commonly derives from non-valvular atrial fibrillation. Although warfarin is highly effective in primary and secondary stroke prevention, its use is limited by the high risk of haemorrhagic complications and a narrow therapeutic range that needs regular monitoring of INR. These limitations explained the strong need for developing new oral anticoagulants. The so-called 'new oral anticoagulants' are trying to find new targets for modifying the coagulation cascade. Apixaban, edoxaban and rivaroxaban are direct factor Xa inhibitors, while dabigatran works as a direct thrombin inhibitor. Recent phase-III clinical trials proved their effectiveness in stroke prevention and risk reducing of haemorrhagic events as well, so they can already be found as recommended drugs in new guidelines of European and American societies of cardiology and stroke. The use of new oral anticoagulants instead of warfarin in patients with atrial fibrillation or as a secondary prevention after cardioembolic stroke has to be considered. PMID:26727722

  7. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

    PubMed

    Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R

    2008-06-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major

  8. Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

    PubMed Central

    Hu, Tiffany Y; Vaidya, Vaibhav R; Asirvatham, Samuel J

    2016-01-01

    Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials. PMID:26937198

  9. Drug Interactions of Direct-Acting Oral Anticoagulants.

    PubMed

    Fitzgerald, John Leonard; Howes, Laurence Guy

    2016-09-01

    In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems. PMID:27435452

  10. The target-specific oral anticoagulants: practical considerations.

    PubMed

    Garcia, David A

    2014-12-01

    More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.

  11. Perioperative management of patients receiving new oral anticoagulants: an international survey.

    PubMed

    Faraoni, David; Samama, Charles Marc; Ranucci, Marco; Dietrich, Wulf; Levy, Jerrold H

    2014-09-01

    New oral anticoagulants (NOACs) are increasingly replacing standard anticoagulants. These new drugs have been recently introduced in clinical practice, and specific knowledge regarding preoperative interruption, anticoagulation assessment, and reversal therapies is needed. In this article, 3 main areas related to perioperative NOACs management are discussed: (1) physicians' knowledge, (2) current practices, and (3) perspectives to improve management of patients treated with NOACs.

  12. The new oral anticoagulants: a challenge for hospital formularies.

    PubMed

    Merli, Geno J

    2012-08-01

    Introduction Over the past 60 years, clinicians have used vitamin K antagonists, primarily warfarin, as the sole oral anticoagulants for managing a variety of thrombotic disorders. Warfarin, which requires frequent monitoring, has a variable dose response, a narrow therapeutic index, and numerous drug and dietary interactions. However, intravenous and subcutaneous agents, such as unfractionated heparin, low-molecular-weight heparin, direct thrombin inhibitors, and pentasaccharide, have been introduced over the past 30 years for managing thromboembolic disorders. Recently, 5 new oral anticoagulants, dabigatran, rivaroxaban, apixaban, endoxaban, and betrixaban, have been introduced into clinical trials. Apixaban, rivaroxaban, endoxaban, and betrixaban are specific direct inhibitors of factor Xa, while dabigatran inhibits factor IIa. These drugs have a pharmacological profile that does not require monitoring in order to adjust therapy, which is the mainstay of warfarin management. In addition, these new medications have not shown any major issues regarding food interactions; rather, they demonstrate the potential for limited drug-drug interactions due to their limited metabolism through the cytochrome P450 system. This unique pharmacokinetic profile may provide clinicians with a new era of managing thromboembolic disorders. Two of these agents, dabigatran and rivaroxaban, have been approved by the US Food and Drug Administration (FDA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF); in addition, rivaroxaban can be used in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty during the acute and extended periods of risk. However, the challenge for hospital formularies will be the appropriate use and management of these new medications as they become integrated into outpatient care. In order to better understand the issues that pharmacy and therapeutics committees will encounter, a review of the 2 FDA

  13. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.

  14. A rare cause of recurrent cerebral emboli despite oral anticoagulation

    PubMed Central

    Dzialowski, Imanuel; Wolz, Martin; Meinhardt, Matthias; Waldow, Thomas

    2014-01-01

    We report on a patient with a history of colon carcinoma and clinical presentation of recurrent cardiac emboli despite oral anticoagulation for atrial fibrillation. On delayed transoesophageal echocardiography, finally a left atrial myxoma was suspected. Surgery, however, revealed a left atrial metastatic tumour with histopathological features of a colon adenocarcinoma. Metastases of colorectal adenocarcinoma invading cardiac structures are rare. Isolated literature reports describe metastatic masses detected in the right atrium reflecting natural haematogenous spreading of cancer, but none in the left heart. PMID:25246459

  15. Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation.

    PubMed

    Plitt, Anna; Ruff, Christian T; Giugliano, Robert P

    2016-10-01

    For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described. PMID:27637305

  16. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain. PMID:24889748

  17. Noncompaction and embolic myocardial infarction: the importance of oral anticoagulation.

    PubMed

    Pulignano, Giovanni; Tinti, Maria Denitza; Tolone, Stefano; Musto, Carmine; De Lio, Lucia; Pino, Paolo Giuseppe; Minardi, Giovanni; Violini, Roberto; Uguccioni, Massimo

    2015-01-01

    Left ventricular noncompaction (LVNC) is characterized by left ventricular (LV) hypertrabeculations and is associated with heart failure, arrhythmias and embolism. We report the case of a 67-year-old LVNC patient, under oral anticoagulation (OAC) therapy for apical thrombosis. After she discontinued OAC, the thrombus involved almost the whole of the left ventricle; in a few months her condition worsened, requiring hospitalization, and despite heparin infusion she experienced myocardial infarction (MI), caused by embolic occlusion of the left anterior descending artery. Although infrequent as a complication of LVNC, and usually attributable to microvascular dysfunction, in this case MI seems due to coronary thromboembolism from dislodged thrombotic material in the left ventricle.

  18. Strategies for urgent reversal of target-specific oral anticoagulants.

    PubMed

    Davis, Estella M; Uhlmeyer, Erin M; Schmidt, David P; Schardt, Greg L

    2014-12-01

    The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are US Food and Drug Administration (FDA)-approved target-specific oral anticoagulants (TSOACs) that have emerged onto the market for use in some indications similar to those for warfarin; in addition, edoxaban is seeking FDA approval. Similar indications include reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for all 3 agents, for the prevention of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing hip or knee surgery for rivaroxaban and apixaban, and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. As anticoagulants, they are all associated with a risk of bleeding, and, unfortunately, there are no approved antidotes for reversal of these agents. A number of small studies in human subjects and in human/animal models exposed to TSOACs have evaluated the use of activated charcoal, hemodialysis for dabigatran, or clotting factor concentrates for their ability to neutralize the anticoagulant effects or reduce drug concentrations of TSOACs. Clotting factor concentrates that have been used include prothrombin complex concentrates and recombinant factor VII. This review examines studies and case reports evaluating these strategies for expedited or emergent reversal of TSOACs. PMID:25485923

  19. Strategies for urgent reversal of target-specific oral anticoagulants.

    PubMed

    Davis, Estella M; Uhlmeyer, Erin M; Schmidt, David P; Schardt, Greg L

    2014-12-01

    The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are US Food and Drug Administration (FDA)-approved target-specific oral anticoagulants (TSOACs) that have emerged onto the market for use in some indications similar to those for warfarin; in addition, edoxaban is seeking FDA approval. Similar indications include reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for all 3 agents, for the prevention of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing hip or knee surgery for rivaroxaban and apixaban, and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. As anticoagulants, they are all associated with a risk of bleeding, and, unfortunately, there are no approved antidotes for reversal of these agents. A number of small studies in human subjects and in human/animal models exposed to TSOACs have evaluated the use of activated charcoal, hemodialysis for dabigatran, or clotting factor concentrates for their ability to neutralize the anticoagulant effects or reduce drug concentrations of TSOACs. Clotting factor concentrates that have been used include prothrombin complex concentrates and recombinant factor VII. This review examines studies and case reports evaluating these strategies for expedited or emergent reversal of TSOACs.

  20. Evaluating the Initiation of Novel Oral Anticoagulants in Medicare Beneficiaries

    PubMed Central

    Baik, Seo Hyon; Hernandez, Inmaculada; Zhang, Yuting

    2016-01-01

    BACKGROUND As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs—dabigatran and rivaroxaban. METHODS We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did

  1. 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

  2. Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...

  3. Comparative study of two portable systems for oral anticoagulant monitoring.

    PubMed

    Vacas, Marta; Lafuente, Pedro José; Unanue, Iciar; Iriarte, José Antonio

    2004-01-01

    Portable prothrombin time (PT) monitors offer the potential for both simplifying and improving oral anticoagulation management. It is necessary to evaluate their concordance and correlation with other PT systems. Our objective was to evaluate the concordance and clinical correlation of two portable PT determination systems, ProTime (ITC) and CoaguChek S (Roche Diagnostics). In all, 20 healthy individuals and 60 anticoagulated patients stabilized over 3 months in a therapeutic International Normalized Ratio (INR) range between 2-3.5 were studied. A drop of capillary blood was obtained simultaneously from two different fingers of each patient and applied to the monitor's application zone. The mean INR of the patients' blood samples of the two monitors differed by 0.01 units (2.32+/-0.63 for Pro Time and 2.33+/-0.68 for CoaguChek). The percentage of simple concordance and the kappa index were 88.3 and 75.9%, respectively. The coefficient of correlation was 0.922. The mean difference (bias) between the monitors was 0.01. The portable PT monitors evaluated presented a high percentage of concordance in INR results.

  4. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To compare key features of the new oral anticoagulants (NOACs)—dabigatran, rivaroxaban, and apixaban—and to address questions that arise when comparing the NOACs. Sources of information PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE). Main message All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction). Conclusion The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common “what if” questions that arise in the long-term clinical follow-up and management of patients receiving NOACs. PMID:25392438

  5. Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

    ERIC Educational Resources Information Center

    Pettifor, J. M.; Benson, R.

    1975-01-01

    Reported are case histories of three infants with congenital malformations (including defective formation of the nose and hands) associated with ingestion of oral anticoagulants during the first trimester of pregnancy. (CL)

  6. Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation

    PubMed Central

    Sherwood, Matthew W.; Becker, Richard C.

    2014-01-01

    Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making. PMID:23846737

  7. Overview of the new oral anticoagulants: opportunities and challenges.

    PubMed

    Yeh, Calvin H; Hogg, Kerstin; Weitz, Jeffrey I

    2015-05-01

    The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for many indications. These agents include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. All 4 agents are licensed in the United States for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism and rivaroxaban and apixaban are approved for thromboprophylaxis after elective hip or knee arthroplasty. The NOACs are at least as effective as warfarin, but are not only more convenient to administer because they can be given in fixed doses without routine coagulation monitoring but also are safer because they are associated with less intracranial bleeding. As part of a theme series on the NOACs, this article (1) compares the pharmacological profiles of the NOACs with that of warfarin, (2) identifies the doses of the NOACs for each approved indication, (3) provides an overview of the completed phase III trials with the NOACs, (4) briefly discusses the ongoing studies with the NOACs for new indications, (5) reviews the emerging real-world data with the NOACs, and (6) highlights the potential opportunities for the NOACs and identifies the remaining challenges. PMID:25792448

  8. Balancing ischaemia and bleeding risks with novel oral anticoagulants.

    PubMed

    Baber, Usman; Mastoris, Ioannis; Mehran, Roxana

    2014-12-01

    Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention. PMID:25367652

  9. New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications.

    PubMed

    Fenger-Eriksen, C; Münster, A-M; Grove, E L

    2014-07-01

    New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa-inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents. This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.

  10. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To address common “what if” questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs). Sources of information For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings. Main message Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis. Conclusion Management of “what if” scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and

  11. Suboptimal use of non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Cağri; Kalaycioğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalcik, Macit; Yaman, Mehmet; İnci, Sinan; Altintaş, Bernas; Kalkan, Sedat; Kirma, Cevat; Biteker, Murat

    2016-01-01

    Abstract This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians’ adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study). RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression. Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3. The suboptimal use of NOACs is common because of physicians’ poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients. PMID:27583892

  12. Non-vitamin K antagonist oral anticoagulants (NOACs): a view from the laboratory.

    PubMed

    Blann, A D

    2014-01-01

    Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory. PMID:25562993

  13. 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.

  14. New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: More Choices Bring More Challenges

    PubMed Central

    Howard, Patricia A.

    2013-01-01

    For patients with atrial fibrillation, anticoagulant therapy is essential to reduce the risk of ischemic stroke that is associated with this arrhythmia. Historically, warfarin has been the preferred treatment for patients at moderate to high risk despite many potential limitations. With the development of newer oral anticoagulants, clinicians now have 3 additional options: dabigatran, rivaroxaban, and apixaban. Although these agents clearly offer some advantages over warfarin, they may not be appropriate for all patients. This article will discuss factors that should be considered when selecting among these various anticoagulants. PMID:24421491

  15. New oral anticoagulants: their role in stroke prevention in high-risk patients with atrial fibrillation.

    PubMed

    Ferns, Sunita J; Naccarelli, Gerald V

    2015-07-01

    Based on efficacy, safety, and ease of use, novel oral anticoagulants will likely replace VKAs for many if not most patients with atrial fibrillation. Novel anticoagulants have a lower rate of intracranial hemorrhage compared with vitamin K antagonists. The incidence of other life-threatening bleeds is similar if not lower. Dose adjustments need to be made based on renal function and advanced age. There is at present a need for an antidote for these new drugs.

  16. Anticoagulation

    MedlinePlus

    ... gums or nosebleeds. Oral Medications These mainly include aspirin or clopidogrel (Plavix) and warfarin (Coumadin). These medications ... will decide which one is right for you. Aspirin tends to cause fewer bleeding complications than clopidogrel ...

  17. Real Data on Effectiveness, Tolerability and Safety of New Oral Anticoagulant Agents: Focus on Dabigatran.

    PubMed

    Stabile, Eugenio; Izzo, Raffaele; Rozza, Francesco; Losi, Maria Angela; Coscioni, Enrico; Trimarco, Bruno

    2016-06-01

    Vitamin K-dependent antagonists (VKAs) are the most commonly used oral anticoagulants. Non-VKA oral anticoagulants (NOACs), directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, and edoxaban) have predictable pharmacological effects and relatively few drug and food interactions compared with VKA. Among NOACs, dabigatran has been extensively tested for stroke prevention in patients with non-valvular atrial fibrillation eligible for oral anticoagulation with VKA. Dabigatran is at least as effective as warfarin at preventing stroke with advantages of less serious bleeding except for gastrointestinal bleeding, which occurs more often than with warfarin. The findings of dabigatran use in randomized trials, post market registries and specific clinical settings are discussed in this article. PMID:27207360

  18. Bleeding Risk, Management and Outcome in Patients Receiving Non-VKA Oral Anticoagulants (NOACs).

    PubMed

    Werth, Sebastian; Breslin, Tomás; NiAinle, Fionnuala; Beyer-Westendorf, Jan

    2015-08-01

    Modern direct-acting anticoagulants are rapidly replacing vitamin K antagonists (VKA) in the management of millions of patients worldwide who require anticoagulation. These drugs include agents that inhibit activated factor X (FXa) (such as apixaban and rivaroxaban) or thrombin (such as dabigatran), and are collectively known today as non-VKA oral anticoagulants (NOACs). Since bleeding is the most common and most dangerous side effect of long-term anticoagulation, and because NOACs have very different mechanisms of action and pharmacokinetics compared with VKA, physicians are naturally concerned about the lack of experience regarding frequency, management and outcome of NOAC-associated bleeding in daily care. This review appraises trial and registry (or "real-world") data pertaining to bleeding complications in patients taking NOACs and VKA and provides practical recommendations for the management of acute bleeding situations. PMID:25940651

  19. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

    PubMed Central

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678

  20. [Perioperative management of direct oral anticoagulant in emergency surgery and bleeding. Haemostasis monitoring and treatment].

    PubMed

    Hidalgo, F; Gómez-Luque, A; Ferrandis, R; Llau, J V; de Andrés, J; Gomar, C; Sierra, P; Castillo, J; Torres, L M

    2015-10-01

    There is an almost unanimous consensus on the management of the direct new oral anticoagulants, dabigatran, rivaroxaban, and apixaban in elective surgery. However, this general consensus does not exist in relation with the direct new oral anticoagulants use in emergency surgery, especially in the bleeding patient. For this reason, a literature review was performed using the MEDLINE-PubMed. An analysis was made of the journal articles, reviews, systematic reviews, and practices guidelines published between 2000 and 2014 using the terms "monitoring" and "reversal". From this review, it was shown that the routine tests of blood coagulation, such as the prothrombin time and activated partial thromboplastin time, have a limited efficacy in the perioperative control of blood coagulation in these patients. There is currently no antidote to reverse the effects of these drugs, although the possibility of using concentrated prothrombin complex and recombinant activated factor vii has been suggested for the urgent reversal of the anticoagulant effect.

  1. A Comprehensive Overview of Direct Oral Anticoagulants for the Management of Venous Thromboembolism.

    PubMed

    Comerota, Anthony J; Ramacciotti, Eduardo

    2016-07-01

    Venous thromboembolism (VTE) is a prevalent, potentially fatal health problem. Although standard anticoagulant therapy is effective when compared with the newer direct oral anticoagulants (DOACs), it has disadvantages. Heparin and its derivatives must be administered parenterally, whereas use of oral vitamin K antagonists is complicated by unpredictable pharmacokinetics and pharmacodynamics, drug-food and drug-drug interactions and the requirement for frequent laboratory monitoring. Randomized phase 3 trials have demonstrated that patients receive similarly effective anticoagulation with the DOACs dabigatran, edoxaban, rivaroxaban and apixaban when compared with warfarin, with similar or reduced risk of bleeding. Extended therapy trials have consistently demonstrated superior effectiveness for DOAC treatment when compared with placebo in preventing VTE recurrence. This article presents a comprehensive review of the pharmacokinetics, pharmacodynamics and accumulated clinical trial evidence for each DOAC for short-term, long-term and extended VTE therapy, and it considers the potential implications these agents have for the clinical management of VTE. PMID:27432042

  2. Trials of Novel Oral Anticoagulants for Stroke Prevention In Patients with Non-valvular Atrial Fibrillation

    PubMed Central

    Halperin, Jonathan L; Dorian, Paul

    2014-01-01

    Patients with non-valvular atrial fibrillation (AF) face an increased risk of stroke compared with those in normal sinus rhythm. The vitamin K antagonist warfarin, available for over half a century, is highly effective in reducing the risk of stroke in patients with AF, but it is a difficult drug to use properly. As a result, it is challenging to keep the anticoagulant effect of warfarin in the desired range. Newer oral anticoagulants (NOACs) that directly inhibit Factor IIa (thrombin) or Factor Xa provide reliable anticoagulation when administer in fixed oral doses without routine coagulation monitoring. This manuscript will review in detail the pivotal trials of these NOACs that led to their approval as well as comment on the factors that should influence their selection. PMID:24821657

  3. [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

    PubMed

    Zeus, Tobias; Kelm, Malte; Bode, Christoph

    2015-08-01

    Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. PMID:26261929

  4. A rapid pro-hemostatic approach to overcome direct oral anticoagulants.

    PubMed

    Thalji, Nabil K; Ivanciu, Lacramioara; Davidson, Robert; Gimotty, Phyllis A; Krishnaswamy, Sriram; Camire, Rodney M

    2016-08-01

    Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that are becoming widely adopted. The ability to reverse their anticoagulant effects is important when serious bleeding occurs or urgent medical procedures are needed. Here, using experimental mouse models of hemostasis, we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence of the anticoagulant effects of these inhibitors. The ability of FXa(I16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability of the active site inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa to persist in plasma. Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis models tested than a noncatalytic antidote that is currently in clinical development. FXa(I16L) also reduces the anticoagulant-associated bleeding in vivo that is induced by the thrombin inhibitor dabigatran. FXa(I16L) may be able to fill an important unmet clinical need for a rapid, pro-hemostatic agent to reverse the effects of several new anticoagulants. PMID:27455511

  5. [The latest recommendations on the use of new oral anticoagulants in routine practice].

    PubMed

    Witkowski, Michał; Witkowska, Magdalena; Smolewski, Piotr

    2016-01-01

    The use of non-vitamin K antagonist oral anticoagulants (NOACs) has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC) including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice. PMID:26864063

  6. Use of the Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism.

    PubMed

    Riva, Nicoletta; Ageno, Walter

    2016-10-01

    In the past 2 decades, the direct oral anticoagulants (DOACs) have emerged as alternatives to the standard therapy (unfractionated or low-molecular-weight heparin followed by vitamin K antagonists [VKA]), for the acute and extended treatment of venous thromboembolism. The DOACs have a more favorable pharmacologic profile and a predictable anticoagulant response and, therefore, have the potential to overcome some of the limitations associated with the use of VKA. Several ongoing registries are evaluating the use of the DOACs in routine clinical practice and will provide additional information in less selected patient populations. PMID:27637306

  7. Use of novel oral anticoagulant agents in atrial fibrillation: current evidence and future perspective

    PubMed Central

    Madan, Shivanshu; Shah, Shenil; Partovi, Sasan

    2014-01-01

    The increasing availability of novel oral anticoagulants (NOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) offers alternatives for patients currently prescribed warfarin. This article provides a brief overview on the mechanism and clinical use of these drugs as well as a review of the pivotal clinical trials providing the basis for each agent’s safety and efficacy. While these agents are currently Food and Drug Administration (FDA) approved for anticoagulation of patients with nonvalvular AF, additional studies continually emerge offering further insight into the application of these agents in other areas. PMID:25276617

  8. Novel oral anticoagulants for stroke prevention in atrial fibrillation: focus on apixaban.

    PubMed

    Potpara, Tatjana S; Polovina, Marija M; Licina, Marina M; Stojanovic, Radan M; Prostran, Milica S; Lip, Gregory Y H

    2012-06-01

    Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, 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) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality

  9. Clinical experience with novel oral anticoagulants for thromboprophylaxis after elective hip and knee arthroplasty.

    PubMed

    Messerschmidt, Cory; Friedman, Richard J

    2015-04-01

    Anticoagulant medications help to reduce the risk of thromboembolic events after total hip arthroplasty and total knee arthroplasty. Traditionally, this has been accomplished with medications, such as low-molecular-weight heparin and warfarin. However, these traditional anticoagulants possess a variety of shortcomings that leave much room for improvement. A new class of oral anticoagulants is now available, and present a more convenient option for safe and efficacious thromboprophylaxis in post arthroplasty patients, particularly in the outpatient setting. This review focuses on the direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, and the clinical data to date about their use in total hip arthroplasty and total knee arthroplasty patients. PMID:25767271

  10. The predictability of bleeding by prothrombin times sensitive or insensitive to PIVKA during intensive oral anticoagulation.

    PubMed

    Arnesen, H; Smith, P

    1991-02-01

    To evaluate the effect of PIVKA (Proteins Induced by Vitamin K Absence or Antagonism) on the bleeding tendency during oral anticoagulation, we studied consecutive patients intensively treated with warfarin (INR greater than 4.8). The level of anticoagulation was measured with the PIVKA-insensitive Normotest (NT) as well as with the PIVKA-sensitive Thrombotest (TT), and the results are expressed as per cent coagulant activity. The NT/TT ratio was determined. Twenty patients with bleeding episodes had a mean NT/TT ratio of 2.06 as compared to 2.20 in 143 patients without bleeding episodes (p = 0.08). As the NT/TT ratio was not higher in patients with bleedings, we conclude that PIVKA are of no importance for bleeding during anticoagulation with vitamin K antagonists.

  11. 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

  12. 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

  13. Assessment of bleeding during minor oral surgical procedures and extraction in patients on anticoagulant therapy

    PubMed Central

    Jimson, S.; Amaldhas, Julius; Jimson, Sudha; Kannan, I.; Parthiban, J.

    2015-01-01

    Introduction: The risk of postoperative hemorrhage from oral surgical procedures has been a concern in the treatment of patients who are receiving long-term anticoagulation therapy. A study undertaken in our institution to address questions about the amount and severity of bleeding associated with minor outpatient oral surgery procedures by assessing bleeding in patients who did not alter their anticoagulant regimen. Subjects and Methods: Eighty-three patients receiving long-term anticoagulant therapy visited Department of Oral and Maxillofacial Surgery from May 2010 to October 2011 for extractions and minor oral surgical procedures. Each patient was required to undergo preoperative assessment of prothrombin time (PT) and measurement of the international normalized ratio. Fifty-six patients with preoperative PT values within the therapeutic range 3–4 were included in the study. The patients’ age ranged between 30 and 75 years. Application of surgispon was done following the procedure. Extraction of teeth performed with minimal trauma to the surrounding tissues, the socket margins sutured, and sutures removed after 5 days. Results: There was no significant incidence of prolonged or excessive hemorrhage and wound infection and the healing process was normal. PMID:26015691

  14. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention

    PubMed Central

    Habert, Jeffrey Steven

    2016-01-01

    Many primary care physicians are wary about using direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AF). Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF. PMID:27785089

  15. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment.

    PubMed

    Burnett, Allison E; Mahan, Charles E; Vazquez, Sara R; Oertel, Lynn B; Garcia, David A; Ansell, Jack

    2016-01-01

    Venous thromboembolism (VTE) is a serious medical condition associated with significant morbidity and mortality, and an incidence that is expected to double in the next forty years. The advent of direct oral anticoagulants (DOACs) has catalyzed significant changes in the therapeutic landscape of VTE treatment. As such, it is imperative that clinicians become familiar with and appropriately implement new treatment paradigms. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for VTE treatment with the DOACs. When possible, guidance statements are supported by existing published evidence and guidelines. In instances where evidence or guidelines are lacking, guidance statements represent the consensus opinion of all authors of this manuscript and are endorsed by the Board of Directors of the Anticoagulation Forum.The authors of this manuscript first developed a list of pivotal practical questions related to real-world clinical scenarios involving the use of DOACs for VTE treatment. We then performed a PubMed search for topics and key words including, but not limited to, apixaban, antidote, bridging, cancer, care transitions, dabigatran, direct oral anticoagulant, deep vein thrombosis, edoxaban, interactions, measurement, perioperative, pregnancy, pulmonary embolism, reversal, rivaroxaban, switching, \\thrombophilia, venous thromboembolism, and warfarin to answer these questions. Non- English publications and publications > 10 years old were excluded. In an effort to provide practical information about the use of DOACs for VTE treatment, answers to each question are provided in the form of guidance statements, with the intent of high utility and applicability for frontline clinicians across a multitude of care settings.

  16. Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants.

    PubMed

    Chan, Noel C; Eikelboom, John W; Weitz, Jeffrey I

    2016-04-29

    The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy. PMID:27126650

  17. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-08-01

    The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27591448

  18. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-07-01

    The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27590653

  19. [Should we add antiplatelet therapy to oral anticoagulation in patients with atrial fibrillation and vascular disease? Review of available evidence].

    PubMed

    Andreu, José Manuel; Roldán, Vanessa; García-Navarro, Miguel; Ruipérez, Juan Antonio; Valdés, Mariano; Marín, Francisco

    2012-01-01

    Current recommendation is to add antiplatelet drug to oral anticoagulation in patients with atrial fibrillation (AF) and vascular disease. However, it is debatable to join both antithrombotic drugs in stable vascular disease.

  20. Laboratory Measurement of the Anticoagulant Activity of the Target-specific Oral Anticoagulant Agents: A Systematic Review

    PubMed Central

    Cuker, Adam; Siegal, Deborah M.; Crowther, Mark A.; Garcia, David A.

    2014-01-01

    Background The target-specific oral anticoagulant agents (TSOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. Objectives This study’s objective is to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. Methods We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R2 0.92–0.99) and ecarin-based assays (R2 0.92–1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. In terms of rivaroxaban and apixaban, anti-Xa activity is linear (R2 0.89–1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Conclusions Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in TSOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. PMID:25212648

  1. [Restraints to anticoagulation prescription in atrial fibrillation and attitude towards the new oral anticoagulants].

    PubMed

    Pereira-Da-Silva, Tiago; Souto Moura, Teresa; Azevedo, Luísa; Sá Pereira, Margarida; Virella, Daniel; Alves, Marta; Borges, Luís

    2013-01-01

    Introdução e Objetivos: Avaliar a taxa de prescrição de anticoagulantes orais na fibrilhação auricular, os fatores associados à não prescrição, os motivos referidos pelos clínicos para não prescrição de anticoagulantes incluindo os de nova geração e realizar estudo evolutivo a médio prazo. Material e Métodos: Estudo prospetivo sobre casos consecutivos de doentes com fibrilhação auricular com alta hospitalar. Registaram- se os scores CHA2DS2VASc e HASBLED, comorbilidades associadas e a medicação prévia e à data de alta. Na alta hospitalar, o médico assistente indicou em questionário o motivo de não prescrição de anticoagulantes orais e dos novos anticoagulantes orais. Exclusão: contra-indicação absoluta para anticoagulação, CHA2DS2VASc ≤ 1 e doença valvular. Os doentes foram reavaliados um ano após o recrutamento do primeiro doente. Resultados: Identificaram-se 103 candidatos a anticoagulação oral (79,6 ± 8,0 anos; CHA2DS2VASc 5,8 ± 1,4; HASBLED 2,6 ± 1,0; HASBLED ≥ 3 em 55,3%); os anticoagulantes foram prescritos em 34,0%. Fatores associados à não prescrição por ordem decrescente de relevância: uso prévio de antiagregantes, doente acamado e/ou demente, ausência de insuficiência cardíaca e número de fatores de risco hemorrágico. Razões invocadas para não prescrição por ordem decrescente de frequência: risco hemorrágico elevado, pequeno benefício, incapacidade de seguir o esquema terapêutico e dificuldade na monitorização da razão normalizada internacional (INR). Os novos anticoagulantes não foram prescritos e as razões invocadas foram, por ordem decrescente de frequência: informação insuficiente sobre estes fármacos, risco hemorrágico elevado, custo elevado e pequeno benefício. Aos 8,2 ± 2,5 meses de estudo evolutivo 33,3% dos doentes encontravam-se sob anticoagulação sem que os novos anticoagulantes tivessem sido prescritos. Conclusões: Nesta amostra, a taxa de prescrição de

  2. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

    PubMed

    Faraoni, David; Levy, Jerrold H; Albaladejo, Pierre; Samama, Charles-Marc

    2015-01-01

    Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention. PMID:25925382

  3. Comparative Effectiveness of Prestroke Aspirin on Stroke Severity and Outcome

    PubMed Central

    Park, Jong‐Moo; Kang, Kyusik; Cho, Yong‐Jin; Hong, Keun‐Sik; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Ko, Youngchai; Han, Moon‐Ku; Lee, Jun; Cha, Jae‐Kwan; Kim, Dae‐Hyun; Kim, Dong‐Eog; Kim, Joon‐Tae; Choi, Jay Chol; Yu, Kyung‐Ho; Lee, Byung‐Chul; Lee, Ji Sung; Lee, Juneyoung; Gorelick, Philip B.

    2016-01-01

    Objective The effect of prestroke aspirin use on initial severity, hemorrhagic transformation, and functional outcome of ischemic stroke is uncertain. Methods Using a multicenter stroke registry database, patients with acute ischemic stroke of three subtypes (large artery atherosclerosis [LAA], small vessel occlusion [SVO], or cardioembolism [CE]) were identified. NIH stroke scale (NIHSS) and hemorrhagic transformation at presentation and discharge modified Rankin Scale (mRS) were compared between prestroke aspirin users and nonusers. Results Among the 10,433 patients, 1,914 (18.3%) reported prestroke aspirin use. On crude analysis, initial NIHSS scores of aspirin users were higher than nonusers (mean difference: 0.35; 95% confidence interval [CI]: 0.04–0.66). However, a multivariable analysis with an application of inverse probability of treatment weighting based on a propensity score of prestroke aspirin, having an interaction effect of prestroke aspirin use and stroke subtype in the model, showed less stroke severity for aspirin users in LAA, but not in SVO and CE than for nonusers; mean difference in NIHSS scores in LAA was –0.97 (95% CI: –1.45 to –0.49). With respect to hemorrhagic transformation and mRS, no significant interaction effects were found. Prestroke aspirin use increased the risk of hemorrhagic transformation (adjusted odd ratio: 1.34; 95% CI: 1.05–1.73), but decreased the odds of the higher discharge mRS (0.86; 0.76–0.96). Interpretation Prestroke aspirin use may reduce initial stroke severity in atherothrombotic stroke and can improve functional outcome at discharge despite an increase of hemorrhagic transformation irrespective of stroke subtype. Ann Neurol 2016;79:560–568 PMID:26754410

  4. Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration.

    PubMed

    Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S

    2008-10-01

    The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning. PMID:19000263

  5. 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.

  6. Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

    PubMed Central

    Patel, Raj

    2016-01-01

    Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE). For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. PMID:27217793

  7. [Recommendations on use of direct oral anticoagulants in the perioperative period].

    PubMed

    Llau, Juan V; Ferrandis, Raquel; Castillo, Jorge; de Andrés, José; Gomar, Carmen; Gómez-Luque, Aurelio; Hidalgo, Francisco; Torres, Luis M

    2012-10-01

    Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented.

  8. Preventive strategies against bleeding due to nonvitamin K antagonist oral anticoagulants.

    PubMed

    Lessire, Sarah; Sarah, Lessire; Dincq, Anne-Sophie; Anne-Sophie, Dincq; Douxfils, Jonathan; Jonathan, Douxfils; Devalet, Bérangère; Bérangère, Devalet; Nicolas, Jean-Baptiste; Jean-Baptiste, Nicolas; Spinewine, Anne; Anne, Spinewine; Larock, Anne-Sophie; Anne-Sophie, Larock; Dogné, Jean-Michel; Jean-Michel, Dogné; Gourdin, Maximilien; Maximilien, Gourdin; Mullier, François; François, Mullier

    2014-01-01

    Dabigatran etexilate (DE), rivaroxaban, and apixaban are nonvitamin K antagonist oral anticoagulants (NOACs) that have been compared in clinical trials with existing anticoagulants (warfarin and enoxaparin) in several indications for the prevention and treatment of thrombotic events. All NOACs presented bleeding events despite a careful selection and control of patients. Compared with warfarin, NOACs had a decreased risk of intracranial hemorrhage, and apixaban and DE (110 mg BID) had a decreased risk of major bleeding from any site. Rivaroxaban and DE showed an increased risk of major gastrointestinal bleeding compared with warfarin. Developing strategies to minimize the risk of bleeding is essential, as major bleedings are reported in clinical practice and specific antidotes are currently not available. In this paper, the following preventive approaches are reviewed: improvement of appropriate prescription, identification of modifiable bleeding risk factors, tailoring NOAC's dose, dealing with a missed dose as well as adhesion to switching, bridging and anesthetic procedures. PMID:25032218

  9. Preventive Strategies against Bleeding due to Nonvitamin K Antagonist Oral Anticoagulants

    PubMed Central

    Sarah, Lessire; Anne-Sophie, Dincq; Jonathan, Douxfils; Bérangère, Devalet; Jean-Baptiste, Nicolas; Anne, Spinewine; Anne-Sophie, Larock; Jean-Michel, Dogné; Maximilien, Gourdin; François, Mullier

    2014-01-01

    Dabigatran etexilate (DE), rivaroxaban, and apixaban are nonvitamin K antagonist oral anticoagulants (NOACs) that have been compared in clinical trials with existing anticoagulants (warfarin and enoxaparin) in several indications for the prevention and treatment of thrombotic events. All NOACs presented bleeding events despite a careful selection and control of patients. Compared with warfarin, NOACs had a decreased risk of intracranial hemorrhage, and apixaban and DE (110 mg BID) had a decreased risk of major bleeding from any site. Rivaroxaban and DE showed an increased risk of major gastrointestinal bleeding compared with warfarin. Developing strategies to minimize the risk of bleeding is essential, as major bleedings are reported in clinical practice and specific antidotes are currently not available. In this paper, the following preventive approaches are reviewed: improvement of appropriate prescription, identification of modifiable bleeding risk factors, tailoring NOAC's dose, dealing with a missed dose as well as adhesion to switching, bridging and anesthetic procedures. PMID:25032218

  10. Oral anticoagulants and status of antidotes for the reversal of bleeding risk.

    PubMed

    Ebright, Joseph; Mousa, Shaker A

    2015-03-01

    Anticoagulants have been used in clinical practice for more than 50 years. Their indications expand, as more people are diagnosed each year with atrial fibrillation and venous thromboembolism. Vitamin K antagonists have been the most popular choice due to their effectiveness and their ability to reverse bleeding using a known antidote; oral and intravenous vitamin K have long been known to reverse the effects of warfarin. With new classes of anticoagulants making their way onto the market, such as factor Xa inhibitors (rivaroxaban, apixaban) and direct thrombin inhibitors (dabigatran), the need for new reversal agents is paramount. Patients tend to be more receptive to these medications because they do not require routine blood monitoring, can be used at fixed doses, and do not have major drug or food interactions. Antidotes for these medications have shown promise in animal models and are currently in clinical trials.

  11. Who, when, and how to reverse non-vitamin K oral anticoagulants.

    PubMed

    Aronis, Konstantinos N; Hylek, Elaine M

    2016-02-01

    Non-vitamin K oral anticoagulants (NOACs) have been a major addition to our therapeutic armamentarium. They are at least as effective as warfarin in the thromboprophylaxis of non-valvular atrial fibrillation and management of thromboembolic disease, with a more favorable safety profile. Their predictable pharmacokinetics and pharmacodynamics allow for a fixed oral dosing without the need for anticoagulation monitoring. A major concern regarding NOACs is the lack of a readily available antidote to reverse their anticoagulation effect in case of life-threatening bleeding or need for emergent surgery. In this review, we summarize preclinical and clinical data on (a) hemostatic agents used to reverse NOACs, and (b) novel, target-specific NOACs reversal agents under development. The prothrombin complex concentrates, activated prothrombin complex concentrates and recombinant activated factor VII are hemostatic agents that have been assessed in reversing NOACs. Preclinical studies with hemostatic agents report variable results and there is only limited clinical data available to date. Idarucizumab and andexanet alfa are NOAC-specific reversal agents designed to reverse dabigatran and factor Xa inhibitors accordingly. Aripazine is a universal anticoagulation reversal agent. Preclinical studies show promising results and these agents are already in different stages of clinical development. Phase I and II clinical trials demonstrate efficacy in reversing NOACs without major side effects. Until these agents become commercially available, management of patients receiving NOACs who present with major bleeding or require emergent surgery should focus on (a) immediate discontinuation of NOACs, (b) supportive measures or postponing surgery for 12-24 h after the last NOAC dose, and/or PMID:26627486

  12. [Consensus statement: Management of oral anticoagulation for stroke prevention in patients with nonvalvular atrial fibrillation].

    PubMed

    Helms, Thomas Maria; Silber, Sigmund; Schäfer, Andreas; Masuhr, Florian; Palm, Frederick; Darius, Harald; Schrör, Karsten; Bänsch, Dietmar; Bramlage, Peter; Hankowitz, Johannes; Karle, Christoph A; Stargardt, Tom; Weil, Joachim; Geller, Johann Christoph

    2016-09-01

    With the introduction of edoxaban last year in Germany, four nonvitamin K antagonist oral anticoagulants are now available for stroke prevention in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOAC) represent an attractive new option compared to vitamin K antagonists (e.g., warfarin or phenprocoumon) due to simple use and fewer interactions with other drugs or food. Therefore, no INR monitoring and dosage adjustments are required for NOAC. The compelling clinical advantage of NOAC is the dramatic risk reduction of hemorhagic stroke and intracranial bleeding compared to current standard. In addition, total mortality is significantly reduced by 10 %. These effects are demonstrated for all four NOAC (dabigatran, rivaroxaban, apixaban and edoxaban). Therefore, current national and international guidelines recommend NOAC as the preferred option or at least as an attractive alternative compared to the former standard of vitamin K antagonists. The economic impact and reimbursement by Statutory Health Insurance (GKV) is of major importance for treatment in an outpatient setting. For apixaban and edoxaban, an additional benefit was granted by the institution of G‑BA and IQWiG in this clinical setting, whereas dabigatran and rivaroxaban were not assessed due to market entrance prior to 2011 before the AMNOG procedure was initiated. The members of this consensus paper recommend NOAC as the preferred option for patients with nonvalvular atrial fibrillation who are currently not treated with anticoagulant drugs in spite of clear indication for anticoagulation. For new patients with nonvalvular fibrillation, it should be decided on an individual basis which treatment option is adequate for the patient with their respective comorbidities. PMID:27576696

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

    PubMed Central

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

    1996-01-01

    BACKGROUND: 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. AIM: 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). METHOD: 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. RESULTS: 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. CONCLUSION: 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. PMID

  14. Managing a Rivaroxaban Bleed: Understanding the Difficulties in Acute Reversal of the New Oral Anticoagulants through a Case Report

    PubMed Central

    Singh, Robby; Mckay, Paulina

    2014-01-01

    With the arrival of a new generation of oral anticoagulants significant burdens associated with warfarin's use on both the patient and the healthcare system have been alleviated. Nevertheless, a shortfall exists in regard to an agent or protocol for reversal of these new anticoagulants in the setting of an acute bleed. Our case of a patient presenting to the hospital with a vaginal bleed while on rivaroxaban highlights the difficulty in management without a clear protocol or agent for reversal of anticoagulation. PMID:25478253

  15. 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

  16. Novel oral anticoagulants: efficacy, laboratory measurement, and approaches to emergent reversal.

    PubMed

    Gehrie, Eric; Tormey, Christopher

    2015-05-01

    Warfarin, the most commonly used of the vitamin K antagonists, has been a mainstay of oral anticoagulation for decades. However, its usage is limited by morbidity and mortality secondary to bleeding as well as a cumbersome therapeutic monitoring process. In the past several years, a number of competing novel oral anticoagulants (NOACs) have been developed, each of which aspires to match or exceed warfarin's effectiveness while mitigating bleeding risk and eliminating therapeutic monitoring requirements. At present, 1 oral direct thrombin inhibitor and 2 direct factor Xa inhibitors are approved by the US Food and Drug Administration. Here, we compare the clinical efficacy and safety profiles of these new drugs. In addition, we discuss various laboratory assays that may be useful to measure these drugs in certain clinical circumstances. Finally, we discuss emerging strategies to reverse these agents in an emergency. The purpose of this article is to provide a framework for practicing pathologists to advise clinicians on NOAC laboratory measurement and management of NOAC-associated bleeding. PMID:25927153

  17. Perioperative Management of the Direct Oral Anticoagulants: A Case-Based Review.

    PubMed

    Bell, Benjamin R; Spyropoulos, Alex C; Douketis, James D

    2016-10-01

    The periprocedural management of patients on direct oral anticoagulants (DOACs) is a common but potentially challenging clinical problem because there are few prospective studies to guide clinical decisions. Retrospective analyses from randomized trials and observational data suggest that DOACs can be managed in a standardized manner, based on surgical and patient characteristics, that does not result in excess major bleeding or thrombosis. In a case-based manner, this article presents a perioperative DOAC management algorithm and reviews the available and emerging evidence supporting the safety and efficacy of this approach. A free online clinical guidance tool is available from Thrombosis Canada that includes the proposed management algorithm. PMID:27637308

  18. Perioperative Management of the Direct Oral Anticoagulants: A Case-Based Review.

    PubMed

    Bell, Benjamin R; Spyropoulos, Alex C; Douketis, James D

    2016-10-01

    The periprocedural management of patients on direct oral anticoagulants (DOACs) is a common but potentially challenging clinical problem because there are few prospective studies to guide clinical decisions. Retrospective analyses from randomized trials and observational data suggest that DOACs can be managed in a standardized manner, based on surgical and patient characteristics, that does not result in excess major bleeding or thrombosis. In a case-based manner, this article presents a perioperative DOAC management algorithm and reviews the available and emerging evidence supporting the safety and efficacy of this approach. A free online clinical guidance tool is available from Thrombosis Canada that includes the proposed management algorithm.

  19. [Laboratory coagulation tests in patients treated by direct oral anticoagulants (DOACs)].

    PubMed

    Sié, Pierre

    2015-01-01

    Routine clotting time assays (Prothrombin Time/INR, activated Partial Thromboplastin Time [aPTT]) are prolonged at variable extent by direct oral anticoagulants (DOAC), according to the assay, the reagent and the type of DOAC. These assays are not reliable for monitoring the intensity of treatment and the measurement of the plasma level of the DOAC is usually not required. At high concentrations, DOAC interfere with the routine clotting assays, making them difficult to interpret. In critical situations such as major bleeding or urgent invasive procedure, the measurement of DOAC level and its kinetics are simple and useful to manage the patient.

  20. Non-VKA Oral Anticoagulants: Accurate Measurement of Plasma Drug Concentrations

    PubMed Central

    Mani, Helen; Minet, Valentine; Devalet, Bérangère; Chatelain, Bernard; Dogné, Jean-Michel

    2015-01-01

    Non-VKA oral anticoagulants (NOACs) have now widely reached the lucrative market of anticoagulation. While the marketing authorization holders claimed that no routine monitoring is required and that these compounds can be given at fixed doses, several evidences arisen from the literature tend to demonstrate the opposite. New data suggests that an assessment of the response at the individual level could improve the benefit-risk ratio of at least dabigatran. Information regarding the association of rivaroxaban and apixaban exposure and the bleeding risk is available in the drug approval package on the FDA website. These reviews suggest that accumulation of these compounds increases the risk of experiencing a bleeding complication. Therefore, in certain patient populations such as patients with acute or chronic renal impairment or with multiple drug interactions, measurement of drug exposure may be useful to ensure an optimal treatment response. More specific circumstances such as patients experiencing a haemorrhagic or thromboembolic event during the treatment duration, patients who require urgent surgery or an invasive procedure, or patient with a suspected overdose could benefit from such a measurement. This paper aims at providing guidance on how to best estimate the intensity of anticoagulation using laboratory assays in daily practice. PMID:26090400

  1. 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.

  2. Non-VKA Oral Anticoagulants: Accurate Measurement of Plasma Drug Concentrations.

    PubMed

    Douxfils, Jonathan; Mani, Helen; Minet, Valentine; Devalet, Bérangère; Chatelain, Bernard; Dogné, Jean-Michel; Mullier, François

    2015-01-01

    Non-VKA oral anticoagulants (NOACs) have now widely reached the lucrative market of anticoagulation. While the marketing authorization holders claimed that no routine monitoring is required and that these compounds can be given at fixed doses, several evidences arisen from the literature tend to demonstrate the opposite. New data suggests that an assessment of the response at the individual level could improve the benefit-risk ratio of at least dabigatran. Information regarding the association of rivaroxaban and apixaban exposure and the bleeding risk is available in the drug approval package on the FDA website. These reviews suggest that accumulation of these compounds increases the risk of experiencing a bleeding complication. Therefore, in certain patient populations such as patients with acute or chronic renal impairment or with multiple drug interactions, measurement of drug exposure may be useful to ensure an optimal treatment response. More specific circumstances such as patients experiencing a haemorrhagic or thromboembolic event during the treatment duration, patients who require urgent surgery or an invasive procedure, or patient with a suspected overdose could benefit from such a measurement. This paper aims at providing guidance on how to best estimate the intensity of anticoagulation using laboratory assays in daily practice. PMID:26090400

  3. [Non-VKA oral anticoagulants: an update for the clinical biologists].

    PubMed

    Mullier, François; Douxfils, Jonathan; Tamigniau, Anne; Dogné, Jean-Michel; Horellou, Marie-Hélène; Flaujac, Claire; Chatelain, Bernard; Goffinet, Catherine; Samama, Meyer-Michel; Gouin-Thibault, Isabelle

    2015-01-01

    Non-VKA oral anticoagulants (NOACs), thanks to their ease of use and their similar or superior safety/efficacy profiles versus warfarin, have now widely reached the lucrative market of anticoagulation. However, while the marketing authorization holders always claim, in a quite unclear way that no monitoring is required, accumulative evidence and cases of major bleeding have been described in the literature and reported by spontaneous reporting systems at the regulator's level. These compounds are usually given at fixed doses without routine coagulation monitoring. However, new data suggests that an assessment of the response at the individual level could improve the benefit-risk ratio of, at least dabigatran. Therefore, in certain patient populations, i.e. acute or chronic renal impairment or multiple drug interactions, measurement of drug exposure may be useful to ensure an optimal treatment response. More specific circumstances such as patients experiencing a haemorrhagic or thromboembolic event during the treatment duration, patients who require urgent surgery or an invasive procedure, or patient with a suspected overdose could benefit from such a measurement. This article aims at providing guidance on how to best estimate the intensity of anticoagulation using laboratory assays in daily practice. PMID:25857818

  4. New direct oral anticoagulants--current therapeutic options and treatment recommendations for bleeding complications.

    PubMed

    Miesbach, Wolfgang; Seifried, Erhard

    2012-10-01

    To date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs. PMID:22782297

  5. 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.

  6. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers

    PubMed Central

    Nahar, Risha; Saxena, Renu; Deb, Roumi; Verma, Ishwar C.

    2012-01-01

    CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 *2, *3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 (*2, F*3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes. PMID:23716941

  7. Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs.

    PubMed

    Stöllberger, Claudia; Finsterer, Josef

    2016-10-01

    Atrial fibrillation (AF) is a frequent cause of stroke. Secondary prophylaxis by oral anticoagulants (OAC) is recommended after stroke in AF-patients. OAC can be achieved by vitamin-K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran, rivaroxaban, apixaban or edoxaban. Seizures are frequent after stroke, and antiepileptic drugs (AEDs) are indicated. The review, based on a literature research, aims to give an overview about pharmacokinetic knowledge and clinical data about drug-drug interactions (DDIs) between NOACs and AED. Carbamazepine, levetiracetam, phenobarbital, phenytoin and valproic acid might decrease the effect of NOACs by inducing P-glycoprotein (P-gp) activity. Carbamazepine, oxcarbazepine, phenytoin, phenobarbital and topiramate might decrease the effect of NOACs by inducing CYP3A4 activity. Controversial data - inhibition as well as induction of CYP3A4 - were found about valproic acid. The relevance of these DDIs is largely unknown since there are only sporadic case reports available. To increase the knowledge about DDIs between NOACs and AEDs we suggest subgroup analyses addressing effects and safety of VKAs versus NOACs in patients with AF on AEDs, in case they have been included in previously completed or still ongoing trials or registries. This could be easily feasible and would be desirable in view of the large data already accumulated. PMID:27450623

  8. Management of Non-Vitamin K Antagonist Oral Anticoagulants in the Perioperative Setting

    PubMed Central

    Dincq, Anne-Sophie; Dogné, Jean-Michel; Gourdin, Maximilien

    2014-01-01

    The field of oral anticoagulation has evolved with the arrival of non-vitamin K antagonist oral anticoagulants (NOACs) including an anti-IIa agent (dabigatran etexilate) and anti-Xa agents (rivaroxaban and apixaban). The main specificities of these drugs are predictable pharmacokinetics and pharmacodynamics but special attention should be paid in the elderly, in case of renal dysfunction and in case of emergency. In addition, their perioperative management is challenging, especially with the absence of specific antidotes. Effectively, periods of interruption before surgery or invasive procedures depend on half-life and keeping a permanent balance between bleeding and thromboembolic risks. In addition, few data regarding the link between plasma concentrations and their effects are provided. Routine laboratory tests are altered by NOACs and quantitative measurements are not widely performed. This paper provides a review on the management of NOACs in the perioperative setting, including the estimation of the bleeding and thrombotic risk, the periods of interruption, the indication of heparin bridging, the usefulness of laboratory tests before surgery or invasive procedure, and the time of resuming. Most data are based on expert's opinions. PMID:25276784

  9. Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients.

    PubMed

    Krüger, Thilo; Brandenburg, Vincent; Schlieper, Georg; Marx, Nikolaus; Floege, Jürgen

    2013-03-01

    End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.

  10. Management of non-vitamin K antagonist oral anticoagulants in the perioperative setting.

    PubMed

    Dincq, Anne-Sophie; Lessire, Sarah; Douxfils, Jonathan; Dogné, Jean-Michel; Gourdin, Maximilien; Mullier, François

    2014-01-01

    The field of oral anticoagulation has evolved with the arrival of non-vitamin K antagonist oral anticoagulants (NOACs) including an anti-IIa agent (dabigatran etexilate) and anti-Xa agents (rivaroxaban and apixaban). The main specificities of these drugs are predictable pharmacokinetics and pharmacodynamics but special attention should be paid in the elderly, in case of renal dysfunction and in case of emergency. In addition, their perioperative management is challenging, especially with the absence of specific antidotes. Effectively, periods of interruption before surgery or invasive procedures depend on half-life and keeping a permanent balance between bleeding and thromboembolic risks. In addition, few data regarding the link between plasma concentrations and their effects are provided. Routine laboratory tests are altered by NOACs and quantitative measurements are not widely performed. This paper provides a review on the management of NOACs in the perioperative setting, including the estimation of the bleeding and thrombotic risk, the periods of interruption, the indication of heparin bridging, the usefulness of laboratory tests before surgery or invasive procedure, and the time of resuming. Most data are based on expert's opinions. PMID:25276784

  11. 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

  12. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    PubMed Central

    Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  13. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians.

    PubMed

    Peacock, W Frank; Rafique, Zubaid; Singer, Adam J

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban, and edoxaban-have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  14. Non-Vitamin K Oral Anticoagulants in Stroke Patients: Practical Issues

    PubMed Central

    Diener, Hans-Christoph; Kleinschnitz, Christoph

    2016-01-01

    Non-vitamin-K oral anticoagulants (NOACs) represent a major advance in the prevention of stroke in patients with atrial fibrillation (AF), offering a similar, if not superior, efficacy and safety profile and several practical advantages over oral vitamin K antagonists (VKAs). The rapid onset of action of the NOACs, their relatively short half-live, and the availability of specific reversal agents may be advantageous when managing acute ischemic strokes, and in the post-stroke, post-transient ischemic attack, and post-intracranial hemorrhage settings. In this review article, we offer practical guidance on the use of NOACs in these settings, focusing on managing the acute event and on initiating or resuming anticoagulation for secondary prevention. We also assess the use of NOACs to prevent stroke and bleeding in patients with AF who have chronic kidney disease, are elderly, or cognitively impaired, and we offer guidance on optimizing the use of NOACs and VKAs in these patient groups in the absence of evidence-based guidelines. PMID:27165264

  15. Survival of heparins, oral anticoagulants, and aspirin after the year 2010.

    PubMed

    Fareed, Jawed; Hoppensteadt, Debra A; Fareed, Daniel; Demir, Muzaffer; Wahi, Rakesh; Clarke, Melaine; Adiguzel, Cafer; Bick, Rodger

    2008-02-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a refined use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including specific sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-specific serine protease inhibitor complexes have also been developed. There is a major thrust on the development of orally bioavailable anticoagulant drugs (anti-Xa and anti-IIa agents), which are slated to replace oral anticoagulants. Both the anti-factor Xa and antithrombin agents have been developed for oral use and have provided impressive clinical outcomes in sponsor trials for the postsurgical prophylaxis of venous thrombosis; however, safety concerns related to liver enzyme elevations and

  16. A clinician’s perspective: novel oral anticoagulants to reduce the risk of stroke in nonvalvular atrial fibrillation – full speed ahead or proceed with caution?

    PubMed Central

    Yang, Eugene

    2014-01-01

    Over the past few years, three novel oral anticoagulants, dabigatran, rivaroxaban, and apixaban, have been approved in the USA and Europe to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation, and the results of a Phase III trial for a fourth novel oral anticoagulant, edoxaban, have recently been published. The aim of this review is to examine this indication from a clinician’s perspective, highlighting efficacy and safety results from the major trials with these novel oral agents. Clinical issues regarding bleeding, monitoring, and reversal are discussed, along with requirements to consider when interrupting treatment with a novel oral anticoagulant for the purpose of transitioning to another anticoagulant and prior to cardioversion, ablation, percutaneous coronary intervention, or emergency surgery. The cost-effectiveness of each of the approved novel oral anticoagulants is reviewed, and the author provides recommendations for selecting appropriate patients for these agents. PMID:25187724

  17. EDUC’AVK: Reduction of Oral Anticoagulant-related Adverse Events After Patient Education: A Prospective Multicenter Open Randomized Study

    PubMed Central

    Labarère, José; Yver, Jacqueline; Satger, Bernadette; Allenet, Benoit; Berremili, Touffek; Fontaine, Michèle; Franco, Guy; Bosson, Jean Luc

    2008-01-01

    Background Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown. Objective To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications. Design/Participants We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events. Results During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 – 0.7,  < 0.01). Conclusions Patient education using an educational program reduced VKA-related adverse event rates. PMID:18566863

  18. Help Desk Answers: Do novel oral anticoagulants safely prevent stroke in patients with nonvalvular A-fib?

    PubMed

    Siewert, Ryan; Hostetter, Jeff

    2016-06-01

    Yes. Dabigatran, rivaroxaban, and apixaban are safe and effective compared with warfarin for preventing stroke in patients with nonvalvular atrial fibrillation. These novel oral anticoagulants (NOACs) are noninferior in reducing the number of strokes and systemic emboli and in lowering all-cause mortality while not increasing major bleeding complications and hemorrhagic events. PMID:27474824

  19. Patient self management of oral anticoagulation in routine care in the UK

    PubMed Central

    McCahon, D; Murray, E T; Jowett, S; Sandhar, H S; Holder, R L; Hussain, S; O'Donoghue, B; Fitzmaurice, D A

    2007-01-01

    Background Self management of anticoagulation: a randomised trial (SMART) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management (PSM) of oral anticoagulation therapy compared to routine care. SMART showed that while PSM was as clinically effective as routine care, it was not as cost effective. SMART adds to the growing body of trial data to support PSM; however there are no data on clinical effectiveness and cost of PSM in routine care. Aim To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions. Methods A retrospective multicentre matched control study. 63 PSM patients from primary care in the West Midlands were matched by age and international normalised ratio (INR) target with controls. INR results were collected for the period 1 July 2003–30 June 2004. The primary outcome measure was INR control. Results 38 PSM and 40 control patients were recruited. INR percentage time in range was 70% PSM vs 64% controls. 60% PSM were having a regular clinical review, 45% were performing an internal quality control (IQC) test and 82% were performing external quality assurance (EQA) on a regular basis. Conclusion PSM outside trial conditions is as clinically effective as routine UK care. PMID:17259295

  20. Axillary artery pseudoaneurysm resulting in brachial plexus injury in a patient taking new oral anticoagulants.

    PubMed

    Monem, Mohammed; Iskandarani, Mohamad Khalid; Gokaraju, Kishan

    2016-01-01

    We discuss the case of an independent 80-year-old Caucasian woman, being treated with new oral anticoagulants for a previous deep vein thrombosis, who had fallen on her right shoulder. She made a delayed presentation to the emergency department with a wrist drop in her right dominant hand. She had right arm bruising with good distal pulses but had a global neurological deficit in the hand. Plain radiographs of the shoulder, humerus, elbow, forearm and wrist demonstrated no fractures. MRI showed a significant right axillary lesion distorting the surrounding soft tissues, including the brachial plexus, and CT with contrast confirmed this to be a large axillary pseudoaneurysm. This was treated with an endovascular stent resulting in slightly improved motor function, but the significant residual deficit required subsequent rehabilitation to improve right upper limb function. PMID:27535738

  1. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants

    PubMed Central

    Nakashima, Megan O.

    2014-01-01

    Hypercoagulability can result from a variety of inherited and, more commonly, acquired conditions. Testing for the underlying cause of thrombosis in a patient is complicated both by the number and variety of clinical conditions that can cause hypercoagulability as well as the many potential assay interferences. Using an algorithmic approach to hypercoagulability testing provides the ability to tailor assay selection to the clinical scenario. It also reduces the number of unnecessary tests performed, saving cost and time, and preventing potential false results. New oral anticoagulants are powerful tools for managing hypercoagulable patients; however, their use introduces new challenges in terms of test interpretation and therapeutic monitoring. The coagulation laboratory plays an essential role in testing for and treating hypercoagulable states. The input of laboratory professionals is necessary to guide appropriate testing and synthesize interpretation of results. PMID:25025009

  2. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants.

    PubMed

    Nakashima, Megan O; Rogers, Heesun J

    2014-06-01

    Hypercoagulability can result from a variety of inherited and, more commonly, acquired conditions. Testing for the underlying cause of thrombosis in a patient is complicated both by the number and variety of clinical conditions that can cause hypercoagulability as well as the many potential assay interferences. Using an algorithmic approach to hypercoagulability testing provides the ability to tailor assay selection to the clinical scenario. It also reduces the number of unnecessary tests performed, saving cost and time, and preventing potential false results. New oral anticoagulants are powerful tools for managing hypercoagulable patients; however, their use introduces new challenges in terms of test interpretation and therapeutic monitoring. The coagulation laboratory plays an essential role in testing for and treating hypercoagulable states. The input of laboratory professionals is necessary to guide appropriate testing and synthesize interpretation of results.

  3. [Pharmacogenetics of oral anticoagulants: individualized drug treatment for more efficacy and safety].

    PubMed

    Loriot, Marie-Anne; Beaune, Philippe

    2007-06-30

    Oral anti-vitamin K (AVK) anticoagulants constitute the first cause of iatrogenic accidents in France because of narrow therapeutic index and bleeding risk. The wide interindividual variation in AVK response is partly genetically determined. The main enzyme responsible for the metabolism of AVK is the hepatic cytochrome P450 2C9 (CYP2C9). Vitamine K epoxide reductase complex subunit I (VKORC1) is a key enzyme in the vitamin K cycle, cofactor required for the activation of vitamin K-dependent clotting factors, and is the target enzyme of AVK inhibition. Genetic variations affecting both CYP2C9 and VKORC1 are associated with variability in drug response and may explain differences in dose requirements. Genotyping for CYP2C9 and VKORC1 variants before initiation of treatment may allow clinicians to develop dosing protocols and identify the patients at a higher risk for bleeding complications.

  4. Net Clinical Benefit of Oral Anticoagulants: A Multiple Criteria Decision Analysis

    PubMed Central

    Yang, Yea-Huei Kao; Lu, Christine Y.

    2015-01-01

    Background This study quantitatively evaluated the comparative efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, and apizaban) and warfarin for treatment of nonvalvular atrial fibrillation. We also compared these agents under different scenarios, including population with high risk of stroke and for primary vs. secondary stroke prevention. Methods We used multiple criteria decision analysis (MCDA) to assess the benefit-risk of these medications. Our MCDA models contained criteria for benefits (prevention of ischemic stroke and systemic embolism) and risks (intracranial and extracranial bleeding). We calculated a performance score for each drug accounting for benefits and risks in comparison to treatment alternatives. Results Overall, new agents had higher performance scores than warfarin; in order of performance scores: dabigatran 150 mg (0.529), rivaroxaban (0.462), apixaban (0.426), and warfarin (0.191). For patients at a higher risk of stroke (CHADS2 score≥3), apixaban had the highest performance score (0.686); performance scores for other drugs were 0.462 for dabigatran 150 mg, 0.392 for dabigatran 110 mg, 0.271 for rivaroxaban, and 0.116 for warfarin. Dabigatran 150 mg had the highest performance score for primary stroke prevention, while dabigatran 110 mg had the highest performance score for secondary prevention. Conclusions Our results suggest that new oral anticoagulants might be preferred over warfarin. Selecting appropriate medicines according to the patient’s condition based on information from an integrated benefit-risk assessment of treatment options is crucial to achieve optimal clinical outcomes. PMID:25897861

  5. Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures.

    PubMed

    Mar, Philip L; Familtsev, Dmitry; Ezekowitz, Michael D; Lakkireddy, Dhanunjaya; Gopinathannair, Rakesh

    2016-01-01

    An increasing number of individuals are on novel oral anticoagulants (NOAC) for anticoagulation instead of vitamin K antagonists (VKA) and roughly 10% of these individuals will require interruption of these agents for procedures annually. Recent evidence surrounding bridging as well as the FDA approval of a new NOAC call for a comprehensive review and update regarding periprocedural NOAC management. The periprocedural management of NOACs involves striking a balance between the risks of bleeding and thromboembolism associated with interruption, bridging, and reinitiation of anticoagulation. NOACs have a distinct pharmacokinetic advantage in this setting with their quick onset and elimination from the body. Procedures at low risk for bleeding do not require interruption and can be scheduled at the start of the next dosing interval. Procedures at moderate-high risk of bleeding require interruption of NOAC for 5 half lives prior to the procedure to allow for adequate elimination of the drug. In light of new evidence highlighting the risks of bleeding, and given shorter "unprotected" times with NOAC interruption versus VKA, patients at low-moderate risk for thromboembolism should not be bridged when "unprotected" time is less than 96 h. For patients at high risk for thromboembolism, individual patient and surgical factors need to be considered before the decision to bridge is made. The benefit of bridging these patients who have a considerable risk of bleeding may not outweigh the benefits. Focused randomized studies on periprocedural management of NOACs are urgently needed. PMID:26447666

  6. 'Ins' and 'outs' of triple therapy: Optimal antiplatelet therapy in patients on chronic oral anticoagulation who need coronary stenting.

    PubMed

    Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M

    2010-09-01

    Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).

  7. Preclinical safety evaluation of low molecular weight heparin-deoxycholate conjugates as an oral anticoagulant.

    PubMed

    Kim, Ji-young; Jeon, Ok-Cheol; Moon, Hyun Tae; Hwang, Seung Rim; Byun, Youngro

    2016-01-01

    The preclinical safety of a newly developed oral anticoagulant, the low molecular weight heparin-deoxycholate conjugate (OH09208), was evaluated by a comprehensive evaluating program in compliance with standard guidelines. The single dose oral toxicity study in rats receiving 2000 and 5000 mg kg(-1) of OH09208 did not reveal any mortality, unusual body weight changes or necropsy findings. The results of the 4-week oral toxicity study with a 4-week recovery program in rats receiving OH09208 in doses of 100, 300 and 1000 mg kg(-1) day(-1) did not reveal any mortality, or indicate any unusual clinical signs, or show any toxicokinetic relationships to the administration of OH09208. Although the increase in liver enzymes in one male dog treated with 300 mg kg(-1) day(-1) and one female dog treated with 1000 mg kg(-1) day(-1) could not be excluded from the effect of the test substance, no other toxicologically significant changes were observed in the 4-week oral toxicity study with a 4-week recovery in beagle dogs. Thus, while the no-observed-adverse-effect level value from the 4-week study in both male and female rats was 1000 mg kg(-1) day(-1), those from the 4-week study in male and female beagle dogs were 300 and 1000 mg kg(-1) day(-1), respectively. Furthermore, OH09208 did not induce anaphylactic reactions in guinea pigs, micronucleated bone marrow cells in male ICR mice, chromosomal aberration in Chinese hamster lung cell lines, bacterial reverse mutation, and any abnormalities in hERG current assay, mouse central nervous system and dog cardiovascular studies. Overall, there were no unexpected toxicities in this preclinical study that might have precluded the safe administration of OH09208 to humans.

  8. Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

    PubMed Central

    Wilson, Duncan; Charidimou, Andreas; Shakeshaft, Clare; Ambler, Gareth; White, Mark; Cohen, Hannah; Yousry, Tarek; Al-Shahi Salman, Rustam; Lip, Gregory Y.H.; Brown, Martin M.; Jäger, Hans Rolf

    2016-01-01

    Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non–vitamin K oral anticoagulants (NOAC)–associated ICH to warfarin-associated ICH. Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3–5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0–21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH. PMID:26718576

  9. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting.

    PubMed

    Beyer-Westendorf, Jan; Michalski, Franziska; Tittl, Luise; Middeldorp, Saskia; Cohen, Hannah; Abdul Kadir, Rezan; Arachchillage, Deepa Jayakody; Arya, Roopen; Ay, Cihan; Marten, Sandra

    2016-09-27

    Today, direct oral anticoagulants (DOAC) are widely used alternatives to Vitamin-K antagonists (VKA). Women of reproductive age may become pregnant during anticoagulation and, while VKA carry an embryotoxic potential, the risk of DOAC embryopathy is unknown. As a result, some patients elect to terminate pregnancy for fear of DOAC embryotoxicity. To assess the risk of DOAC embryopathy, we reviewed cases of DOAC exposure in pregnancy collected from physicians, literature and pharmacovigilance systems of drug authorities and manufacturers. A total of 357 reports including duplicates were available from which 233 unique cases could be identified. Information on pregnancy outcome was available in only 137/233 cases (58.8 %): 67 live births (48.9 %); 31 miscarriages (22.6 %); 39 elective pregnancy terminations (28.5 %). In 93 cases (39.9 %) no outcome data were available (including 3 cases of ongoing pregnancy). Of the 137 pregnancies with reported outcomes, seven showed abnormalities (5.1 %) of which three (2.2 %) could potentially be interpreted as embryopathy: live birth with facial dysmorphism; miscarriage in week 10 with limb abnormality; elective pregnancy termination due to a foetal cardiac defect in a woman who had to terminate a previous pregnancy due to Fallot tetralogy. Within its limitations (small numbers, incomplete outcome data) our results do not indicate that DOAC exposure in pregnancy carries a high risk of embryopathy or that DOAC exposure per se should be used to direct patient counselling towards pregnancy termination. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases indicating the strong need for a more robust system of reporting. PMID:27384740

  10. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    PubMed Central

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  11. Pregnancy outcome in patients exposed to direct oral anticoagulants - and the challenge of event reporting.

    PubMed

    Beyer-Westendorf, Jan; Michalski, Franziska; Tittl, Luise; Middeldorp, Saskia; Cohen, Hannah; Abdul Kadir, Rezan; Arachchillage, Deepa Jayakody; Arya, Roopen; Ay, Cihan; Marten, Sandra

    2016-09-27

    Today, direct oral anticoagulants (DOAC) are widely used alternatives to Vitamin-K antagonists (VKA). Women of reproductive age may become pregnant during anticoagulation and, while VKA carry an embryotoxic potential, the risk of DOAC embryopathy is unknown. As a result, some patients elect to terminate pregnancy for fear of DOAC embryotoxicity. To assess the risk of DOAC embryopathy, we reviewed cases of DOAC exposure in pregnancy collected from physicians, literature and pharmacovigilance systems of drug authorities and manufacturers. A total of 357 reports including duplicates were available from which 233 unique cases could be identified. Information on pregnancy outcome was available in only 137/233 cases (58.8 %): 67 live births (48.9 %); 31 miscarriages (22.6 %); 39 elective pregnancy terminations (28.5 %). In 93 cases (39.9 %) no outcome data were available (including 3 cases of ongoing pregnancy). Of the 137 pregnancies with reported outcomes, seven showed abnormalities (5.1 %) of which three (2.2 %) could potentially be interpreted as embryopathy: live birth with facial dysmorphism; miscarriage in week 10 with limb abnormality; elective pregnancy termination due to a foetal cardiac defect in a woman who had to terminate a previous pregnancy due to Fallot tetralogy. Within its limitations (small numbers, incomplete outcome data) our results do not indicate that DOAC exposure in pregnancy carries a high risk of embryopathy or that DOAC exposure per se should be used to direct patient counselling towards pregnancy termination. Pregnancy outcome data are inconsistently captured in pharmacovigilance databases indicating the strong need for a more robust system of reporting.

  12. Managing venous thromboembolism in Asia: winds of change in the era of new oral anticoagulants.

    PubMed

    Cohen, Alexander; Chiu, Kuan Ming; Park, Kihyuk; Jeyaindran, Sinnadurai; Tambunan, Karmel L; Ward, Christopher; Wong, Raymond; Yoon, Sung-Soo

    2012-09-01

    Despite advances in the management of venous thromboembolism (VTE), treatment of many patients worldwide, especially in Asia, remains inadequate and/or discordant with prevailing guidelines. Although epidemiological studies consistently report lower incidences of VTE in Asians than Caucasians, VTE rates in Asia have probably been gravely underestimated, partly due to comparatively lesser ascertainment. It is becoming evident that Asians are at much higher risk of VTE than was hitherto supposed. Nevertheless, VTE risk-assessment is not routine in Asia and thromboprophylaxis rates are much lower than in Western nations. It is important to base decisions about anticoagulation on individual circumstances and weigh the potential benefits and risks. The conventional VTE management paradigm is not ideal. New oral anticoagulants offer advantages over current modalities that may help to streamline patient care and reduce healthcare costs. Initially, they will be mainly used in uncomplicated cases and, in the absence of clear differences in efficacy or safety, convenience, tolerability/adherence and cost will determine treatment choice. There is clear scope to improve VTE prevention and treatment in Asia. Key priorities are raising awareness of best practice and properly implementing guidelines. Uncertainty about the burden of VTE and concern about bleeding are barriers. High-quality Asian epidemiological data are needed to guide healthcare policy and evidence-based practice. More data on the occurrence and management of bleeding complications in Asian patients are also required. Meanwhile, physicians should remain vigilant and strive to act early, decisively and appropriately to diagnose and treat VTE, particularly in patients at high risk. PMID:22766512

  13. Efficacy of Oral Anticoagulation in Stroke Prevention among Sinus-Rhythm Patients Who Lack Left Atrial Mechanical Contraction after Cryoablation.

    PubMed

    Martínez-Comendador, José; Gualis, Javier; Marcos-Vidal, José Miguel; Buber, Jonnatan; Martín, Carlos Esteban; Gomez-Plana, Jesús; Rodríguez, Miguel Angel; Iglesias-Garriz, Ignacio; Alonso, David; Soria, Carlos; Miguélez, Eva Higuera; Castaño, Mario

    2015-10-01

    The customary recommendation is that oral anticoagulation be withdrawn a few months after cryoablation for atrial fibrillation, independently of left atrial mechanical contraction in patients in sinus rhythm. Recently, a 5-fold increase in stroke has been described in sinus-rhythm patients who lack atrial mechanical contraction. One aim of this study was to evaluate the efficacy of oral anticoagulation in preventing postoperative stroke in such patients. This prospective study divided 154 sinus-rhythm patients into 2 groups, depending on the presence (108 patients) or absence (46 patients) of left atrial mechanical contraction at 6 months after surgery, and monitored them annually for 5 years. Those without left atrial contraction were maintained on acenocumarol. The primary endpoint was the occurrence of ischemic stroke. The median follow-up period was 29 ± 16 months; 4 patients (2.5%), all belonging to the group with preserved atrial contraction, had ischemic stroke; the group of patients without left atrial contraction had no episodes of stroke during follow-up. Logistic binary regression analyses showed no evidence of factors independently predictive of stroke. Among anticoagulated patients in sinus rhythm without left atrial contraction, we found the incidence of stroke to be zero. In a small, nonrandomized group such as this, we cannot discount the element of chance, yet we suggest that maintaining anticoagulation might lower the incidence of stroke in this population.

  14. A new plastic collection tube made of polyethylene terephtalate is suitable for monitoring traditional anticoagulant therapy (oral anticoagulant, unfractionated heparin, and low molecular weight heparin).

    PubMed

    Toulon, Pierre; Ajzenberg, Nadine; Smahi, Motalib; Guillin, Marie-Claude

    2007-01-01

    To improve the safety of blood collection, plastic tubes have been developed but various interactions with the coagulation system and/or antithrombotic drugs were reported with the first generation of such tubes. The aim of this multicentre study was to compare hemostasis test results measured in evacuated plastic tubes made of polyethylene terephtalate (VenoSafe, Terumo Europe) and in siliconized glass tubes containing the same citrate concentration (0.129 M). In addition, the impact of aging of the plastic tube was investigated by collecting blood samples in tubes at 8 months and at 1 month before expiry. Blood was drawn in 3 centres from untreated patients (n=269), patients on oral anticoagulant treatment (OAT, n=221), and patients treated with either unfractionated heparin (UFH, n=73) or a low molecular weight derivative (LMWH, n=48). Prothrombin time (PT) or INR, activated partial thromboplastin time (APTT) and anti-FXa activity were locally performed, when applicable. In untreated patients and in patients on OAT, PT and APTT values were found statistically shorter (p<0.05) when evaluated in plastic tubes than in glass tubes, except when PT was evaluated using a human thromboplastin. Surprisingly, significantly longer APTT and higher anti-FXa activities were obtained when blood from patients on UFH was drawn in plastic than in glass tubes. However, none of the differences had any clinical relevance (Bland-Altman analysis). In patients on anticoagulant treatment, there was no effect of aging of the plastic tubes. These results suggest that the plastic tube VenoSafe is suitable for coagulation testing both in untreated subjects and more interestingly in patients on traditional anticoagulant therapy during the whole shelf life indicated by the manufacturer. PMID:16426667

  15. Antiplatelet therapy strategies after percutaneous coronary intervention in patients needing oral anticoagulation.

    PubMed

    Saint Etienne, Christophe; Angoulvant, Denis; Simeon, Edouard; Fauchier, Laurent

    2013-11-01

    Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies.

  16. 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.

  17. Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis.

    PubMed

    Illán-Gala, Ignacio; Martínez-Sánchez, Patricia; Fuentes, Blanca; Llamas-Osorio, Yudy; Díaz de Terán, Javier; Báez, Melissa; Ruiz-Ares, Gerardo; Sanz-Cuesta, Borja Enrique; Lara-Lara, Manuel; Díez-Tejedor, Exuperio

    2016-07-01

    Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010-2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5-1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5-1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006-4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173-3.789) as well as INR 1.5-1.9 (OR 3.676, 95 % CI 1.510-8.946) were associated with favorable outcomes (mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT. PMID:26860861

  18. Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

    PubMed

    De Caterina, Raffaele; Husted, Steen; Wallentin, Lars; Andreotti, Felicita; Arnesen, Harald; Bachmann, Fedor; Baigent, Colin; Collet, Jean-Philippe; Halvorsen, Sigrun; Huber, Kurt; Jespersen, Jørgen; Kristensen, Steen Dalby; Lip, Gregory Y H; Morais, João; Rasmussen, Lars Hvilsted; Ricci, Fabrizio; Sibbing, Dirk; Siegbahn, Agneta; Storey, Robert F; Ten Berg, Jurriën; Verheugt, Freek W A; Weitz, Jeffrey I

    2016-04-01

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice. PMID:26952877

  19. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation.

    PubMed

    Borgman, Mark P; Pendleton, Robert C; McMillin, Gwendolyn A; Reynolds, Kristen K; Vazquez, Sara; Freeman, Andrew; Wilson, Andrew; Valdes, Roland; Linder, Mark W

    2012-09-01

    We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management. PMID:22836303

  20. Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

    USGS Publications Warehouse

    Vyas, Nimish B.; Rattner, Barnett A.

    2012-01-01

    Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

  1. Use of oral anticoagulants in African-American and Caucasian patients with atrial fibrillation: is there a treatment disparity?

    PubMed

    Akinboboye, Olakunle

    2015-01-01

    Atrial fibrillation (AF) is a very common cardiac arrhythmia, and its prevalence is increasing along with aging in the developed world. This review discusses racial differences in the epidemiology and treatment of AF between African-American and Caucasian patients. Additionally, the effect of race on warfarin and novel oral anticoagulant use is discussed, as well as the role that physicians and patients play in achieving optimal treatment outcomes. Despite having a lower prevalence of AF compared with Caucasians, African-Americans suffer disproportionately from stroke and its sequelae. The possible reasons for this paradox include poorer access to health care, lower health literacy, and a higher prevalence of other stroke-risk factors among African-Americans. Consequently, it is important for providers to evaluate the effects of race, health literacy, access to health care, and cultural barriers on the use of anticoagulation in the management of AF. Warfarin-dose requirements vary across racial groups, with African-American patients requiring a higher dose than Caucasians to maintain a therapeutic international normalized ratio; the novel oral anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to differ in this regard, although data are currently limited. Minority racial groups are not proportionally represented in either real-world studies or clinical trials, but as more information becomes available and other social issues are addressed, the treatment disparities between African-American and Caucasian patients should decrease. PMID:26056467

  2. Novel Oral Anticoagulants for Venous Thromboembolism with Special Emphasis on Risk of Hemorrhagic Complications and Reversal Agents

    PubMed Central

    Ahmed, Zaheer; Hassan, Seemeen; Salzman, Gary A.

    2016-01-01

    Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes. This review summarizes the major trials that led to the approval of these agents and their exclusion criteria helping physicians understand which patient types might not benefit from these agents. It provides clinical pearls invaluable in everyday practice such as transitioning between traditional and novel anticoagulants, dose adjustments for high risk populations, drug interactions and cost analysis. Futhermore, the review provides direct comparisons with warfarin and indirect comparisons among the novel agents in terms of efficacy and bleeding risk narrating the numbers of patients with intracranial, gastrointestinal and fatal hemorrhages in each of the major trials. We hope that this review will help the physicians inform their patients about the benefits and risks of these agents and enable them to make an informed selection of the most appropriate anticoagulant. PMID:27594818

  3. 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.

  4. The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation.

    PubMed

    Kuznetsov, Sofya; Barcelona, Robert; Josephson, Richard A; Mohan, Sri K Madan

    2016-05-01

    Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC. PMID:27023335

  5. New orally active anticoagulant agents for the prevention and treatment of venous thromboembolism in cancer patients

    PubMed Central

    Gerotziafas, Grigoris T; Mahé, Isabelle; Elalamy, Ismail

    2014-01-01

    Patients with cancer have a 6–7-fold higher risk of venous thromboembolism (VTE) as compared with non-cancer patients. Effective and safe anticoagulation for the prevention and treatment of VTE is the cornerstone of the management of patients with cancer, aiming to decrease morbidity and mortality and to improve quality of life. Unfractionated heparin, low molecular weight heparins, fondaparinux and vitamin K antagonists (VKAs) are used in the prevention and treatment of VTE in cancer patients. Heparins and fondaparinux are administered subcutaneously. VKAs are orally active, but they have a narrow therapeutic window, numerous food and drug interactions, and treatment requires regular laboratory monitoring and dose adjustment. These limitations among others have important negative impact on the quality of life of patients and decrease adherence to the treatment. New orally active anticoagulant (NOAC) agents are specific inhibitors of activated factor Xa (FXa) (rivaroxaban and apixaban) or thrombin (dabigatran). It is expected that NOACs will improve antithrombotic treatment. Cancer patients are a particular group that could benefit from treatment with NOACs. However, NOACs present some significant interactions with drugs frequently used in cancer patients, which might influence their pharmacokinetics, compromising their efficacy and safety. In the present review, we analyzed the available data from the subgroups of patients with active cancer who were included in Phase III clinical trials that assessed the efficacy and safety of NOACs in the prevention and treatment of VTE. The data from the Phase III trials in prophylaxis of VTE by rivaroxaban or apixaban highlight that these two agents, although belonging to the same pharmacological group (direct inhibitors of factor Xa), have substantially different profiles of efficacy and safety, especially in hospitalized acutely ill medical patients with active cancer. A limited number of patients with VTE and active

  6. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness

    PubMed Central

    Mani, Helen; Lindhoff-Last, Edelgard

    2014-01-01

    Atrial fibrillation (AF) continues to be a leading cause of cerebrovascular morbidity and mortality resulting from cardioembolic stroke. Oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by more than 50%. Appropriate use of anticoagulation with vitamin K antagonists requires precise adherence and monitoring. A number of factors that potentially induce patients’ dissatisfaction reduce quality of patient life. New direct oral anticoagulants, such as the direct factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the thrombin inhibitor dabigatran, were developed to overcome the limitations of the conventional anticoagulant drugs. However, models to optimize the benefit of therapy and to ensure that therapy can be safely continued are missing for the new oral anticoagulants. This review will briefly describe the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban with focus on their use for prevention of embolic events in AF. Moreover, it will discuss the safety, efficacy, cost data, and benefit for patients’ quality of life and adherence. PMID:24970997

  7. A real world data of dabigatran etexilate: multicenter registry of oral anticoagulants in nonvalvular atrial fibrillation.

    PubMed

    Yavuz, Bunyamin; Ayturk, Mehmet; Ozkan, Selcuk; Ozturk, Mujgan; Topaloglu, Caner; Aksoy, Hakan; Şabanoglu, Cengiz; Tanalp, Ali Cevat; Dal, Kursat; Ata, Naim; Yavuz, Burcu Balam

    2016-10-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia. Dabigatran etixalate (DE) is one of the new oral anticoagulant drugs being used in nonvalvular AF (NVAF). There is no adequate real world data in different populations about DE. The aim of this registry was to evaluate the efficacy and safety of DE Consecutive NVAF patients treated with warfarin or both DE doses were enrolled during 18 months study period. The patients were re-evaluated at regular 6-month intervals during the follow-up period. During the follow-up period outcomes were documented according to RELY methodology A total of 555 patients were analyzed. There was no significant difference in ischemic stroke rates (p = 0.73), death rates (p = 0.15) and MI rates (p = 0.56) between groups. The rate of major bleeding was significantly higher in warfarin and dabigatran 150 mg group than dabigatran 110 mg (p < 0.001). Intracranial bleeding rate and relative risk were significantly lower in dabigatran 110 mg group than warfarin group (p = 0.004). Dyspepsia was significantly higher in both DE doses than warfarin (p = 0.004) Both DE doses are as effective as warfarin in reducing stroke rates in NVAF patients, without increasing MI rates. Intracranial bleeding rates are significantly lower in warfarin than both doses of DE and gastrointestinal bleeding risk increases with increased DE doses.

  8. New Oral Anticoagulants May Be Particularly Useful for Asian Stroke Patients

    PubMed Central

    Bang, Oh Young; Hong, Keun-Sik; Heo, Ji Hoe; Koo, Jaseong; Kwon, Sun U.; Yu, Kyung-Ho; Bae, Hee-Joon; Lee, Byung-Chul; Yoon, Byung-Woo

    2014-01-01

    Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in

  9. Suboptimal use of non-vitamin K antagonist oral anticoagulants: Results from the RAMSES study.

    PubMed

    Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Cağri; Kalaycioğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalcik, Macit; Yaman, Mehmet; İnci, Sinan; Altintaş, Bernas; Kalkan, Sedat; Kirma, Cevat; Biteker, Murat

    2016-08-01

    This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians' adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study).RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression.Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3.The suboptimal use of NOACs is common because of physicians' poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients. PMID:27583892

  10. Patients' perspectives on self-testing of oral anticoagulation therapy: Content analysis of patients' internet blogs

    PubMed Central

    2011-01-01

    Background Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Methods Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. Results The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Conclusions Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum

  11. Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes

    PubMed Central

    2010-01-01

    Background Stroke incidence increases with age. Atrial fibrillation (AF) is an important risk factor for ischemic stroke and its incidence also increases with age. However oral anticoagulant therapy (OAT) tends to be underused in the elderly population. Methods Elderly patients (> = 80 years) with an ischemic stroke admitted in our department between 1/7/2003 and 31/6/2005 were prospectively evaluated. Baseline characteristics, risk factors, treatment and etiology according to TOAST criteria were recorded. Patients treated with OAT were followed up in order to assess any side effect and stroke recurrence. Mean follow-up was of 19.5 months (7-45) from discharge. Results Sixty four out of a hundred and fifty nine elderly patients (40.25%) were classified as cardioembolic; mean age was 84.5 years (80-97) and 64.6% were women. AF had been previously identified in 60% of them (16.9% were on OAT and 40.6% on antiplatelet therapy). At discharge, 32 patients (49.2%) were on OAT. In the follow-up 4 patients (12.5%) suffered systemic haemorrhages (3 urinary, 1 gastrointestinal bleeding), with no change in their functional status. Mean INR in this group was 5.9 [3-11] and, in 3 of them, OAT was cancelled. No brain haemorrhages were recorded. Ischemic stroke recurred in 4 patients (INR < 1.8 in 3 of them; the other, INR 2.35). Three patients had died at the end of the follow-up, one of them as a consequence of ischemic stroke recurrence. Discussion Twenty eight point eight of stroke patients admitted in the period of study were >80 years. The high proportion of cardioembolic strokes in this age segment contrasts with the general underuse of OAT as antithrombotic prophylaxis. Our study suggests that OAT is a safe strategy when carefully prescribed, even for elderly patients. PMID:20525389

  12. Novel oral anticoagulants for the secondary prevention of cerebral ischemia: a network meta-analysis

    PubMed Central

    Katsanos, Aristeidis H.; Mavridis, Dimitris; Parissis, John; Deftereos, Spyridon; Frogoudaki, Alexandra; Vrettou, Agathi-Rosa; Ikonomidis, Ignatios; Chondrogianni, Maria; Safouris, Apostolos; Filippatou, Angeliki; Voumvourakis, Konstantinos; Triantafyllou, Nikos; Ellul, John; Karapanayiotides, Theodore; Giannopoulos, Sotirios; Alexandrov, Anne W.; Alexandrov, Andrei V.; Tsivgoulis, Georgios

    2016-01-01

    Background: Novel oral anticoagulants (NOACs) have shown to be both safe and effective for ischemic stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). We conducted a network meta-analysis (NMA) using published data from secondary prevention subgroups of different phase III randomized clinical trials (RCTs) comparing individual NOACs with warfarin. Methods: Eligible studies were identified by searching MEDLINE and SCOPUS and the Cochrane Central Register of Controlled Trials databases. First, we conducted a pairwise meta-analysis for each pairwise comparison, and then we performed NMA to combine direct and indirect evidence for any given pair of treatments. The comparative effects of all NOACs against warfarin were ranked with the surface under the cumulative ranking (SUCRA) curve for each outcome. Results: We identified four RCTs (including 15,240 patients) comparing individual NOACs (apixaban, dabigatran, rivaroxaban) with warfarin. Using indirect evidence, dabigatran was related to a significantly lower risk of hemorrhagic stroke compared with rivaroxaban [risk ratio (RR) 0.28; 95% confidence interval (CI) 0.11–0.75], while rivaroxaban was associated with a significantly lower risk of major gastrointestinal bleeding compared with dabigatran (RR 0.14; 95% CI 0.03–0.74). We also performed clustered ranking plot for the primary efficacy and safety endpoints to identify the treatment with the probably best benefit-to-risk ratio profile. Conclusions: The three NOACs showed differences in terms of safety and efficacy for secondary stroke prevention in NVAF. Our findings can serve only as hypothesis generation and require independent confirmation in head-to-head RCTs, owing to the sparse available evidence and increased uncertainty in both indirect effect estimates and ranking of treatments. PMID:27582891

  13. Early introduction of direct oral anticoagulants in cardioembolic stroke patients with non-valvular atrial fibrillation.

    PubMed

    Cappellari, Manuel; Carletti, Monica; Danese, Alessandra; Bovi, Paolo

    2016-10-01

    Direct oral anticoagulants (DOACs) are superior to warfarin in reduction of the intracranial bleeding risk. The aim of the present study was to assess whether early DOAC introduction (1-3 days after onset) in stroke patients with non-valvular atrial fibrillation (nVAF) may be safe and effective, compared with DOAC introduction after 4-7 days. We conducted a prospective analysis based on data collected from 147 consecutive nVAF patients who started DOAC within 7 days after stroke onset. In all patients, we performed pre-DOAC CT scan 24-36 h after onset and follow-up CT scan at 7 days after DOAC introduction. Outcome measures were post-DOAC intracranial bleeding (new any intracerebral hemorrhage (ICH) in patients with pre-DOAC infarct without hemorrhagic transformation (HT) or expansion of ICH in patients with pre-DOAC infarct with asymptomatic HT) and post-DOAC recurrent ischemic stroke (any new ischemic infarct) on follow-up CT scan. 97 patients started DOAC after 1-3 days and 50 patients started DOAC after 4-7 days. On pre-DOAC CT scan, 132 patients had an infarct without HT and 15 an infarct with asymptomatic HT. On follow-up CT scan, new any ICH was noted in seven patients (asymptomatic in 6) and asymptomatic expansion of ICH in one patient. We found no association between early DOAC introduction and intracranial bleeding. Large infarct remained the only independent predictor of post-DOAC intracranial bleeding. No patients suffered recurrent ischemic stroke after DOAC introduction. Early DOAC introduction might be safe in carefully selected patients with nVAF who experience small- and medium-sized cardioembolic ischemic strokes. Further investigation will be needed. PMID:27329483

  14. The Prototype Compound for the Oral Anticoagulants: 3,3'-Methylene bis(4-hydroxycoumarin).

    ERIC Educational Resources Information Center

    Hayward, Rodney C.

    1984-01-01

    Provides background information on the development and action of the coumarin family of anticoagulants, focusing on an experimental procedure for the synthesis of dicumerol. Includes procedures used and safety considerations. (JM)

  15. [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.

  16. Economic evaluation of the use of point-of-care devices in patients with long term oral anticoagulation.

    PubMed

    Gerkens, Sophie; Gailly, Jeannine; Obyn, Caroline; Devriese, Stephan; Cleemput, Irina

    2012-10-01

    To examine the cost and cost-effectiveness of the use of point-of-care (POC) devices by the general practitioner (GP), in anticoagulation clinic or by the patient in self-testing (PST) and self-management (PSM), compared with standard laboratory testing to realize international normalized ratio tests for patients on long term anticoagulation therapy. An economic evaluation was performed from the Belgian health care payer's perspective using a Markov model. Outcomes data were derived from a meta-analysis and cost data were derived from claims databases. Several scenarios were tested based on number of tests and GP's contacts and probabilistic sensitivity analysis was used to handle uncertainty. Evidence on the impact of POC on mortality was only found for PSM. Therefore, a cost-effectiveness analysis was performed for PSM and for other strategies, only a cost comparison was done. With an unchanged number of tests, POC is cost-saving compared to laboratory testing (probability > 70%). In scenarios where POC induces more tests, results were different: with 52 tests/year, only PSM kept a probability of remaining cost-saving superior to 50%. Except in the case of 100% of GP consultations maintained and 52 tests/year performed, PSM resulted in significantly more "life years gained" (LYG) than usual care and was on average cost-saving. The organisation of long term oral anticoagulation monitoring should be directed towards PSM and, to a lesser extent, PST for selected and trained patients. PMID:22437654

  17. 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.

  18. Direct oral anticoagulants in atrial fibrillation: can data from randomized clinical trials be safely transferred to the general population? No.

    PubMed

    Marietta, Marco

    2015-09-01

    Direct oral anticoagulants (DOAC) represent an innovative and relevant treatment for the prevention of cardiac embolism in patients with atrial fibrillation (AF). Their introduction has been followed by an ample debate on their appropriate use, considering that they can offer an effective treatment for the many patients with AF, which are not taking any effective anticoagulant treatment, even though they have a substantial thromboembolic risk (1). On the other hand, DOAC are much less tested in everyday clinical practice and much more expensive than anti-vitamin k anticoagulants (AVKs). Starting from the quite favorable results of the available randomized controlled trials (RCTs)--showing that DOAC are at least non-inferior to AVK and that may be even better for some outcomes--this article discusses their transferability to the majority of AF patients. In summary, the body of evidence supports the efficacy and safety of DOAC in patients carrying demographic and clinical characteristics similar to subjects included in RCT, but their use in less well-characterized subpopulations requires particular caution, while waiting for more reliable data from the real world.

  19. New anticoagulants.

    PubMed

    Weitz, J I; Bates, S M

    2005-08-01

    The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. Novel parenteral agents include synthetic analogs of the pentasaccharide sequence of heparin that mediates its interaction with antithrombin. Fondaparinux, the first synthetic pentasaccharide, is licensed for prevention of venous thromboembolism (VTE) after major orthopedic surgery and for initial treatment of patients with VTE. Idraparinux, a long-acting pentasaccharide that is administered subcutaneously once-weekly, is being compared with warfarin for treatment of VTE and for prevention of cardioembolic events in patients with atrial fibrillation. New oral anticoagulants include direct inhibitors of thrombin, factor Xa and factor IXa. Designed to provide more streamlined anticoagulation than warfarin, these agents can be given without routine coagulation monitoring. Ximelagatran, the first oral direct thrombin inhibitor, is as effective and safe as warfarin for prevention of cardioembolic events in patients with atrial fibrillation. However, ximelagatran produces a three-fold elevation in alanine transaminase levels in 7.9% of patients treated for more than a month, the long-term significance of which is uncertain. Whether other direct thrombin inhibitors or inhibitors of factors Xa or IXa also have this problem is under investigation. After a brief review of coagulation pathways, this paper focuses on new anticoagulants in advanced stages of clinical testing. PMID:16102051

  20. Epidemiology of Intracranial Haemorrhages Associated with Vitamin K Antagonist Oral Anticoagulants in Spain: TAC Registry

    PubMed Central

    Zapata-Wainberg, Gustavo; Ximénez-Carrillo Rico, Álvaro; Benavente Fernández, Lorena; Masjuan Vallejo, Jaime; Gállego Culleré, Jaime; Freijó Guerrero, María del Mar; Egido, José; Gómez Sánchez, José Carlos; Martínez Domeño, Alejandro; Purroy García, Francisco; Vives Pastor, Bárbara; Blanco González, Miguel; Vivancos, José

    2015-01-01

    Background Vitamin K antagonist oral anticoagulants (VKA-OACs) are effective for primary and secondary prevention of embolic events. The rate of haemorrhagic neurological complications in patients admitted to neurology departments in Spain is not yet known. Aims We aimed to determine the clinical and epidemiological characteristics of patients with intracranial haemorrhage secondary to VKA-OACs as well as the incidence of this severe complication. Methods We conducted a retrospective, descriptive, multi-centre study using information from the medical records of all patients admitted to neurology departments, diagnosed with spontaneous intracranial haemorrhage, and treated with VKA-OACs within a 1-year period. We collected demographic and care data from centres, patients' medical records [demographic data, medical history, haemorrhage origin, vascular risk factors, concomitant treatment, and National Institutes of Health Stroke Scale (NIHSS) scores], and patients' outcome at 3 months [independence (modified Rankin Scale score <3) and mortality rate]. Results Twenty-one hospitals serving a population of 8,155,628 inhabitants participated in the study. The total number of cases was 235, the mean age was 78.2 (SD 9.4) years, and the baseline NIHSS score was 11.6 (SD 9.5; median 9; interquartile range 14). The VKA-OACs used were acenocoumarol in 95.3% (224 patients) and warfarin in 4.7% (11 patients). The haemorrhage origin was deep in 29.8%, lobar in 25.5%, intraventricular in 11.5%, extensive in 17.4% (>100 ml), cerebellar in 12.3%, and in the brainstem in 3.4%. The international normalised ratio was within therapeutic ranges at admission (according to indication) in 29.4% (69 patients). The global incidence (cases per 100,000 inhabitants per year) is 2.88. The in-hospital mortality rate was 40%, and 24.3% of the patients were independent at 3 months, while the mortality at 3 months was 42.6%. Conclusion VKA-OAC treatment is associated with a large percentage of all

  1. Consistency of Safety and Efficacy of New Oral Anticoagulants across Subgroups of Patients with Atrial Fibrillation

    PubMed Central

    Gremillet, Cyrielle; Chapelle, Céline; Mismetti, Patrick; Cucherat, Michel; Vital-Durand, Denis; Laporte, Silvy

    2014-01-01

    Aims The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure. Methods and Results All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67–0.86]) than in those with heart failure (RR = 0.90 [0.78–1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0–1 (RR 0.67 CI 0.57–0.79) than in those with a score ≥2 (RR 0.85 CI 0.74–0.98). Comparison of MB in patients with (RR 0.97 CI 0.79–1.18) and without (RR 0.76 CI 0.65–0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction. Conclusions NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction. PMID:24622012

  2. 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

  3. 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

  4. 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.

  5. A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

    PubMed Central

    Chang, Jeremy B.; Quinnies, Kayla M.; Realubit, Ronald; Karan, Charles; Rand, Jacob H.; Tatonetti, Nicholas P.

    2016-01-01

    A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7 ± 0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5 ± 1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. PMID:27439480

  6. Rationale and design of the ODIn-AF Trial: randomized evaluation of the prevention of silent cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation.

    PubMed

    Schrickel, Jan W; Linhart, Markus; Bänsch, Dietmar; Thomas, Daniel; Nickenig, Georg

    2016-02-01

    Oral anticoagulation treatment following clinically successful catheter ablation of atrial fibrillation is controversial. Recent guidelines recommend continuation of oral anticoagulation in all patients with CHA2DS2VASc score ≥ 2 even if there is no evidence of recurrent atrial fibrillation. Due to lack of prospective data, the net clinical benefit of oral anticoagulation after successful ablation in these patients is unclear. As oral anticoagulation bears the risk of severe bleeding events, the ODIn-AF study aims to evaluate the effect of oral anticoagulation on the incidence of silent cerebral embolic events in patients with a high risk for embolic events, but free from symptomatic atrial fibrillation after successful pulmonary vein ablation. PMID:26514352

  7. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

    PubMed Central

    Kline, Jeffrey A; Kahler, Zachary P; Beam, Daren M

    2016-01-01

    Background Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE) in outpatients. Objectives The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. Methods Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms questionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]). The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT) to those with pulmonary embolism (PE). Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. Results From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/253 patients had recurrent DVT and 2/253 had major hemorrhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively) and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively), consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians’ (N=116) before-to-after protocol comfort level with home treatment of PE increased 48% on visual analog scale. Conclusion Hestia-negative VTE patients treated with oral monotherapy at home had low rates of VTE recurrence and bleeding, as well as quality of life measurements similar to prior reports. PMID:27143861

  8. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines

    PubMed Central

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-01-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. Direct Oral Anticoagulants (DOAC) For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30–50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26873868

  9. Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors.

    PubMed

    Beyer, Jacob; Trujillo, Toby; Fisher, Sheila; Ko, Ann; Lind, Stuart E; Kiser, Tyree H

    2016-07-01

    The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations.

  10. Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Patel, Priyesh A.; Zhao, Xin; Fonarow, Gregg C.; Lytle, Barbara L.; Smith, Eric E.; Xian, Ying; Bhatt, Deepak L.; Peterson, Eric D.; Schwamm, Lee H.; Hernandez, Adrian F.

    2015-01-01

    Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized. Methods and Results Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc). Conclusions NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin. PMID:26058721

  11. Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism. A propensity-matched cohort study.

    PubMed

    Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker

    2016-08-30

    Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency. PMID:27412804

  12. Do novel oral anticoagulants do better than standard therapy in the treatment of deep vein thrombosis?

    PubMed

    Brodmann, M

    2013-08-01

    The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor. PMID:23681109

  13. The Indian consensus guidance on stroke prevention in atrial fibrillation: An emphasis on practical use of nonvitamin K oral anticoagulants.

    PubMed

    Dalal, Jamshed; Bhave, Abhay; Oomman, Abraham; Vora, Amit; Saxena, Anil; Kahali, Dhiman; Poncha, Fali; Gambhir, D S; Chaudhuri, Jaydip Ray; Sinha, Nakul; Ray, Saumitra; Iyengar, S S; Banerjee, Suvro; Kaul, Upendra

    2015-12-01

    The last ten years have seen rapid strides in the evolution of nonvitamin K oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). For the preparation of this consensus, a comprehensive literature search was performed and data on available trials, subpopulation analyses, and case reports were analyzed. This Indian consensus document intends to provide guidance on selecting the right NOAC for the right patients by formulating expert opinions based on the available trials and Asian/Indian subpopulation analyses of these trials. A section has been dedicated to the current evidence of NOACs in the Asian population. Practical suggestions have been formulated in the following clinical situations: (i) Dose recommendations of the NOACs in different clinical scenarios; (ii) NOACs in patients with rheumatic heart disease (RHD); (iii) Monitoring anticoagulant effect of the NOACs; (iv) Overdose of NOACs; (v) Antidotes to NOACs; (vi) Treatment of hypertrophic cardiomyopathy (HCM) with AF using NOACs; (vii) NOACs dose in elderly, (viii) Switching between NOACs and vitamin K antagonists (VKA); (ix) Cardioversion or ablation in NOAC-treated patients; (x) Planned/emergency surgical interventions in patients currently on NOACs; (xi) Management of bleeding complications of NOACs; (xii) Management of acute coronary syndrome (ACS) in AF with NOACs; (xiii) Management of acute ischemic stroke while on NOACs.

  14. 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

  15. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs)

    PubMed Central

    van Gorp, Rick H.; Schurgers, Leon J.

    2015-01-01

    Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction. PMID:26593943

  16. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs).

    PubMed

    van Gorp, Rick H; Schurgers, Leon J

    2015-11-17

    Vitamin K-antagonists (VKA) are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC) drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs). As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

  17. [The use of the new direct oral anticoagulants among older subjects: The limits of the evidence-based medicine?].

    PubMed

    Vogel, T; Lang, P-O; Kaltenbach, G; Karcher, P

    2015-12-01

    The growing use of direct oral anticoagulants, in particular among older subjects, raises questions about the limits of the evidence-based medicine. The phase III studies that have validated the efficacy and the safety profile of these molecules (dabigatran, rivaroxaban, apixaban, edoxaban) in their both indications, the venous thromboembolic disease and the non-valvular atrial fibrillation raise concerns in four major fields: the financial support of pharmaceutical companies, the links of interest for many authors with the industry, the study design (exclusively non-inferiority studies), and the poor representativeness of the older subjects included. All these points are discussed, using data of sub-groups studies, post-marketing studies and recent meta-analysis. The lack of data for the very old subjects, with frailty or comorbidities, remains the main concern from these phase III studies.

  18. Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: beyond bleeding complications.

    PubMed

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

    2016-08-25

    Non-vitamin K oral anticoagulants, also known as direct oral anticoagulants (DOACs), have entered the market in 2008 with the expected breakthrough potential of circumventing limitations related to treatment with vitamin K antagonists (eg, warfarin) by virtue of their pharmacological properties. Although data derived from premarketing randomized clinical trials have largely demonstrated the clinical benefit of DOACs, especially in terms of reduced risk of intracranial bleeding, it is important to monitor the safety in the postmarketing phase, which better reflects real-world patients with comorbidities and polypharmacotherapy, in order to assess the actual risk-benefit profile. In this critical review, we aimed to evaluate the evidence on the latest debated safety issues. In the first section, we will discuss: 1) the need for pharmacovigilance (ie, the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems in the real-world setting), and 2) the importance of properly interpreting postmarketing data to avoid unnecessary alarm. In the second section, emerging and debated safety issues potentially associated with the use of DOACs in the postmarketing setting will be assessed: 1) the potential coronary risk (which emerged during the preapproval period); 2) the occurrence of liver injury (a risk undetected in clinical trials and highlighted by case reports or series); and 3) the potential for renal damage (a still unclear safety issue). It is anticipated that hepatic and renal issues still require dedicated postauthorization safety studies to ultimately assess causality. PMID:27578223

  19. The optimal management of patients on oral anticoagulation undergoing coronary artery stenting. The 10th Anniversary Overview.

    PubMed

    Rubboli, A; Faxon, D P; Juhani Airaksinen, K E; Schlitt, A; Marín, F; Bhatt, D L; Lip, G Y H

    2014-12-01

    Even 10 years after the first appearance in the literature of articles reporting on the management of patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention with stent (PCI-S), this issue is still controversial. Nonetheless, some guidance for the everyday management of this patient subset, accounting for about 5-8 % of all patients referred for PCI-S, has been developed. In general, a period of triple therapy (TT) of OAC, with either vitamin K-antagonists (VKA) or non-vitamin K-antagonist oral anticoagulants (NOAC), aspirin, and clopidogrel is warranted, followed by the combination of OAC, and a single antiplatelet agent for up to 12 months, and then OAC alone. The duration of the initial period of TT is dependent on the individual risk of thromboembolism, and bleeding, as well as the clinical context in which PCI-S is performed (elective vs acute coronary syndrome), and the type of stent implanted (bare-metal vs drug-eluting). In this article, we aim to provide a comprehensive, at-a-glance, overview of the management strategies, which are currently suggested for the peri-procedural, medium-term, and long-term periods following PCI-S in OAC patients. While acknowledging that most of the evidence has been obtained from patients on OAC because of atrial fibrillation, and with warfarin being the most frequently used VKA, we refer in this overview to the whole population of OAC patients undergoing PCI-S. We refer to the whole population of patients on OAC undergoing PCI-S also when OAC is carried out with NOAC rather than VKA, pointing out, when appropriate, the particular management issues.

  20. Pharmacokinetics of the amidine prodrug of a novel oral anticoagulant factor VIIa inhibitor (AS1924269-00) in rats.

    PubMed

    Nakabayashi, T; Gotoh, Y; Kamada, N; Fujioka, M; Ishihara, T; Hirabayashi, A; Sato, H

    2013-05-01

    AS1924269-00 is a promising orally applicable anticoagulant that inhibits FVIIa but has very low oral absorption. Therefore, in this study, we aimed to develop a prodrug of AS1924269-00, which possesses a carbamate-added amidine functional group, with high membrane permeability. We investigated the pharmacokinetics of the carbamate-type prodrug of AS1924269-00 in rats. The Caco-2 cell monolayer was used as an in vitro model and in parallel an artificial membrane permeability assay (PAMPA) was performed to examine the transport mechanisms of the prodrug. The bioavailability of the active form was determined to be only 0.3% in rats, but the oral absorption of the prodrug was markedly improved, and its bioavailability was 36%. Our in vivo result was consistent with the finding that compared to AS1924269-00, the prodrug showed favorable permeability in Caco-2 cells and PAMPA. We introduced carbamate into the amidine functional group of the FVIIa inhibitor, which possesses the amidine backbone, and converted it to a prodrug using carboxylic acid ethyl ester. This novel prodrug had favorable absorption and membrane permeability in vivo and in vitro. Thus, we suggest a clinical application of the carbamate-added amidine prodrug of the FVIIa inhibitor. PMID:23802432

  1. Discrepancies between Patients’ Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations

    PubMed Central

    Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

    2016-01-01

    Background 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. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods 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. Results 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. Conclusion 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

  2. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia.

    PubMed

    Hernández-Boluda, Juan-Carlos; Arellano-Rodrigo, Eduardo; Cervantes, Francisco; Alvarez-Larrán, Alberto; Gómez, Montse; Barba, Pere; Mata, María-Isabel; González-Porras, José-Ramón; Ferrer-Marín, Francisca; García-Gutiérrez, Valentín; Magro, Elena; Moreno, Melania; Kerguelen, Ana; Pérez-Encinas, Manuel; Estrada, Natàlia; Ayala, Rosa; Besses, Carles; Pereira, Arturo

    2015-06-01

    It is unclear whether anticoagulation guidelines intended for the general population are applicable to patients with polycythemia vera (PV) and essential thrombocythemia (ET). In the present study, the risk of thrombotic recurrence was analyzed in 150 patients with PV and ET treated with vitamin K antagonists (VKA) because of an arterial or venous thrombosis. After an observation period of 963 patient-years, the incidence of re-thrombosis was 4.5 and 12 per 100 patient-years under VKA therapy and after stopping it, respectively (P < 0.0005). After a multivariate adjustment for other prognostic factors, VKA treatment was associated with a 2.8-fold reduction in the risk of thrombotic recurrence. Notably, VKA therapy offset the increased risk of re-thrombosis associated with a prior history of remote thrombosis. Both the protective effect of VKA therapy and the predisposing factors for recurrence were independent of the anatomical site involved in the index thrombosis. Treatment periods with VKA did not result in a higher incidence of major bleeding as compared with those without VKA. These findings support the use of long-term anticoagulation for the secondary prevention of thrombosis in patients with PV and ET, particularly in those with history of remote thrombosis.

  3. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.

    PubMed

    Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B

    2014-09-01

    Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. PMID:25173533

  4. Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients.

    PubMed

    Zuchinali, Priccila; Souza, Gabriela C; Aliti, Graziella; Botton, Mariana R; Goldraich, Lívia; Santos, Katia G; Hutz, Mara H; Bandinelli, Eliane; Rohde, Luis E

    2014-04-01

    Significant inter-individual variability on the effect of vitamin K to reverse overanticoagulation has been identified. Genetic polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene might explain in part this variability. The objective of this study was to evaluate the influence of VKORC1 -1639G>A and 3730G>A polymorphisms on the effect of oral vitamin K supplementation in overanticoagulated patients. We performed an interventional trial of oral vitamin K supplementation in over-anticoagulated outpatients (international normalized ratio [INR] ≥ 4). Subjects received vitamin K (2.5-5.0 mg) according to baseline INR and were genotyped by real time polymerase chain reaction (PCR). INR values were determined at 3, 6, 24 and 72 h after supplementation. We evaluated 33 outpatients, 61 % were males, with a mean age of 62 ± 12 years old. There was a significant decrease in INR values over time for both polymorphisms after oral vitamin K. At 3 h after supplementation, patients carrying the G allele for the -1639G>A polymorphism had a greater decrease in INR values compared to AA patients (p < 0.05 for difference among groups; p < 0.001 for time variation; p = 0.001 for time × group interaction), with differences of -1.01 for GG versus AA (p = 0.003) and -0.84 for GA versus AA (p = 0.024). Mean INR value at 24 h was 1.9 ± 0.6 and at 72 h was 2.1 ± 0.7, with no differences among genotypes. No significant interaction was identified between the 3730G>A polymorphism and vitamin K supplementation. Our study indicated that the VKORC1 -1639G>A polymorphism plays a role in the response to acute vitamin K supplementation in over-anticoagulated patients, with faster decrease of INR value in patients carrying the G allele.

  5. Evaluation of factors affecting gastrointestinal absorption of a novel anticoagulant FX-93 for development of oral formulation.

    PubMed

    Takemura, Shigeo; Kondo, Hiromu; Suzumura, Kenichi; Ogawara, Ken-Ichi; Watanabe, Shunsuke; Sako, Kazuhiro; Higaki, Kazutaka

    2012-06-01

    To find out factors causing the low bioavailability of FX-93, a novel anticoagulant, its solubility, membrane permeability, and the effect of bile salt on the absorption of FX-93 were investigated. The solubility of FX-93 under physiological conditions ranged from 0.3 to 18.3 mg/mL and the dose number was calculated to be 0.02-0.27, suggesting that the intrinsic solubility of FX-93 should not be a limiting factor for oral absorption. Apparent permeability of FX-93 across Caco-2 cell monolayer suggested that its fraction of dose absorbed would range between 30% and 40% in humans. Furthermore, FX-93 was substantially absorbed from each segment of rat intestine. However, the decrease in the gastrointestinal transit rate significantly decreased maximum plasma concentration and area under the plasma concentration-time curve of FX-93 after oral dosing in dogs, suggesting that FX-93 absorption would be suppressed by some components in the small intestinal lumen. An in situ rat administration study indicated that bile significantly decreased the intestinal absorption of FX-93 by two-thirds, which could be attributed to the decrease in FX-93 solubility by the interaction with bile or bile acid. Nuclear magnetic resonance spectroscopy analysis suggested that FX-93 would interact with bile salt between the naphthalene ring of FX-93 and steroidal backbone of bile salt. PMID:22422596

  6. Prestroke Antiplatelet Effect on Symptomatic Intracranial Hemorrhage and Functional Outcome in Intravenous Thrombolysis

    PubMed Central

    Choi, Jay Chol; Lee, Ji Sung; Park, Tai Hwan; Cho, Yong-Jin; Park, Jong-Moo; Kang, Kyusik; Lee, Kyung Bok; Lee, Soo Joo; Kim, Jae Guk; Lee, Jun; Park, Man-Seok; Choi, Kang-Ho; Kim, Joon-Tae; Yu, Kyung-Ho; Lee, Byung-Chul; Oh, Mi-Sun; Cha, Jae-Kwan; Kim, Dae-Hyun; Nah, Hyun-Wook; Kim, Dong-Eog; Ryu, Wi-Sun; Kim, Beom Joon; Bae, Hee-Joon; Kim, Wook-Joo; Shin, Dong-Ick; Yeo, Min-Ju; Sohn, Sung Il; Hong, Jeong-Ho; Lee, Juneyoung; Hong, Keun-Sik

    2016-01-01

    Background and Purpose About 30%-40% of stroke patients are taking antiplatelet at the time of their strokes, which might increase the risk of symptomatic intracranial hemorrhage (SICH) with intravenous tissue plasminogen activator (IV-TPA) therapy. We aimed to assess the effect of prestroke antiplatelet on the SICH risk and functional outcome in Koreans treated with IV-TPA. Methods From a prospective stroke registry, we identified patients treated with IV-TPA between October 2009 and November 2014. Prestroke antiplatelet use was defined as taking antiplatelet within 7 days before the stroke onset. The primary outcome was SICH. Secondary outcomes were discharge modified Rankin Scale (mRS) score and in-hospital mortality. Results Of 1,715 patients treated with IV-TPA, 441 (25.7%) were on prestroke antiplatelet. Prestroke antiplatelet users versus non-users were more likely to be older, to have multiple vascular risk factors. Prestroke antiplatelet use was associated with an increased risk of SICH (5.9% vs. 3.0%; adjusted odds ratio [OR] 1.79 [1.05-3.04]). However, at discharge, the two groups did not differ in mRS distribution (adjusted OR 0.90 [0.72-1.14]), mRS 0-1 outcome (34.2% vs. 33.7%; adjusted OR 1.27 [0.94-1.72), mRS 0-2 outcome (52.4% vs. 52.9%; adjusted OR 1.21 [0.90-1.63]), and in-hospital mortality (6.1% vs. 4.2%; adjusted OR 1.19 [0.71-2.01]). Conclusions Despite an increased risk of SICH, prestroke antiplatelet users compared to non-users had comparable functional outcomes and in-hospital mortality with IV-TPA therapy. Our results support the use of IV-TPA in eligible patients taking antiplatelet therapy before their stroke onset. PMID:27733024

  7. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients’ experiences

    PubMed Central

    Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison

    2015-01-01

    Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266

  8. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

    PubMed Central

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F.; Hamaoka, Takafumi

    2015-01-01

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously. PMID:26109079

  9. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

    PubMed

    Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

    2015-06-25

    Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

  10. A novel prothrombin time assay for assessing the anticoagulant activity of oral factor Xa inhibitors.

    PubMed

    Barrett, Yu Chen; Wang, Zhaoqing; Knabb, Robert M

    2013-09-01

    Conventional prothrombin time (PT) assays have limited sensitivity and dynamic range in monitoring the anticoagulant activity of direct factor Xa inhibitors. Hence, new assays are needed. We modified a PT assay by adding calcium chloride (CaCl2) to the thromboplastin reagent to increase assay dynamic range and improve sensitivity. Effects of calcium and sodium ion concentrations, and sample handling, were evaluated to optimize assay performance. Increasing concentrations of calcium ions produced progressive increases in PT across the factor Xa inhibitor concentrations of 0 to 2500 nmol/L for razaxaban and apixaban. The greatest effect was seen when the thromboplastin reagent was diluted 1:2.25 with 100 mmol/L CaCl2 (thus selected for routine use). The optimized assay showed an interassay precision of 1.5 to 9.3 percentage coefficient of variation (%CV) for razaxaban and 3.1 to 4.6 %CV for apixaban. We conclude that the modified PT assay is likely to be suitable as a pharmacodynamic marker for activity at therapeutic concentrations of factor Xa inhibitors.

  11. New Prospective for the Management of Low-Risk Pulmonary Embolism: Prognostic Assessment, Early Discharge, and Single-Drug Therapy with New Oral Anticoagulants

    PubMed Central

    2012-01-01

    Patients with pulmonary embolism (PE) can be stratified into two different prognostic categories, based on the presence or absence of shock or sustained arterial hypotension. Some patients with normotensive PE have a low risk of early mortality, defined as <1% at 30 days or during hospital stay. In this paper, we will discuss the new prospective for the optimal management of low-risk PE: prognostic assessment, early discharge, and single-drug therapy with new oral anticoagulants. Several parameters have been proposed and investigated to identify low-risk PE: clinical prediction rules, imaging tests, and laboratory markers of right ventricular dysfunction or injury. Moreover, outpatient management has been suggested for low-risk PE: it may lead to a decrease in unnecessary hospitalizations, acquired infections, death, and costs and to an improvement in health-related quality of life. Finally, the main characteristics of new oral anticoagulant drugs and the most recent published data on phase III trials on PE suggest that the single-drug therapy is a possible suitable option. Oral administration, predictable anticoagulant responses, and few drug-drug interactions of direct thrombin and factor Xa inhibitors may further simplify PE home therapy avoiding administration of low-molecular-weight heparin. PMID:24278706

  12. Comparison of the anticoagulant and antithrombotic effects of YM-75466, a novel orally-active factor Xa inhibitor, and warfarin in mice.

    PubMed

    Sato, K; Taniuchi, Y; Kawasaki, T; Hirayama, F; Koshio, H; Matsumoto, Y; Iizumi, Y

    1998-10-01

    The anticoagulant and antithrombotic effects of YM-75466 (N-[4-[(1-acetimidoyl-4-piperidyl)oxy]phenyl]-N-[(7-amidino-2-naph thyl)methyl]sulfamoyl acetic acid monomethanesulfonate), a novel orally-active factor Xa (FXa) inhibitor, and warfarin were compared in mice. Both agents were orally administered in all studies. In ex vivo studies, the peak effects of YM-75466 occurred 1 hr after administration while the peak of warfarin activity occurred 18 hr after administration. At each peak, both YM-75466 and warfarin prolonged coagulation time dose-dependently. The dose response curve of warfarin for prothrombin time was steeper than that of YM-75466. In a thromboplastin-induced thromboembolism model, administration of 30 mg/kg YM-75466 or 3 mg/kg warfarin significantly improved the lethality ratio. In blood loss studies, YM-75466 did not increase blood loss from the tail even at 30 mg/kg, while warfarin markedly increased blood loss at 3 mg/kg. Agents that interfere with warfarin action did not interfere with YM-75466 action. In conclusion, this study shows that YM-75466 has advantages over warfarin: i) rapid onset of anticoagulant activity, ii) wide therapeutic range, iii) little effect on bleeding and iv) lack of drug interaction with agents that interfere with warfarin. These results suggest that YM-75466 may be promising as a novel oral anticoagulant agent. PMID:9829622

  13. Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.

    PubMed Central

    Kitchen, S; Preston, F E

    1997-01-01

    BACKGROUND: A number of instruments have been developed for determination of prothrombin time (PT) and International Normalised Ratio (INR) at locations not limited to central laboratories. AIM: To evaluate one such portable instrument, the Thrombolytic Assessment System (TAS), which can be used in a near-patient setting. METHODS: Samples from 20 normal subjects and 48 patients treated with warfarin for venous thromboembolic disease were studied. The warfarin group was divided into: initiation phase (n = 10), combined warfarin and heparin (n = 10), stabilised therapy (n = 20), and over anticoagulated patients (n = 8). PTs and INRs were determined in each group using three conventional thromboplastins (Diagen Activated, Manchester Reagent, and Instrumentation Laboratory) and two TAS techniques (whole blood or plasma). An independent International Sensitivity Index (ISI) calibration of the TAS system was performed. RESULTS: Calculated ISIs for the TAS were 1.028 and 0.984 for plasma and whole blood analysis, respectively, compared with manufacturer's values of 0.98 and 0.97. INR results with TAS (whole blood) were 11% less than those obtained with Diagen Activated (p < 0.01) and 16% less than those obtained with Instrumentation Laboratory (p < 0.001) when manufacturers' mean normal PT and ISI were used for TAS INRs. TAS (whole blood) results were similar to TAS plasma or Manchester Reagent results. The use of a locally determined mean normal prothrombin time (MNPT) improved agreement between TAS and the other reagents, abolishing the significant difference between INRs determined with TAS (whole blood) and Diagen Activated techniques. CONCLUSION: The TAS system can be used with whole blood or plasma and produces similar INRs to those obtained with Diagen Activated or Manchester Reagent using manufacturer's ISI and a locally determined MNPT. Results were lower with TAS or Manchester Reagent compared with those obtained with Instrumentation Laboratory thromboplastin

  14. The evolution of anticoagulant therapy

    PubMed Central

    Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe

    2016-01-01

    Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants. PMID:26710352

  15. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring

    PubMed Central

    2013-01-01

    Unlike traditional anticoagulants, the more recently developed agents rivaroxaban, dabigatran and apixaban target specific factors in the coagulation cascade to attenuate thrombosis. Rivaroxaban and apixaban directly inhibit Factor Xa, whereas dabigatran directly inhibits thrombin. All three drugs exhibit predictable pharmacokinetic and pharmacodynamic characteristics that allow for fixed oral doses in a variety of settings. The population pharmacokinetics of rivaroxaban, and also dabigatran, have been evaluated in a series of models using patient data from phase II and III clinical studies. These models point towards a consistent pharmacokinetic and pharmacodynamic profile, even when extreme demographic factors are taken into account, meaning that doses rarely need to be adjusted. The exception is in certain patients with renal impairment, for whom pharmacokinetic modelling provided the rationale for reduced doses as part of some regimens. Although not routinely required, the ability to measure plasma concentrations of these agents could be advantageous in emergency situations, such as overdose. Specific pharmacokinetic and pharmacodynamic characteristics must be taken into account when selecting an appropriate assay for monitoring. The anti-Factor Xa chromogenic assays now available are likely to provide the most appropriate means of determining plasma concentrations of rivaroxaban and apixaban, and specific assays for dabigatran are in development. PMID:23809871

  16. Interactions between Natural Health Products and Oral Anticoagulants: Spontaneous Reports in the Italian Surveillance System of Natural Health Products

    PubMed Central

    Paoletti, Angelica; Gallo, Eugenia; Benemei, Silvia; Vietri, Michele; Lapi, Francesco; Volpi, Roberta; Menniti-Ippolito, Francesca; Gori, Luigi; Mugelli, Alessandro; Firenzuoli, Fabio; Vannacci, Alfredo

    2011-01-01

    Introduction. The safety of vitamin K antagonists (VKA) use can be compromised by many popular herbal supplements taken by individuals. The literature reports that 30% of warfarin-treated patients self-medicates with herbs. Possible interactions represent an health risk. We aimed to identify all herbs-oral anticoagulants interactions collected in the Italian database of suspected adverse reactions to “natural health” products. Methods. The Italian database of spontaneous reports of suspected adverse reactions to natural products was analyzed to address herb-VKAs interactions. Results. From 2002 to 2009, we identified 12 reports with 7 cases of INR reduction in patients treated with warfarin (n = 3) and acenocoumarol (n = 4), and 5 cases of INR increase (all warfarin associated). It was reported 8 different herbal products as possibly interacting. Discussion. Our study confirms the risk of interactions, highlighting the difficulty to characterize them and their mechanisms and, finally, prevent their onset. The reported data underline the urgent need of healthcare providers being aware of the possible interaction between natural products and VKA, also because of the critical clinical conditions affecting patients. This is the first step to have the best approach to understand possible INR alterations linked to herb-VKA interaction and to rightly educate patients in treatment with VKA. PMID:21274401

  17. Safety relevant knowledge of orally anticoagulated patients without self-monitoring: a baseline survey in primary care

    PubMed Central

    2014-01-01

    Background Effective and safe management of oral anticoagulant treatment (OAT) requires a high level of patient knowledge and adherence. The aim of this study was to assess patient knowledge about OAT and factors associated with patient knowledge. Methods This is a baseline survey of a cluster-randomized controlled trial in 22 general practices with an educational intervention for patients or their caregivers. We assessed knowledge about general information on OAT and key facts regarding nutrition, drug-interactions and other safety precautions of 345 patients at baseline. Results Participants rated their knowledge about OAT as excellent to good (56%), moderate (36%) or poor (8%). However, there was a discrepancy between self-rated knowledge and evaluated actual knowledge and we observed serious knowledge gaps. Half of the participants (49%) were unaware of dietary recommendations. The majority (80%) did not know which non-prescription analgesic is the safest and 73% indicated they would not inform pharmacists about OAT. Many participants (35-75%) would not recognize important emergency situations. After adjustment in a multivariate analysis, older age and less than 10 years education remained significantly associated with lower overall score, but not with self-rated knowledge. Conclusions Patients have relevant knowledge gaps, potentially affecting safe and effective OAT. There is a need to assess patient knowledge and for structured education programs. Trial registration Deutsches Register Klinischer Studien (German Clinical Trials Register): DRKS00000586. Universal Trial Number (UTN U1111-1118-3464). PMID:24885192

  18. Coagulation activation after discontinuation of VTE treatment with different oral anticoagulants and impact on 12-month clinical outcomes.

    PubMed

    Beyer-Westendorf, Jan; Gehrisch, Siegmund; Stange, Thoralf; Tittl, Luise; Siegert, Gabriele; Weiss, Norbert

    2015-08-01

    Increasing D-dimer (DD) levels after discontinuation of vitamin K antagonist (VKA) therapy indicate an increased risk of recurrence of venous thromboembolism (VTE). However, after discontinuation of direct-acting non-VKA oral anticoagulants (DOACs or NOACs) the extent of coagulation activation and its clinical impact is unknown. Blood samples were collected from consenting patients with proximal VTE at the end of anticoagulation treatment with apixaban (n=37), dabigatran (n=17), rivaroxaban (n=9) or VKA (n=184) and 4weeks later. DD, prothrombin fragments F1+2 (F1+2) and thrombin-antithrombin complexes (TAT) were measured. All patients underwent follow-up at 12months to establish recurrent VTE or death from any cause. Irrespective of the treatment, DD and F1+2 but not TAT demonstrated a similar increase between baseline and week 4. At 12months, 18 patients (7.3%) had recurrent VTE and two (0.8%) had died. For all patients and subgroups of VKA and DOAC, positive likelihood ratios were numerically higher for baseline values but only TAT values at 4weeks were found to be related to a small increase of outcome event likelihood (2.6; 95%CI 1.23-5.50), which was driven by VKA patients (3.1; 95%CI 1.32-7.30) and not by DOAC patients (2.27; 95%CI 0.52-9.95). For all parameters, negative likelihood ratios were not predictive. In logistic regression analysis, only ΔTAT (optimal cut-off >178% from baseline demonstrated a significant risk increase for VTE/death (odds ratio 3.76; 95% confidence interval 1.46-9.68; p=0.006). In conclusion, the concept of testing coagulation activation parameters may also be transferred to VTE patients at the end of DOAC therapy. For patients with an increase of TAT levels within 4weeks after treatment discontinuation (>178% from baseline) is associated with an increased risk for VTE recurrence or death at 12months.

  19. Addressing Barriers to Optimal Oral Anticoagulation Use and Persistence Among Patients with Atrial Fibrillation: Proceedings, Washington, DC, December 3–4, 2012

    PubMed Central

    Hess, Paul L.; Mirro, Michael J.; Diener, Hans-Christoph; Eikelboom, John W.; Al-Khatib, Sana M.; Hylek, Elaine M.; Bosworth, Hayden B.; Gersh, Bernard J.; Singer, Daniel E.; Flaker, Greg; Mega, Jessica L.; Peterson, Eric D.; Rumsfeld, John S.; Steinberg, Benjamin A.; Kakkar, Ajay K.; Califf, Robert M.; Granger, Christopher B.

    2014-01-01

    Approximately half of patients with atrial fibrillation (AF) and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3–4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to develop and disseminate shared decision-making tools, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational datasets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. PMID:25173533

  20. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care

    PubMed Central

    Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D

    2015-01-01

    Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443

  1. Drug persistence with rivaroxaban therapy in atrial fibrillation patients—results from the Dresden non-interventional oral anticoagulation registry

    PubMed Central

    Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert

    2015-01-01

    Aims Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan–Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8–15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09–1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06–1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). Conclusion Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter. PMID:25694537

  2. Clinical and radiological determinants of prestroke cognitive decline in a stroke cohort

    PubMed Central

    Pohjasvaara, T; Mantyla, R; Aronen, H; Leskela, M; Salonen, O; Kaste, M; Erkinjuntti, T

    1999-01-01

    OBJECTIVES—Stroke seems to be related to dementia more often than previously assumed and vascular factors are also related to Alzheimer's disease. The pathophysiology of poststroke dementia includes ischaemic changes in the brain, a combination of degenerative and vascular changes, and changes only related to Alzheimer's disease. Some cognitive decline recognised after a stroke may be due to pre-existing cognitive decline. The aim of this study was to determine the clinical and radiological determinants of prestroke cognitive decline.
METHODS—The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischaemic stroke completed a comprehensive neuropsychological test battery; structured medical, neurological, and mental status examination; interview of a knowledgeable informant containing structured questions on abnormality in the cognitive functions; assessment of social functions before the index stroke; and MRI.
RESULTS—Frequency of prestroke cognitive decline including that of dementia was 9.2% (31/337). The patients with prestroke cognitive decline were older, more often had less than 6 years of education, and had history of previous stroke. Vascular risk factors did not differ significantly between these two groups. White matter changes (p=0.004), cortical entorhinal, hippocampal, and medial temporal atrophy (p<0.001), cortical frontal atrophy (p=0.008); and any central atrophy (p<0.01), but not the frequencies or volumes of old, silent, or all infarcts on MRI differentiated those with and without prestroke cognitive decline. The correlates of prestroke cognitive decline in logistic regression analysis were medial temporal cortical atrophy (odds ratio (OR) 7.5, 95% confidence interval (95%CI) 3.2-18.2), history of previous ischaemic stroke (OR 4.4, 95% CI 1.8-10.6), and education (OR 0.9, 95% CI 0.8-0.9).
CONCLUSIONS—History of previous stroke, but not volumes or frequencies was found to correlate with

  3. Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy

    PubMed Central

    2009-01-01

    Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a

  4. Anticoagulation-related nephropathy.

    PubMed

    Wheeler, D S; Giugliano, R P; Rangaswami, J

    2016-03-01

    Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.

  5. [Treatment of very old patients with non valvular atrial fibrillation. The valuable opportunity offered by new oral anticoagulants, to be cautiously used].

    PubMed

    Orso, Francesco; Barucci, Riccardo; Fracchia, Stefania; Mannarino, Giulio; Pratesi, Alessandra; Fattirolli, Francesco

    2013-12-01

    Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its incidence increases with age reaching a 10% prevalence in the oldest old. Patients with AF have a five-fold increase in the risk of stroke. Current guidelines on AF management recommend the prescription of oral anticoagulant therapy in patients at medium and high risk of thromboembolic events. Advanced age is a risk factor for stroke in AF, but despite clear evidences a high rate of OAT under prescription is reported and particularly in the oldest old. Among the main causes of this phenomenon an enhanced risk of bleeding is often reported: this due to several factors: risk of falls, the presence of comorbidity and polifarmacy and a reduction in compliance and adherence that are common in the elderly. In recent years the international scenario in the management of OAT has significantly changed since the introduction of the new oral anticoagulants (NOA): Dabigatran, a direct thrombin inhibitor, and two oral factor Xa inhibitors Rivaroxaban and Apixaban, which have all been tested in randomized clinical trial (RELY, ROCKET-AF e ARISTOTLE) which have demonstrated non inferiority compared to warfarin in the prevention of thromboembolic events with an optimal safety profile. NOA could be an important therapeutic opportunity for stroke prevention in elderly patients with AF even if the substantial differences in mean age, anthropometric measures and comorbidity of the patients enrolled in these trials compared with those of the real world setting, oblige some caution and discussion.

  6. 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

  7. Point of care monitoring of oral anticoagulant therapy in children: comparison of CoaguChek Plus and Thrombotest methods with venous international normalised ratio.

    PubMed

    Ignjatovic, Vera; Barnes, Chris; Newall, Fiona; Hamilton, Simone; Burgess, Janet; Monagle, Paul

    2004-10-01

    This paper reports the outcome of a research protocol aimed at optimising warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the standard monitoring test employed to manage oral anticoagulant therapy in children at the Royal Children's Hospital (RCH), Melbourne. This study compares the results of this standard method to the novel CoaguChek INR monitor and the "gold standard" technique of venous INR sampling. The objectives were to determine 1) if point-of-care techniques of measuring the INR (Thrombotest and CoaguChek) are accurate and reliable compared to INR results obtained from venous sampling, processed in an accredited laboratory, and 2) if INR results generated by POC devices can be safely used to manage oral anticoagulant therapy in children. 18 children (10 females and 8 males) participated in the study. Ages ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR, values obtained with Coaguchek and Thrombotest crossed into or out of the therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek cases and 57% Thrombotest cases, the difference from the venous result was less than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable method compared to Thrombotest, in the pediatric population tested, and can be safely used to manage oral anticoagulant therapy in children.

  8. Anticoagulation: monitoring of patients receiving anticoagulation.

    PubMed

    Hawes, Emily M; Viera, Anthony J

    2014-07-01

    For patients with acute venous thromboembolism treated with warfarin, parenteral anticoagulation should be continued for a minimum of 5 days and until the international normalized ratio (INR) is 2 or greater for at least 24 hours. Early initiation of warfarin therapy is recommended. The goal therapeutic INR range for patients treated with warfarin is most commonly 2 to 3. During maintenance warfarin therapy, validated decision-support tools should be used to guide dosing. For patients with stable INRs, frequency of INR testing can be extended from every 4 weeks to up to 12 weeks. Self-testing and self-management can be safe options for patients receiving warfarin who are motivated and show competence. Patients starting anticoagulation therapy should receive education on treatment goals, adverse effects, and monitoring strategy. Physicians deciding whether to prescribe one of the new oral anticoagulants instead of warfarin should assess for possible drug interactions and for renal and hepatic impairment and should consider the financial cost to the patient. No routine coagulation assay monitoring is required for patients receiving apixaban, dabigatran, or rivaroxaban. Physicians who oversee oral anticoagulation therapy should do so in a systematic and coordinated fashion.

  9. Quantitation of the Oral Anticoagulants Dabigatran, Rivaroxaban, Apixaban, and Warfarin in Plasma Using Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS).

    PubMed

    Noguez, Jaime H; Ritchie, James C

    2016-01-01

    This chapter describes a method to measure the oral anticoagulants dabigatran, rivaroxaban, apixaban, and warfarin in plasma samples using ultra-performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS). The instrument is operated in multiple reaction monitoring (MRM) mode with an electrospray ionization (ESI) source in positive ionization mode. Samples are extracted with a 90:10 methanol/0.1 N hydrochloric acid solution containing stable isotope-labeled internal standards for each analyte. After centrifugation the supernatant is transferred to a mass spectrometry vial, injected onto the UPLC-ESI-MS/MS, and quantified using an eight-point calibration curve.

  10. Twice- or Once-Daily Dosing of Novel Oral Anticoagulants for Stroke Prevention: A Fixed-Effects Meta-Analysis with Predefined Heterogeneity Quality Criteria

    PubMed Central

    Clemens, Andreas; Noack, Herbert; Brueckmann, Martina; Lip, Gregory Y. H.

    2014-01-01

    Background A number of novel oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) are in clinical use for various indications. The dosing regimens differ between twice-daily and once-daily dosing for the prevention of stroke in patients with atrial fibrillation. With the availability of the results from four phase 3 studies (>70,000 patients), we explored whether twice-daily or once-daily dosing provides better risk-benefit balance among novel oral anticoagulants. Methods We conducted a strict, stepwise, fixed-effects meta-analysis with predefined heterogeneity quality criteria to generate the most appropriate common estimates for twice-daily (BID) or once-daily (QD) dosing regimens. An indirect comparison of these dosing regimens with fixed-effects meta-analysis common estimates (where available), or individual compound results, was done respectively. Results Comparing indirectly BID vs QD dosing regimens resulted in hazard ratios (HR [95% confidence interval]) for stroke and systemic embolism of 0.75 (0.58–0.96) for dabigatran 150 mg BID, and 0.91 (0.73–1.13) for apixaban BID vs the QD dosing regimen. For ischemic stroke, the HR of BID vs QD was 0.85 (0.69–1.05). For intracranial hemorrhage, BID vs rivaroxaban QD was 0.57 (0.37–0.88) and, vs edoxaban QD, 0.81 (0.54–1.22). Due to heterogeneity, common estimates for major bleeding QD or BID were not justified, therefore indirect comparison of regimens were not possible. All non-vitamin K antagonist oral anticoagulants reduced all-cause mortality vs warfarin with a HR of 0.90 (0.86–0.96) without differences between regimen. Conclusions Based on the available phase 3 study evidence, the twice-daily dosing regimen of non-vitamin K antagonist oral anticoagulants appears to offer a more balanced risk-benefit profile with respect to stroke prevention and intracranial hemorrhage. PMID:24911432

  11. Pre-stroke living situation and depression contribute to initial stroke severity and stroke recovery

    PubMed Central

    Aron, Abraham W.; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D.

    2014-01-01

    Substantial evidence from both experimental and clinical studies has demonstrated that social isolation can increase stroke incidence and impair recovery. Social isolation leads to higher rates of recurrent stroke but is often not reported as a risk factor. We examined prospectively collected stroke center database variables, which included pre-stroke living situation, to determine if social isolation could be determined from existing data using living arrangement as a proxy. Patients were categorized into 4 groups hypothesized to represent increasing levels of social isolation: Living with Spouse, Living with Family, Living alone with visiting services and Living Alone. Initial stroke severity and recovery were measured using the National Institutes of Health Stroke Scale and Barthel Index, respectively. A multivariate model was used to determine the relationship between pre-stroke living situation, stroke severity and functional outcome. Patients living alone had less severe strokes on admission and better recovery at 3 months compared to the other cohorts. Patients living alone or those that lived with a spouse had less severe strokes on presentation and better recovery at both 3 and 12 months after stroke compared to the other cohorts. However, upon detailed examination, it was found that these patients also had significantly higher pre-stroke function. Pre-existing depression was significantly higher in women and depressed patients had poorer outcomes 3 months after stroke. Information regarding isolation is notably absent from most large stroke databases. A more comprehensive evaluation of social interaction should be obtained to more accurately measure social isolation. PMID:25524014

  12. Prestroke living situation and depression contribute to initial stroke severity and stroke recovery.

    PubMed

    Aron, Abraham W; Staff, Ilene; Fortunato, Gilbert; McCullough, Louise D

    2015-02-01

    Substantial evidence from both experimental and clinical studies has demonstrated that social isolation can increase stroke incidence and impair recovery. Social isolation leads to higher rates of recurrent stroke but is often not reported as a risk factor. We examined prospectively collected stroke center database variables, which included prestroke living situation, to determine if social isolation could be determined from existing data using living arrangement as a proxy. Patients were categorized into 4 groups hypothesized to represent increasing levels of social isolation: living with spouse, living with family, living alone with visiting services, and living alone. Initial stroke severity and recovery were measured using the National Institutes of Health Stroke Scale and Barthel Index, respectively. A multivariate model was used to determine the relationship among prestroke living situation, stroke severity, and functional outcome. Patients living alone had less severe strokes on admission and better recovery at 3 months compared with the other cohorts. Patients living alone or those who lived with a spouse had less severe strokes on presentation and better recovery at both 3 and 12 months after stroke compared with the other cohorts. However, on detailed examination, it was found that these patients also had significantly higher prestroke function. Pre-existing depression was significantly higher in women, and depressed patients had poorer outcomes 3 months after stroke. Information regarding isolation is notably absent from most large stroke databases. A more comprehensive evaluation of social interaction should be obtained to more accurately measure social isolation.

  13. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S

    2016-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional

  14. Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

    PubMed Central

    Kwon, Chang Hee; Kim, Minsu; Kim, Jun; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asian octogenarian atrial fibrillation (AF) patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged ≥ 80 years with non-valvular AF who had taken either NOACs (148 cases, 50.5%) or warfarin (145 cases, 49.5%) were retrospectively reviewed. The efficacy outcome was the composite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years (172 patient-years with NOACs and 203 patient-years with warfarin). Patients on NOACs were slightly older (P = 0.006) and had slightly higher HAS-BLED scores (P = 0.034). The efficacy of both anticoagulants was high (1.16% for NOACs vs. 2.98% for warfarin per 100 patient-years, P = 0.46). The safety outcome was relatively high in both NOACs and warfarin groups (8.96% vs. 12.46%, P = 0.29). The efficacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin (0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34). Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population. PMID:27605936

  15. Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

    PubMed Central

    Kwon, Chang Hee; Kim, Minsu; Kim, Jun; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asian octogenarian atrial fibrillation (AF) patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged ≥ 80 years with non-valvular AF who had taken either NOACs (148 cases, 50.5%) or warfarin (145 cases, 49.5%) were retrospectively reviewed. The efficacy outcome was the composite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years (172 patient-years with NOACs and 203 patient-years with warfarin). Patients on NOACs were slightly older (P = 0.006) and had slightly higher HAS-BLED scores (P = 0.034). The efficacy of both anticoagulants was high (1.16% for NOACs vs. 2.98% for warfarin per 100 patient-years, P = 0.46). The safety outcome was relatively high in both NOACs and warfarin groups (8.96% vs. 12.46%, P = 0.29). The efficacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin (0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34). Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population.

  16. The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies.

    PubMed

    He, Ying; Wong, Ian C K; Li, Xue; Anand, Shweta; Leung, Wai K; Siu, Chung Wah; Chan, Esther W

    2016-07-01

    Particular concerns have been raised regarding the association between non-vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a systematic review with a meta-analysis to examine the association between NOACs and GIB in real-life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random-effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta-analysis, enrolling 1442 GIB cases among 106 626 dabigatran users (49 486 patient-years), and 184 GIB cases among 10 713 rivaroxaban users (4046 patient-years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient-years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose-related effect of dabigatran, with a significantly higher risk of GIB for 150 mg b.i.d. (RR = 1.51, 95% CI 1.34, 1.70) but not for 75 mg b.i.d. or 110 mg b.i.d.. In addition, the use of proton pump inhibitors (PPIs)/histamine H2-receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta-analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk. PMID:26889922

  17. Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

    PubMed Central

    Skjøth, Flemming; Nielsen, Peter Brønnum; Kjældgaard, Jette Nordstrøm; Lip, Gregory Y H

    2016-01-01

    Objective To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation. Design Observational nationwide cohort study. Setting Three Danish nationwide databases, August 2011 to October 2015. Participants 61 678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35 436, 57%), dabigatran 150 mg (n=12 701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%). Main outcome measures Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding. Results When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5

  18. Anticoagulant Therapy-Induced Gallbladder Hemorrhage after Cardiac Valve Replacement

    PubMed Central

    Cho, Seong Ho; Lee, Hae Young; Kim, Hyun Su

    2015-01-01

    Anticoagulation therapy is essential after cardiac valve surgery. However, spontaneous bleeding remains a major concern during anticoagulation therapy. Spontaneous gallbladder (GB) hemorrhage (hemobilia) is a rare occurrence during standard anticoagulation therapy. This report presents a case of GB hemorrhage that occurred shortly after initiating oral anticoagulant therapy in a patient who had undergone mitral valve replacement surgery. PMID:26665115

  19. Anticoagulation in atrial fibrillation

    PubMed Central

    Piccini, Jonathan P

    2014-01-01

    Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin’s shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535

  20. Implementation of non-vitamin K antagonist oral anticoagulants in daily practice: the need for comprehensive education for professionals and patients.

    PubMed

    Heidbuchel, Hein; Berti, Dana; Campos, Manuel; Desteghe, Lien; Freixo, Ana Parente; Nunes, António Robalo; Roldán, Vanessa; Toschi, Vincenzo; Lassila, Riitta

    2015-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for the prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. NOACs do not require routine coagulation monitoring, creating a challenge to established systems for patient follow-up based on regular blood tests. Healthcare professionals (HCPs) are required to cope with a mixture of patients receiving either a vitamin K antagonist or a NOAC for the same indications, and both professionals and patients require education about the newer drugs. A European working group convened to consider the challenges facing HCPs and healthcare systems in different countries and the educational gaps that hinder optimal patient management. Group members emphasised the need for regular follow-up and noted national, regional and local variations in set-up and resources for follow-up. Practical incorporation of NOACs into healthcare systems must adapt to these differences, and practical follow-up that works in some systems may not be able to be implemented in others. The initial prescriber of a NOAC should preferably be a true anticoagulation specialist, who can provide initial patient education and coordinate the follow-up. The long-term follow-up care of patients can be managed through specialist coagulation nurses, in a dedicated anticoagulation clinic or by general practitioners trained in NOAC use. The initial prescriber should be involved in educating those who perform the follow-up. Specialist nurses require access to tools, potentially including specific software, to guide systematic patient assessment and workflow. Problem cases should be referred for specialist advice, whereas in cases for which minimal specialist attention is required, the general practitioner could take responsibility for patient follow-up. Hospital departments and anticoagulation clinics should proactively engage with all downstream HCPs (including pharmacists) to ensure

  1. Phase III trials of new oral anticoagulants in the acute treatment and secondary prevention of VTE: comparison and critique of study methodology and results.

    PubMed

    Cohen, Alexander T; Imfeld, Stephan; Rider, Thomas

    2014-05-01

    The traditional treatment of venous thromboembolism (VTE) has been use of heparin and vitamin K antagonists (VKA), and although shown to be effective, they have numerous limitations. New oral anticoagulants (NOACs) including direct thrombin (factor IIa) inhibitors (dabigatran) and selective factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) have emerged as promising alternatives with the potential to overcome the limitations of traditional treatments. Clinical trials have been performed with a view to making significant changes to the acute, long-term and extended treatment of VTE. Data are now available on the efficacy and safety, including bleeding rates, of the NOACs in comparison with VKA in the acute treatment and secondary prevention of VTE as well as in comparison with placebo extended VTE treatment. This review compares and contrasts the design and results of the Phase III trials of NOACs in VTE and discusses the implications of the NOACs in terms of treatment strategies in VTE patients.

  2. Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a systematic and qualitative review.

    PubMed

    Liberato, Nicola Lucio; Marchetti, Monia

    2016-01-01

    The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) into clinical practice represented a major change in the treatment of non-valvular atrial fibrillation (NVAF); drugs as effective as the gold standard were available, rapidly functioning and without major interferences with drugs and foods. However, a huge increase in the economic burden of NVAF was predicted, and many cost-effectiveness analyses were developed to aid policy makers and clinicians in implementing strategies for the prevention of stroke in NVAF. The present systematic review identified 54 studies from 21 different countries, reporting the incremental cost-effectiveness of dabigatran, apixaban, rivaroxaban and edoxaban. A critical appraisal of the studies was conducted in order to highlight consolidated results and biases. PMID:26817497

  3. New-onset atrial fibrillation after recent coronary stenting: Warfarin or non-vitamin K-antagonist oral anticoagulants to be added to aspirin and clopidogrel? A viewpoint.

    PubMed

    Rubboli, Andrea; Agewall, Stefan; Huber, Kurt; Lip, Gregory Y H

    2015-10-01

    The antithrombotic management of patients on oral anticoagulation (OAC), with either warfarin or non-vitamin K-antagonist oral anticoagulants (NOACs), undergoing percutaneous coronary intervention with stent (PCI-S) has been recently addressed in a joint European consensus document. In accordance, triple therapy (TT) of OAC, aspirin and clopidogrel should generally be given as the initial therapy. More uncertainty exists over whether warfarin or a NOAC should be added in patients already on dual antiplatelet therapy of aspirin and clopidogrel (DAPT) after recent PCI-S. Upon review of available data, it appears that the risk of major bleeding of TT as compared to DAPT is similar with either warfarin or a NOAC. In particular, TT consistently appears associated to an approximately 2.5 fold increase in the risk of major bleeding. Because of the higher convenience, NOACs might be considered the preferred OAC to be added to DAPT. Given the reported different safety profiles of the various NOACs on the incidence of major, and gastrointestinal, bleeding, the NOACs, and the dose, showing the greatest safety in this regard should be selected. In accordance, dabigatran 110 mg and apixaban 2.5mg twice daily appear as the most valuable options in patients who are not and who are respectively, at increased risk of bleeding. As an alternative, apixaban 5mg twice daily might be considered in patients at risk of bleeding not increased, whereas rivaroxaban 15 mg once daily may be considered in the presence of increased risk of bleeding (essentially when related to moderate renal impairment). PMID:26093527

  4. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

    Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Halperin, Jonathan L.; Breithardt, Günter; Passman, Rod; Hankey, Graeme J.; Patel, Manesh R.; Becker, Richard C.; Singer, Daniel E.; Hacke, Werner; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A.A.; Califf, Robert M.; Piccini, Jonathan P.

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  5. Macroscopic hematuria in patients on anticoagulation therapy

    PubMed Central

    Mariyanovski, Valeri; Hadzhiyska, Valeria

    2015-01-01

    Introduction Visible hematuria is not rare in patients on anticoagulant therapy. There is no consensus regarding the diagnostic approach for them; some authors suggest restricted volume of diagnostic procedures because of the low number of urological etiology found. Some antibiotics have been reported to potentiate the effect of oral anticoagulants. Material and methods The study addresses the need for urological assessment of patients on anticoagulation therapy and the possible role of some drugs administrated simultaneously with an oral anticoagulant, for the onset of macroscopic hematuria. Patients hospitalized with hematuria, both with or without anticoagulation therapy, were investigated and followed up. Results The onset of hematuria depends on the monitoring of oral anticoagulation. INR (International Normalized Ratio) value corresponds with the probability of non-urological etiology, where INR>4 carries relatively low risk for urological and malignant etiology. Some antibiotics may influence the anticoagulation effect, so INR value may be elevated and hematuria may occur. Conclusions Anticoagulation therapy should be administrated carefully and individually. The risk of urological etiology of hematuria is lower in patients on oral anticoagulants (especially when INR >4), however, it is not zero. PMID:26568876

  6. Anticoagulant rodenticides.

    PubMed

    Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister

    2005-01-01

    Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to

  7. 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

  8. Anticoagulation therapy.

    PubMed

    Ginsberg, J A; Crowther, M A; White, R H; Ortel, T L

    2001-01-01

    Despite refinements and standardization in the use of anticoagulants, many problems remain for clinicians. Dr. Crowther describes appropriate starting and maintenance doses of warfarin, factors accounting for inter- and intra-observer variability and importantly, the management of the over-anticoagulated patients and bleeding patients. Dr. White compares unfractionated heparin (UFH) and low molecular weight heparin (LMWH) and addresses whether there truly are differences in the efficacy and safety of different LMWH's for both arterial and venous indications. Dr. Ortel discusses the management of the problem patient who requires anticoagulants, the management of heparin-induced thrombocytopenia, the pregnant patient, the obese patient, patients who have renal insufficiency and/or liver disease, patients with malignant disease, and other challenging patient populations.

  9. Validation of the international normalized ratio (INR) in a new point-of-care system designed for home monitoring of oral anticoagulation therapy.

    PubMed

    Plesch, W; van den Besselaar, A M H P

    2009-02-01

    The new CoaguChek XS system is designed for use in patient self testing with a measuring range from 0.8 INR up to 8.0 INR, which has been calibrated against the mean INR of rTF/95 and ERM-AD149. This study was performed to confirm the correct INR results received from two routinely manufactured lots of test strips when compared with the international reference preparations (IRP) rTF/95 and ERM-AD149. At one study site capillary and noncitrated venous whole blood samples from 20 normal donors and 62 anticoagulated patients were applied to two test strip lots of the new system in duplicate. Additionally blood was collected in citrate tubes, processed to plasma, and PT results were obtained using rTF/95 and ERM-AD149 by the manual tilt tube method. Method comparisons of the INR results of the CoaguChek XS system vs. the mean INR of the IRP demonstrated a mean relative bias of -0.02% to -0.4%, mean absolute relative deviations of 6.4-9.6%, and accuracy observing >95% of CoaguChek XS INR within limits of +/-14% to +/-21.5% to the mean INR of the IRP. The results of the study confirm the successful calibration of two lots of the new CoaguChek XS system, demonstrate the validity of the calibration concept and prove the accuracy of the new system in comparison with the IRP. Clinical decisions in oral anticoagulation therapy may be reliably made upon the INR results of the new system.

  10. Therapeutic concordance of two portable monitors and two routine automatic oral anticoagulant monitoring systems using as reference the manual prothrombin time technique.

    PubMed

    Vacas, Marta; Lafuente, Pedro José; Unanue, Iciar; Santos, Mónica; Iriarte, Jose Antonio

    2003-01-01

    Two models of capillary blood prothrombin time (PT) monitoring systems were evaluated for analytical performance and then compared with two routine PT systems using the reference manual technique and a high-sensitivity thromboplastin. Two sets of 60 and 80 plasmas were analyzed from anticoagulated patients stabilized over 3 months in an INR range 2-3.5 for therapy. Capillary PT determination was performed in two portable monitors, CoaguChek S and CoaguChek PT (Roche Diagnostics), and plasma automatic methods were Neoplastine/STA (Diagnostics Stago) and PT-FibrinogenHsPlus/ACL7000 (Instrumental Laboratories). Thromboplastin Bilbao (TBi), an in-house high-sensitivity rabbit thromboplastin (ISI=1.08), recommended as the reference reagent by an External Spanish Oral Anticoagulant Quality Assessment, was used in the PT manual technique. The two monitors' coefficients of correlation with the reference system were 0.74 for CoaguChek S and 0.81 for CoaguChek PT. The automatic routine systems showed a correlation of 0.92 (Neoplastine/STA) and 0.91 (PT-FbHsPlus/ACL7000). Clinical agreement expressed as the percentage of simple correlation ranged between 75.0% (CoaguChek S) and 88.9% (Neoplastine/STA). The systems having the best kappa index with the manual technique were CoaguChek PT (71.9%) and the Neoplastine/STA system (73%). The routine PT management systems exhibited better correlation and percentage of concordance when using the TBi/manual technique than did the portable monitors, which moreover performed unequally in this regard.

  11. Results from the Registry of Atrial Fibrillation (AFABE): Gap between Undiagnosed and Registered Atrial Fibrillation in Adults—Ineffectiveness of Oral Anticoagulation Treatment with VKA

    PubMed Central

    Panisello-Tafalla, Anna; Clua-Espuny, Josep Lluís; Gil-Guillen, Vicente F.; González-Henares, Antonia; Queralt-Tomas, María Lluisa; López-Pablo, Carlos; Lucas-Noll, Jorgina; Lechuga-Duran, Iñigo; Ripolles-Vicente, Rosa; Carot-Domenech, Jesús; López, Miquel Gallofré

    2015-01-01

    Objective. This study aimed to examine the effectiveness of the use of oral anticoagulation (OAC) medication, recommended by national guidelines for stroke prevention but reportedly underused in AF patients with moderate to high stroke risk. Method. A multicentre and cross-sectional study of undiagnosed AF among out-of-hospital patients over 60 years old was carried out, visiting 3,638 patients at primary health centres or at home for AF diagnosis using the IDC-10 classification. The main outcome measures were CHA2DS2VASC, HAS-BLED scores, cardiovascular comorbidity, pharmacological information, TTR, and SAMe-TT2R2 scores. Results. The main findings were undiagnosed AF in 26.44% of cases; 31.04% registered with AF but not using OAC despite 95.6% having a CHA2DS2VASC ≥ 2 score; a risk of bleeding in important subgroups using OAC without indication (37.50% CHA2DS2VASC < 2 score); the use of OAC with TTR < 60% (33.1%), of whom 47.6% had a HAS-BLED score ≥3. Thus, 35.4% of the expected AF prevalence achieved an optimal time in the therapeutic range. Conclusions. The expected AF prevalence was 10.9% (n 5267), but the registered prevalence was 7.5% (n 3638). Only 35.04% (CI = 95%, 33.7–36.3) of AF patients treated with vitamin K antagonists (VKAs) achieve the goal of TTR > 60%. PMID:26229954

  12. Widening the path and window of opportunity for FDA approval of non-vitamin K oral anticoagulant specific antidotes and reversal agents.

    PubMed

    Patel, Sunny; Steen, Dylan

    2016-02-01

    There remains a need for safe, immediately effective, and easy to administer antidotes for patients taking novel oral anticoagulants (NOACs) in the settings of major bleeding, need for emergency surgery, and accidental overdose. We review considerations for the successful safety and effectiveness evaluation of potential antidotes currently under development. These compounds are in expedited regulatory approval programs aimed at accelerating the preclinical and clinical evaluation and approval processes for treatments of serious conditions. We review the features of these expedited programs as well as the FDA's efforts to broadly advance the efficiency of drug development and increase the number of new compounds brought to market. The critical path initiative and regulatory science initiative have resulted in numerous successful programs to address current challenges such as a paucity of validated biomarkers and surrogate endpoints as well as unreliable animal models of toxicity. The FDA has also advocated for increased use of pharmacokinetic/pharmacodynamic modeling and adaptive trial design. These efforts foster collaboration between academia, industry and the public sector across interdisciplinary sciences and may continue to widen the pathway for NOAC-specific reversal agents and other novel compounds.

  13. Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis

    PubMed Central

    Cohen, A. T.; Hamilton, M.; Bird, A.; Mitchell, S. A.; Li, S.; Horblyuk, R.; Batson, S.

    2016-01-01

    Background Historically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months) of VTE. Data from Phase III randomised controlled trials (RCTs) are now available for non-VKA oral anticoagulants (NOACs) in this indication. The current systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE. Methods Electronic databases (accessed July 2014 and updated April 2016) were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs). Sensitivity analyses examining (i) the dataset employed according to the time frame for outcome assessment (ii) the model used for the NMA were conducted. Results Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the composite efficacy outcome (VTE and VTE-related death) was statistically significantly lower with the NOACs and warfarin INR 2.0–3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a statistically significantly reduced risk of ‘major or clinically relevant non-major bleed’ compared with warfarin INR 2.0–3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed. Conclusions Results from the NMA indicate that NOACs are an effective treatment for prevention of

  14. Contraindications to Anticoagulation Therapy and Eligibility for Novel Anticoagulants in Older Patients With Atrial Fibrillation

    PubMed Central

    Steinberg, Benjamin A.; Greiner, Melissa A.; Hammill, Bradley G.; Curtis, Lesley H.; Benjamin, Emelia J.; Heckbert, Susan R.; Piccini, Jonathan P.

    2015-01-01

    Aims Oral anticoagulation therapy prevents stroke and improves survival in patients with atrial fibrillation, but the therapy is underutilized. We sought to identify the prevalence of contraindications for oral anticoagulation and the proportion of patients potentially eligible for different agents. Methods We identified patients with nonacute atrial fibrillation in a nationally representative 5% sample of 2009 Medicare data. We divided the population into patients ineligible for any oral anticoagulant, patients eligible for warfarin only, and patients eligible for any anticoagulant. We compared patient characteristics and the use of anticoagulation among the subgroups. Results Among 86,671 patients with atrial fibrillation, 1872 (2.2%) were ineligible for anticoagulation because of an absolute contraindication, most frequently a history of intracranial hemorrhage (60%). Patients ineligible for any anticoagulant were the same age as the overall group (mean age, 80.5 vs 80.4 years). However, they had higher rates of dementia (19% vs 8.6%) and heart failure (59% vs 43%) and higher mean CHADS2 scores (3.8 vs 2.8). Of the remaining 84,799 patients eligible for anticoagulation, 7146 (8.4%) had were eligible for warfarin only (most commonly because of mechanical heart valves [66%] and end-stage renal disease [12%]). Sixty-five percent of patients eligible for anticoagulation received warfarin, and the proportion was similar for patients with a relatively high risk of bleeding. Conclusions Older adults with atrial fibrillation rarely have absolute contraindications to oral anticoagulation therapy. Among patients without contraindications, most appeared to be eligible for any anticoagulant, and relatively high-risk features appeared not to influence warfarin use. PMID:25930214

  15. Values and preferences in oral anticoagulation in patients with atrial fibrillation, physicians' and patients' perspectives: protocol for a two-phase study

    PubMed Central

    Alonso-Coello, Pablo; Montori, Victor M; Solà, Ivan; Schünemann, Holger J; Devereaux, Philip J; Charles, Cathy; Roura, Mercè; Díaz, M Gloria; Souto, Juan Carlos; Alonso, Rafael; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Diez, Ana Isabel; Gich, Ignasi; Guyatt, Gordon

    2008-01-01

    Background Oral anticoagulation prevents strokes in patients with atrial fibrillation but, for reasons that remain unclear, less than 40% of all patients with atrial fibrillation receive warfarin. The literature postulates that patient and clinician preferences may explain this low utilization. Design The proposed research seeks to answer the following questions: i) When assessed systematically, do patients' and clinicians' preferences explain the utilization of warfarin to prevent strokes associated with atrial fibrillation? ii) To what extent do patients' and clinicians' treatment preferences differ? iii) What factors explain any differences that exist in treatment preferences between patients and clinicians? To answer these questions we will conduct a two-phase study of patient and clinician preferences for health states and treatments. In the first phase of this study we will conduct structured interviews to determine their treatment preferences for warfarin vs. aspirin to prevent strokes associated with atrial fibrillation using the probability trade-off technique. In the same interview, we will conduct preference-elicitation exercises using the feeling thermometer to identify the utilities that patients place on taking medication (warfarin and aspirin), and on having a mild stroke, a severe stroke, and a major bleed. In the second phase of the study we will convene focus groups of clinicians and patients to explore their answers to the exercises in the first phase. Discussion This is a study of patient and clinician preferences for health states and treatments. Because of its clinical importance and our previous work in this area, we will conduct our study in the clinical context of the decision to use antithrombotic agents to reduce the risk of stroke in patients with non-valvular chronic atrial fibrillation PMID:18954427

  16. Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation: Temporal trends 2011-2015 in Denmark.

    PubMed

    Staerk, Laila; Fosbøl, Emil Loldrup; Gadsbøll, Kasper; Sindet-Pedersen, Caroline; Pallisgaard, Jannik Langtved; Lamberts, Morten; Lip, Gregory Y H; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar; Olesen, Jonas Bjerring

    2016-01-01

    Among atrial fibrillation (AF) patients, Danish nationwide registries (2011-2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban (13%), or apixaban (16%) were included with mean age (SD) 72.1 (11.3), 71.5 (11.0), 74.3 (11.1), and 75.3 (11.1) years, respectively. Patients aged ≥85 years comprised 15%. Trend tests showed increase in patients ≥85 years initiating OAC (p < 0.0001). VKA usage decreased from 92% to 24% (p < 0.0001). This decrease was independent of age. Dabigatran was the most common non-VKA OAC (NOAC) (40% users), but usage decreased from 2014 until study end (6%) (p < 0.0001). Apixaban was the most used OAC at study end (41%), in particular among those ≥85 years (44%). Compared with patients aged <65 years, the odds ratios associated with initiating VKA, dabigatran, rivaroxaban, or apixaban for patients aged ≥85 years were 0.81 (95% CI 0.75-0.86), 0.65 (95% CI 0.60-0.70), 1.52 (95% CI 1.38-1.67), and 2.09 (95% CI 1.89-2.30), respectively. In conclusion, substantial increase in NOAC usage has occurred. Increasing age was associated with upstart of rivaroxaban or apixaban with reference to age <65 within the specific agent. PMID:27510920

  17. Acute physical exercise is safe in patients with primary antiphospholipid syndrome with exclusive venous thrombosis and under oral anticoagulation with warfarin.

    PubMed

    Garcia, Carolina Borges; Seguro, Luciana Parente Costa; Perandini, Luiz Augusto; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Negrão, Carlos Eduardo; Bonfa, Eloisa; Borba, Eduardo Ferreira

    2014-12-01

    The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

  18. Prothrombin time on admission in patients with cardioembolic stroke and intracranial hemorrhage occurring during warfarin treatment in the direct oral anticoagulant era.

    PubMed

    Okumura, Ken; Hagii, Joji; Metoki, Norifumi; Saito, Shin; Shiroto, Hiroshi; Yasujima, Minoru; Tomita, Hirofumi

    2016-05-31

    Warfarin is used worldwide to prevent cardioembolic stroke (CES) in patients with atrial fibrillation even in the era of direct oral anticoagulant (DOAC). We evaluated clinical characteristics of the patients with CES and intracerebral hemorrhage (ICH) occurring during warfarin treatment, focusing on prothrombin time-international normalized ratio (PT-INR) at the occurrence. The consecutive 846 CES patients (78 ± 9 years) and 870 ICH patients (68 ± 13 years) admitted to the Hirosaki Stroke and Rehabilitation Center from April 2011 through March 2015 were studied. The antithrombotic agents administered in CES patients before the onset included antiplatelets in 146 patients (17%), warfarin in 205 (24%), DOAC in 37 (5%), and none in the other 458 (54%). Mean PT-INR within 24 hours after the onset in nonvalvular atrial fibrillation patients with warfarin was 1.34 ± 0.33 (n = 129), and 111 of them (86%) showed PT-INR value below the recommended therapeutic range in Japan. The antithrombotic agents administered in ICH patient included antiplatelets in 87 patients (10%), warfarin in 86 (10%), DOAC in 8 (1%), and none in the other 689 (79%). Mean PT-INR within 24 hours after the onset in patients with warfarin was 2.27 ± 0.62 (n = 65), and 56 of them (86%) showed PT-INR < 2.8. Thus, there is a large population with poor warfarin control complicating CES and that with good warfarin control complicating ICH, indicating limitation of warfarin treatment in the DOAC era. PMID:27151227

  19. Comparison of treatment effect estimates of non-vitamin K antagonist oral anticoagulants versus warfarin between observational studies using propensity score methods and randomized controlled trials.

    PubMed

    Li, Guowei; Holbrook, Anne; Jin, Yanling; Zhang, Yonghong; Levine, Mitchell A H; Mbuagbaw, Lawrence; Witt, Daniel M; Crowther, Mark; Connolly, Stuart; Chai-Adisaksopha, Chatree; Wan, Zhongxiao; Cheng, Ji; Thabane, Lehana

    2016-06-01

    Emerging observational studies using propensity score (PS) methods assessed real-world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98-1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87-1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83-0.94 for the PS studies; HR 0.79, 95 % CI 0.72-0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79-1.05 for the PS studies; HR 0.85, 95 % CI 0.73-1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non-valvular AF from PS studies are found to be in agreement with those from RCTs. PMID:27370013

  20. Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation: Temporal trends 2011–2015 in Denmark

    PubMed Central

    Staerk, Laila; Fosbøl, Emil Loldrup; Gadsbøll, Kasper; Sindet-Pedersen, Caroline; Pallisgaard, Jannik Langtved; Lamberts, Morten; Lip, Gregory Y. H.; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar; Olesen, Jonas Bjerring

    2016-01-01

    Among atrial fibrillation (AF) patients, Danish nationwide registries (2011–2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban (13%), or apixaban (16%) were included with mean age (SD) 72.1 (11.3), 71.5 (11.0), 74.3 (11.1), and 75.3 (11.1) years, respectively. Patients aged ≥85 years comprised 15%. Trend tests showed increase in patients ≥85 years initiating OAC (p < 0.0001). VKA usage decreased from 92% to 24% (p < 0.0001). This decrease was independent of age. Dabigatran was the most common non-VKA OAC (NOAC) (40% users), but usage decreased from 2014 until study end (6%) (p < 0.0001). Apixaban was the most used OAC at study end (41%), in particular among those ≥85 years (44%). Compared with patients aged <65 years, the odds ratios associated with initiating VKA, dabigatran, rivaroxaban, or apixaban for patients aged ≥85 years were 0.81 (95% CI 0.75–0.86), 0.65 (95% CI 0.60–0.70), 1.52 (95% CI 1.38–1.67), and 2.09 (95% CI 1.89–2.30), respectively. In conclusion, substantial increase in NOAC usage has occurred. Increasing age was associated with upstart of rivaroxaban or apixaban with reference to age <65 within the specific agent. PMID:27510920

  1. Considerations for Systemic Anticoagulation in ESRD.

    PubMed

    Dager, William E; Tsu, Laura V; Pon, Tiffany K

    2015-01-01

    In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.

  2. Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

    PubMed

    Saji, Naoki; Kimura, Kazumi; Tateishi, Yohei; Fujimoto, Shigeru; Kaneko, Nobuyuki; Urabe, Takao; Tsujino, Akira; Iguchi, Yasuyuki

    2016-11-01

    The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

  3. 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

  4. Engaging with quality improvement in anticoagulation management.

    PubMed

    Barnes, Geoffrey D; Kline-Rogers, Eva

    2015-04-01

    Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process.

  5. Engaging with quality improvement in anticoagulation management

    PubMed Central

    Barnes, Geoffrey D.; Kline-Rogers, Eva

    2016-01-01

    Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process. PMID:25772116

  6. Point-of-care monitoring of oral anticoagulation therapy in children. Comparison of the CoaguChek XS system with venous INR and venous INR using an International Reference Thromboplastin preparation (rTF/95).

    PubMed

    Greenway, Anthea; Ignjatovic, Vera; Summerhayes, Robyn; Newall, Fiona; Burgess, Janet; DeRosa, Lydia; Monagle, Paul

    2009-07-01

    Point-of-care (POC) monitoring of oral anticoagulation has been widely adopted in both paediatric and adult patients. A new POC system, the CoaguChek XS has recently been developed to measure the international normalised ratio (INR) and may offer significant advantages. The CoaguChek XS utilises a new method of electrochemical clot detection based on thrombin generation. This system has not been previously evaluated in children with reference to the laboratory gold standard, the prothrombin time using reference thromboplastin. It was the objective to compare values obtained by the CoaguChek XS system with both the venous INR and the gold standard for anticoagulant monitoring, prothrombin time with reference thromboplastin (rTF/95). To evaluate the impact of testing using the CoaguChek XS on clinical anticoagulant dosing decisions. Fifty paired venous INR and capillary CoaguChek XS results were obtained from 31 children (aged up to 16 years). The laboratory gold standard, a manual prothrombin time with reference thromboplastin (rTF/95) was additionally performed on 26 samples. Correlation between the CoaguChek XS result and the venous INR was r = 0.810. Agreement between the CoaguChek XS result and the reference INR was shown to be higher (r=0.95), in the subset analysed by this method. Correlation between the venous INR and reference INR was r=0.90. Despite changes to the methodology of testing with the CoaguChek XS POC monitoring system, the accuracy of this method when compared with both the venous INR and gold standard reference INR was satisfactory. This resulted in infrequent changes to clinical decision making regarding anticoagulation.

  7. The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

    PubMed Central

    Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria

    2016-01-01

    Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3’-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3’-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and

  8. Advances in Oral Coagulants

    PubMed Central

    2013-01-01

    This article reviews current and future treatment practices concerning oral anticoagulants. In the second decade of the 21st millennium clinicians can finally treat thrombotic disease with long-awaited new oral anticoagulant medications. In addition, improvements have been made in managing warfarin, the traditional but far from obsolete medication. The first part of this review will cover current advances with warfarin treatment. The second portion will discuss specific active coagulation factor inhibitors, the new oral anticoagulants.

  9. The SAMe-TT2R2 score and decision-making between a vitamin K antagonist or a non-vitamin K antagonist oral anticoagulant in patients with atrial fibrillation.

    PubMed

    Esteve-Pastor, María Asunción; Roldán, Vanessa; Valdés, Mariano; Lip, Gregory Y H; Marín, Francisco

    2016-01-01

    Oral anticoagulation therapy is essential in patients with atrial fibrillation and clinicians need guidance on decision-making between the vitamin K antagonists (VKA), e.g. warfarin, or non-vitamin K antagonist oral anticoagulants. Observational studies have shown that patients who receive VKA therapy spend a significant percentage of their time with international normalized ratio values outside of the therapeutic range (time in therapeutic range, TTR <60%.) Recently, a clinical score has been developed with commonly encountered clinical features, the SAMe-TT2R2 score, to help decision-making with regard to whether a patient is likely to do well, or not, with a VKA. Those with a SAMe-TT2R2 score of 0-1 are likely to do well on a VKA, while those with a SAMe-TT2R2 score ≥ 2 are on probability going to achieve suboptimal TTR. In this article, we provide an overview of the main published retrospective and prospective studies that have validated the SAMe-TT2R2 score and its value for decision-making in daily clinical practice.

  10. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  11. Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin?

    PubMed

    Arepally, Gowthami M; Ortel, Thomas L

    2015-01-01

    The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come. PMID:25587651

  12. Early real-world evidence of persistence on oral anticoagulants for stroke prevention in non-valvular atrial fibrillation: a cohort study in UK primary care

    PubMed Central

    Johnson, Michelle E; Lefèvre, Cinira; Collings, Shuk-Li; Evans, David; Kloss, Sebastian; Ridha, Essra; Maguire, Andrew

    2016-01-01

    Objectives To examine the characteristics and persistence in patients newly initiated with oral anticoagulants (OACs) for stroke prevention in non-valvular atrial fibrillation (NVAF). Design Cohort study in Clinical Practice Research Datalink. Setting UK primary care. Participants 15 242 patients with NVAF newly prescribed apixaban, rivaroxaban, dabigatran or vitamin K antagonists (VKAs) between 1 December 2012 and 31 October 2014. 13 089 patients were OAC naïve. Outcome measures Patient characteristics and risk of non-persistence compared to apixaban using Cox regression models over the entire follow-up and using a time-partitioned approach to handle non-proportional hazards. Results Among the OAC naïve patients, VKAs were most common (78.1%, n=10 218), followed by rivaroxaban (12.1%, n=1589), dabigatran (5.7%, n=741) and apixaban (4.1%, n=541). High baseline stroke risk (CHA2DS2VASc ≥2) ranged from 80.2% (dabigatran) to 88.4% (apixaban and rivaroxaban). History of stroke and bleeding was the highest among apixaban (23.7% and 31.6%) and lowest among VKA patients (15.9% and 27.5%). Across the entire follow-up period, adjusting for differences in characteristics, there was no evidence of a difference in non-persistence between VKA and apixaban (HR 0.92 (95% CI 0.68 to 1.23)). Non-persistence was higher with dabigatran (HR 1.67 (1.20 to 2.32)) and rivaroxaban (HR 1.41 (1.02 to 1.93)) than apixaban. Using the partitioned approach, non-persistence was lower with VKA (HR 0.33 (0.22 to 0.48)), and higher with dabigatran (HR 1.65 (1.08 to 2.52)) compared to apixaban in the first 2 months of follow-up. After 2 months, non-persistence was higher with VKA (HR 1.70 (1.08 to 2.66)) and dabigatran (HR 2.10 (1.30 to 3.41)). Pooling OAC naïve and experienced patients, non-persistence was also higher with rivaroxaban compared to apixaban after 2 months of follow-up (HR 1.69 (1.19 to 2.39)). Conclusions Observed differential prescribing of OACs can result in

  13. [Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors. Proposals of the Working Group on Perioperative Haemostasis (GIHP) - March 2013].

    PubMed

    Pernod, G; Albaladejo, P; Godier, A; Samama, C M; Susen, S; Gruel, Y; Blais, N; Fontana, P; Cohen, A; Llau, J V; Rosencher, N; Schved, J F; de Maistre, E; Samama, M M; Mismetti, P; Sié, P

    2013-10-01

    New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis.

  14. 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.

  15. Adherence to oral anticoagulants in patients with atrial fibrillation—a population-based retrospective cohort study linking health information systems in the Valencia region, Spain: a study protocol

    PubMed Central

    Sanfélix-Gimeno, G; Rodríguez-Bernal, C L; Hurtado, I; Baixáuli-Pérez, C; Librero, J; Peiró, S

    2015-01-01

    Introduction Adherence to oral anticoagulation (OAC) treatment, vitamin K antagonists or new oral anticoagulants, is an essential element for effectiveness. Information on adherence to OAC in atrial fibrillation (AF) and the impact of adherence on clinical outcomes using real-world data barely exists. We aim to describe the patterns of adherence to OAC over time in patients with AF, estimate the associated factors and their impact on clinical events, and assess the same issues with conventional measures of primary and secondary adherence—proportion of days covered (PDC) and persistence—in routine clinical practice. Methods and analysis This is a population-based retrospective cohort study including all patients with AF treated with OAC from 2010 to date in Valencia, Spain; data will be obtained from diverse electronic records of the Valencia Health Agency. Primary outcome measure: adherence trajectories. Secondary outcomes: (1) primary non-adherence; (2) secondary adherence: (a) PDC, (b) persistence. Clinical outcomes: hospitalisation for haemorrhagic or thromboembolic events and death during follow-up. Analysis: (1) description of baseline characteristics, adherence patterns (trajectory models or latent class growth analysis models) and conventional adherence measures; (2) logistic or Cox multivariate regression models, to assess the associations between adherence measures and the covariates, and logistic multinomial regression models, to identify characteristics associated with each trajectory; (3) Cox proportional hazard models, to assess the relationship between adherence and clinical outcomes, with propensity score adjustment applied to further control for potential confounders; (4) to estimate the importance of different healthcare levels in the variations of adherence, logistic or Cox multilevel regression models. Ethics and dissemination This study has been approved by the corresponding Clinical Research Ethics Committee. We plan to disseminate the

  16. Anticoagulation in the Elderly

    PubMed Central

    Robert-Ebadi, Helia; Righini, Marc

    2010-01-01

    Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future.

  17. 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

  18. Anticoagulation in patients with impaired renal function and with haemodialysis. Anticoagulant effects, efficacy, safety, therapeutic options.

    PubMed

    Harenberg, J; Hentschel, V A-T; Du, S; Zolfaghari, S; Krämer, R; Weiss, C; Krämer, B K; Wehling, M

    2015-01-01

    Patients with impaired renal function are exposed to an increased risk for bleeding complications depending on the amount of the anticoagulant eliminated by the kidneys. The elimination of unfractionated heparins, vitamin K antagonists and argatroban is only minimally influenced by a reduced renal function. Low-molecular weight heparins, fondaparinux, danaparoid, hirudins and non-vitamin K antagonist oral anticoagulants (NOAC) cause a variably increased bleeding risk in renal impairment. Dose reductions are recommended for all of these anticoagulants in renal impairment, some are even contraindicated at certain levels of renal impairment. Their benefit over the conventional anticoagulants is preserved if renal dosing is employed. For end-stage renal disease patients specific treatment regimens are required. PMID:25405246

  19. New anticoagulants: pharmacology and clinical studies.

    PubMed

    Samama, Charles Marc

    2011-02-01

    The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard. PMID:21404139

  20. New anticoagulants: pharmacology and clinical studies.

    PubMed

    Samama, Charles Marc

    2011-02-01

    The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard.

  1. [Extended options of anticoagulant treatment in thromboembolism].

    PubMed

    Karetová, Debora; Bultas, Jan

    2014-11-01

    Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment. In mid 2014, 3 drugs of this group are registered in Czech Republic - rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®). These drugs have comparable efficacy and safety but they differ in schedule of dose administration. Rivaroxaban and apixaban can be administered immediately after diagnosis of venous thrombosis or hemodynamically stable pulmonary embolism. LMWH application has to precede few days the administration of dabigatran. Limitation of new drugs is their price. Unavailability of antidotes is temporary because current researches continue to find one for dabigatran and another for both of xabans. Duration of anticoagulant treatment after acute phase depends on the presence of thrombosis risk factors and the individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months, commonly 6-12 months and in high risk patients it is "long term" treatment. Good results of new anticoagulant drugs in trials in term of thromboembolism recurrence prevention may change established habits in TD patients with long term treatment. PMID:25600045

  2. Review: anticoagulation for haemodialysis.

    PubMed

    Suranyi, Michael; Chow, Josephine S F

    2010-06-01

    The coagulation cascade is complex but well studied. Dialysis membranes and lines are inherently pro-coagulant and activate both the intrinsic and extrinsic pathways of coagulation, as well as platelets and other circulating cellular elements. To provide safe and effective dialysis, appropriate anticoagulant measures must be applied. Haemodialysis, including anticoagulation, is prescribed by dialysis doctors but delivered by dialysis nurses. The main agents used in clinical practice for anticoagulation during haemodialysis are unfractionated heparin (UF heparin) and low-molecular-weight heparin (LMWH). LMWH has a number of potential advantages, apart from cost. One of the most serious complications of the use of any form of heparin is heparin-induced thrombocytopaenia (HIT) Type II, which occurs more commonly with UF heparin than LMWH. HIT Type II risks severe morbidity and mortality and is challenging to treat successfully in both the acute and chronic phase. In HIT Type II anticoagulation must be delivered without heparin. A wide array of newer anticoagulants are becoming progressively available, each with unique advantages and disadvantages. In maintenance haemodialysis patients with an increased risk of bleeding, a 'no heparin' dialysis may be undertaken, or regional anticoagulation considered. Because this aspect of dialysis is so important to the safe and effective delivery of haemodialysis therapy, dialysis clinicians need to review and update their knowledge of dialysis anticoagulation on a regular basis. PMID:20609088

  3. New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

    PubMed Central

    McRae, Simon J; Ginsberg, Jeffrey S

    2005-01-01

    Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety), ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism. PMID:17319097

  4. 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.

  5. Are we at the goal line with the novel oral anticoagulants and have we reached the end of the line for dronedarone and vernakalant--or is there more to come?

    PubMed

    Reiffel, James A

    2014-11-01

    The authors of this Mini-Hot-Topic collection of review manuscripts have provided an outstanding review of the development and current status of several of our most recently developed agents in the fight against atrial fibrillation (AF). They have also given the readers a glimpse into the difficulty of drug development and the contrasts that can exist with the same product in different geographies. For their efforts they have my deepest appreciation. It is my hope that these articles will assist those of you who are clinicians in your care of patients and those of you who are investigators in your appreciation of the drug development process and its hurdles. More specifically, this Mini-Hot-Topic symposium has reviewed for you: (1) the evidence supporting the new novel oral anticoagulants (NOACs) as first-line therapy for prevention of stroke and systemic embolism in patients with "nonvalvular" atrial fibrillation (NVAF); (2) the winding path taken by dronedarone in reaching its current place in our antiarrhythmic armamentarium - in which it still has a role; and (3) the contrasting decisions made with respect to the marketing of vernakalant in Europe versus the United States. Now, in this last manuscript of the collection, I will echo for emphasis some of their highlights and I will also bring you further up to date with respect to a possible future role for dronedarone, as hinted at by the HARMONY trial. PMID:25004988

  6. A systematic review on the use of new anticoagulants in pregnancy

    PubMed Central

    Tang, Ai-Wei; Greer, Ian

    2013-01-01

    New anticoagulants such as direct factor Xa inhibitors and direct thrombin inhibitors have been recently developed, but their experience in pregnancy is limited. This review therefore aims to systematically search for studies on the use of these newer anticoagulants in pregnancy and the puerperal period. Searches were performed on electronic databases MEDLINE (from 1966), EMBASE (from 1974) and the Cochrane Library, until October 2011 using terms of ‘pregnancy’, ‘puerperium’, ‘breastfeeding’ and names of specific anticoagulants. The search yielded 561 citations and 11 studies (10 on fondaparinux, 1 on ximelagatran) were included. Newer anticoagulants (fondaparinux, hirudin and argatroban) on the limited evidence appear not to have adverse pregnancy outcomes, but there is currently no experience of new oral anticoagulants (rivaroxaban, apixaban, betrixaban or dabigatran) use in pregnancy. There is a need for reporting on new oral anticoagulation use in pregnancy to provide more information about the safety and risks to the fetus in utero.

  7. Accessing inpatient rehabilitation after acute severe stroke: age, mobility, prestroke function and hospital unit are associated with discharge to inpatient rehabilitation.

    PubMed

    Hakkennes, Sharon; Hill, Keith D; Brock, Kim; Bernhardt, Julie; Churilov, Leonid

    2012-12-01

    The objective of this study was to identify the variables associated with discharge to inpatient rehabilitation following acute severe stroke and to determine whether hospital unit contributed to access. Five acute hospitals in Victoria, Australia participated in this study. Patients were eligible for inclusion if they had suffered an acute severe stroke (Mobility Scale for Acute Stroke ≤ 15). Physiotherapists assessed patients on day 3 poststroke, collecting demographic information and information relating to their prestroke status, social status and current status. Stepwise logistic-regression modelling was used to examine the association between age, type of stroke, prestroke living situation, comorbidities, availability of carer on discharge, current mobility, bladder continence, bowel continence, cognition and communication and the dependent variable, discharge destination (rehabilitation/other). The resulting model was analysed using hierarchical logistic regression with hospital unit as the clustering variable. Of the 108 patients fulfilling the inclusion criteria, 70 (64.8%) were discharged to rehabilitation. The variables independently associated with discharge to rehabilitation were younger age [odds ratio (OR)=0.89, 95% confidence interval (CI)=0.83-0.95, P=0.001], independent premorbid functional status (OR=14.92, 95% CI=2.43-91.60, P=0.004) and higher level of current mobility (OR=1.31, 95% CI=1.02-1.66, P<0.03). The multilevel model estimated that 12% of the total variability in discharge destination was explained by differences between the hospital units (ρ=0.12, 95% CI=0.02-0.55, P=0.048). The results indicate that the variables associated with discharge to rehabilitation following severe stroke are younger age, independent prestroke functional status and higher level of current mobility. In addition, organizational factors play a role in selection for rehabilitation, suggesting inequity in access for this patient group. PMID:22728683

  8. [Duration of anticoagulant therapy in venous thromboembolic complications].

    PubMed

    Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A

    2016-01-01

    Adequate anticoagulant therapy is a general approach to treatment of deep vein thrombosis. However, the duration of anticoagulant therapy is not strictly specified in everyday clinical practice. The present article deals with various approaches to selecting the duration of therapy with anticoagulants based on the findings of studies, national and foreign clinical guidelines. The minimal duration of therapy for deep vein thrombosis and pulmonary thromboembolism amounts to 3 months in accordance with the national and American recommendations. For some cohorts of patients, continuation of therapy above 3 months is considered: patients with idiopathic thrombosis (the recommended duration of therapy of not less than 6 months), patients having persisting risk factor for relapse of thrombosis on termination of the main therapeutic course, oncological patients (6 month therapy followed by assessing the risk and benefit of continuing therapy with anticoagulants). Prolonged therapy of venous thromboembolism using unfractionated heparin or low-molecular-weight heparin followed by changing over to vitamin K antagonists is associated with decreased risk for thrombosis relapse approximately by 90%, however increasing the risk of haemorrhage. Currently, as an alternative, it is possible to consider administration of novel oral anticoagulants (rivaroxaban, dabigatran, apixaban) which beside high efficacy are associated with less risk of bleeding. The route of administration, no necessity to control the INR, and the minimal number of drug and food interactions make administration of new oral anticoagulants an attractive alternative to therapy with heparins and vitamin K antagonists.

  9. [Duration of anticoagulant therapy in venous thromboembolic complications].

    PubMed

    Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A

    2016-01-01

    Adequate anticoagulant therapy is a general approach to treatment of deep vein thrombosis. However, the duration of anticoagulant therapy is not strictly specified in everyday clinical practice. The present article deals with various approaches to selecting the duration of therapy with anticoagulants based on the findings of studies, national and foreign clinical guidelines. The minimal duration of therapy for deep vein thrombosis and pulmonary thromboembolism amounts to 3 months in accordance with the national and American recommendations. For some cohorts of patients, continuation of therapy above 3 months is considered: patients with idiopathic thrombosis (the recommended duration of therapy of not less than 6 months), patients having persisting risk factor for relapse of thrombosis on termination of the main therapeutic course, oncological patients (6 month therapy followed by assessing the risk and benefit of continuing therapy with anticoagulants). Prolonged therapy of venous thromboembolism using unfractionated heparin or low-molecular-weight heparin followed by changing over to vitamin K antagonists is associated with decreased risk for thrombosis relapse approximately by 90%, however increasing the risk of haemorrhage. Currently, as an alternative, it is possible to consider administration of novel oral anticoagulants (rivaroxaban, dabigatran, apixaban) which beside high efficacy are associated with less risk of bleeding. The route of administration, no necessity to control the INR, and the minimal number of drug and food interactions make administration of new oral anticoagulants an attractive alternative to therapy with heparins and vitamin K antagonists. PMID:27100556

  10. Surgery and invasive procedures in patients on long-term treatment with direct oral anticoagulants: thrombin or factor-Xa inhibitors. Recommendations of the Working Group on Perioperative Haemostasis and the French Study Group on Thrombosis and Haemostasis.

    PubMed

    Sié, Pierre; Samama, Charles M; Godier, Anne; Rosencher, Nadia; Steib, Annick; Llau, Juan V; Van der Linden, Philippe; Pernod, Gilles; Lecompte, Thomas; Gouin-Thibault, Isabelle; Albaladejo, Pierre

    2011-12-01

    Direct oral anticoagulants (DOAs)--inhibitors of thrombin or factor-Xa--are expected to replace vitamin K antagonists in most of their indications. Patients receiving long-term treatment with DOAs are likely to be exposed to elective or emergency surgery or invasive procedures. Owing to the present lack of experience in such conditions, we cannot make recommendations, but only propose perioperative management for optimal safety regarding the risk of bleeding and thrombosis. DOAs may increase surgical bleeding, they have no validated antagonists, they cannot be monitored by simple standardized laboratory assays and their pharmacokinetics vary significantly between patients. Although DOAs differ in many respects, the proposals in the perioperative setting need not be specific to each. For procedures with low haemorrhagic risk, a therapeutic window of 48 hours (last administration 24 hours before surgery, restart 24 hours after) is proposed. For procedures with medium or high haemorrhagic risk, we suggest stopping DOAs 5 days before surgery to ensure complete elimination in all patients. Treatment should be resumed only when the risk of bleeding has been controlled. In patients at high thrombotic risk (e.g. those in atrial fibrillation with a history of stroke), bridging with heparin (low molecular-weight heparin, or unfractionated heparin, if the former is contraindicated) is proposed. In an emergency, the procedure should be postponed for as long as possible (minimum 1-2 half-lives) and non-specific antihaemorrhagic agents, such as recombinant human activated factor VIIa or prothrombin complex concentrates should not be given for prophylactic reversal due to their uncertain benefit-risk. PMID:22152517

  11. [Anticoagulation for patients with non-valvular atrial fibrillation].

    PubMed

    Mizoguchi, Tadataka; Yasaka, Masahiro

    2016-04-01

    Non-valvular atrial fibrillation (NVAF) is the most common cardiac source of emboli in cardioembolic stroke which occupies from 1/4 to 1/3 of acute brain infarction in Japan. Non-vitamin K antagonist oral anticoagulants (NOAC) have been used widely because they are easy to use, their effect in preventing ischemic stroke is higher than or as high as warfarin, their incidence of major hemorrhage is lower than or as low as warfarin, and their incidence of intracranial hemorrhage is much lower than warfarin. However, there seem several issues to address regarding NOAC treatment, such as reversal of anticoagulation, antidotes, monitoring of anticoagulation, rt-PA treatment for acute stroke patients treated with NOACs. In this review, current strategies and issues of anticoagulation for prevention of stroke in NVAF are discussed. PMID:27333751

  12. Anticoagulant therapy in pediatrics

    PubMed Central

    Dabbous, Mariam K.; Sakr, Fouad R.; Malaeb, Diana N.

    2014-01-01

    Thromboembolic episodes are disorders encountered in both children and adults, but relatively more common in adults. However, the occurrence of venous thromboembolism and use of anticoagulants in pediatrics are increasing. Unfractionated Heparin (UH) is used as a treatment and prevention of thrombosis in adults and critically ill children. Heparin utilization in pediatric is limited by many factors and the most important ones are Heparin Induced Thrombocytopenia (HIT) and anaphylaxis. However, Low Molecular Weight Heparin (LMWH) appears to be an effective and safe alternative treatment. Hence, it is preferred over than UH due to favorable pharmacokinetic and side effect profile. Direct Thrombin Inhibitors (DTI) is a promising class over the other anticoagulants since it offers potential advantages. The aim of this review is to discuss the differences between adult and pediatric thromboembolism and to review the current anticoagulants in terms of pharmacological action, doses, drug reactions, pharmacokinetics, interactions, and parameters. This review also highlights the differences between old and new anticoagulant therapy in pediatrics. PMID:25031496

  13. Regulatory Impact on Thrombosis Treatment, Prevention, and Anticoagulant Use.

    PubMed

    Dannemiller, Robert; Ward, Tucker; Fanikos, John

    2016-10-01

    Thromboembolism afflicts millions of patients annually in the United States and is associated with a significant cost burden. Oral anticoagulants provide clinicians with options for management of these diseases and their use continues to grow. Accordingly, regulatory, legislative, and nonprofit organizations have set performance standards with the goal of improving patient outcomes, ensuring patient safety, and reducing costs. Recent efforts in quality improvement have introduced changes surrounding regulatory requirements, surveillance, litigation, and oversight that clinicians should be familiar with. This article summarizes key updates related to the management of anticoagulant therapy as it relates to thrombosis prevention and treatment. PMID:27637311

  14. Usefulness of transoesophageal echocardiography before cardioversion in patients with atrial fibrillation and different anticoagulant regimens

    PubMed Central

    Maltagliati, A; Galli, C A; Tamborini, G; Calligaris, A; Doria, E; Salehi, R; Pepi, M

    2006-01-01

    Objectives To evaluate the prevalence of atrial thrombi in patients with atrial fibrillation undergoing different anticoagulation regimens before cardioversion; to evaluate the usefulness of transoesophageal echocardiography (TOE) guided cardioversion to prevent thromboembolic complications; and to correlate the presence of atrial thrombi with clinical and echocardiographic data. Methods 757 consecutive patients admitted as candidates for cardioversion of atrial fibrillation were enrolled in the study. They were divided into four groups: effective conventional oral anticoagulation, short term anticoagulation, ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective oral anticoagulation with a duration of < 3 weeks for various clinical reasons. All patients underwent TOE before cardioversion; in the presence of atrial thrombi or extreme left atrial echo contrast, cardioversion was postponed. The incidence of thromboembolic events was evaluated after cardioversion. Results Atrial thrombi were detected in 48 of the 757 (6.3%) patients. No significant differences in the percentage of atrial thrombosis were found in the four study groups. Patients with atrial thrombosis were older and had a higher percentage of mitral prosthetic valves, lower left ventricular ejection fraction, more severe atrial spontaneous echo contrast, and lower Doppler left atrial appendage velocities. 648 patients were scheduled for cardioversion. Cardioversion was successful in 89% of patients without any major thromboembolic event. Conclusions The prevalence of atrial thrombosis before cardioversion despite different treatments with anticoagulants is about 7% and a TOE guided approach may prevent the risk of embolic events. PMID:16284221

  15. Treatment of Venous Thromboembolism With New Anticoagulant Agents.

    PubMed

    Becattini, Cecilia; Agnelli, Giancarlo

    2016-04-26

    Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE. PMID:27102510

  16. [New anticoagulants for stroke prevention in atrial fibrillation].

    PubMed

    Diener, H C; Hajjar, K; Frank, B; Perrey, M

    2012-06-01

    Oral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention for patients with atrial fibrillation (AF), yielding a 60-70% relative reduction in stroke risk compared with placebo and a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. This review describes the current landscape and developments in stroke prevention in patients with AF with special reference to secondary prevention. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for these new agents including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF. The new anticoagulants add to the therapeutic options for patients with AF and offer a number of advantages over warfarin for both clinician and patient, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision-making. PMID:22539096

  17. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived.

  18. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived. PMID:26945262

  19. Apixaban and oral implications

    PubMed Central

    Bagán, Jose V.

    2015-01-01

    Background Thrombotic disorders remain a leading cause of death in the Western world, and in this regard a number of anticoagulation treatment have been used, including heparins, fondaparinux, vitamin K antagonists (warfarin, acenocoumarol), and new oral anticoagulants such as apixaban. For years there has been great controversy regarding the use of anticoagulants in planning dental treatments that imply bleeding. The main concerns about using new oral anticoagulants in invasive dental procedures are bleeding due to the lack of an antidote, and the thrombotic risk of the disease for which anticoagulation was indicated in the first place. Material and Methods A literature search was conducted through May 2014 using the keyword “apixaban” for publications in the ISI Web of Knowledge. The search was extended to other databases (PubMed, Scopus and the Cochrane Library). Results Based on the results of the different studies, apixaban seems to be a good alternative to conventional anticoagulation and a reasonable treatment option, though its main and most common adverse effect is bleeding. Dose adjustment is needed in some patients, though regular laboratory monitoring is not required. The use of the drug in different patient populations will define its final indications and doses. Conclusions Regarding the use of apixaban in the dental setting, there is a compelling need for further clinical studies in order to establish more evidence-based guidelines for patients requiring antithrombotic treatment. Key words:Apixaban, dental treatment, dental implications. PMID:26535102

  20. Emerging anticoagulant therapies for atrial fibrillation: new options, new challenges.

    PubMed

    Mangiafico, R A; Mangiafico, M

    2012-01-01

    Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with an increased risk of stroke and systemic embolism. Oral anticoagulation with vitamin K antagonists (VKAs), such as warfarin, has historically been the mainstay of long-term thromboprophylaxis in AF patients. However, although highly effective, VKAs have a number of limitations that make their use difficult and cumbersome in clinical practice. They have a slow onset and offset of action, narrow therapeutic window, marked dose-response variability, and multiple food and drug interactions, and require frequent coagulation monitoring and dose adjustments. To overcome VKA drawbacks, several new oral anticoagulants have been recently developed for use in AF, and three of them, the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban, have completed phase III trials. New agents have proven to be noninferior or superior to warfarin for AF-related stroke prevention, with similar or better safety profiles. These new drugs, with their predictable anticoagulant effect that allows for fixed dosing with no need for coagulation monitoring, have the potential to greatly simplify anticoagulation therapy for AF. Dabigatran etexilate and rivaroxaban are already approved in the United States and Europe for stroke prevention in nonvalvular AF, and dabigatran etexilate has entered current AF guidelines as an alternative to warfarin. However, some issues with new compounds are still unresolved, such as the lack of antidotes and standardized tests to measure drug activity. Active postmarketing monitoring surveillance of effectiveness and safety is required in the implementation of new anticoagulant therapies. PMID:22830344

  1. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients.

    PubMed

    Alings, Marco

    2016-08-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088

  2. Thromboembolism and anticoagulation after Fontan surgery.

    PubMed

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521

  3. [Progress of anticoagulation therapy in atrial fibrillation].

    PubMed

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-01

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.

  4. Thromboembolism and anticoagulation after Fontan surgery.

    PubMed

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict.

  5. Thromboembolism and anticoagulation after Fontan surgery

    PubMed Central

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521

  6. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

    PubMed Central

    2016-01-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088

  7. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

    PubMed Central

    2016-01-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations.

  8. Thromboembolism and anticoagulation after Fontan surgery

    PubMed Central

    Viswanathan, Sangeetha

    2016-01-01

    This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict.

  9. Assessing patients’ anticoagulation preferences for the treatment of cancer-associated thrombosis using conjoint methodology

    PubMed Central

    Noble, Simon; Matzdorff, Axel; Maraveyas, Anthony; Holm, Majbrit V.; Pisa, Giovanni

    2015-01-01

    Low molecular weight heparins have demonstrated superiority over coumarins in the extended treatment of cancer-associated thrombosis and are recommended as first-line therapy in clinical guidelines. Non-vitamin K oral antagonists are yet to be evaluated against low molecular weight heparin for this indication. Nevertheless, a perception that patients favor oral anticoagulants over injections may lead to an increased prescribing of warfarin or non-vitamin K oral antagonists despite the evidence gap. There has been no evaluation of cancer patient preferences for anticoagulants and whether such an evidence gap is an acceptable trade-off for patients prescribed orals. We conducted a study to assess what features are most important to CAT patients regarding their choice of anticoagulant. Two modules were applied: Initial in-depth interviews with 9 patients diagnosed with cancer-associated thrombosis, and thereafter quantitative research, where a further 100 patients completed a choice-based-conjoint exercise, where 15 different scenarios were presented to identify the most important attributes of an anticoagulant. Seventy percent of the patients were treated with injected medication (low molecular weight heparin) and 30% with oral medications. Patients most valued an anticoagulant with minimal interference with their cancer treatment (39%), low thrombosis recurrence rate (24%), and low risk of major bleed (19%). Preference for oral administration over injection had moderate importance (13%). The results show that patients prefer an anticoagulant that does not interfere with their cancer treatment, suggesting the primacy of the cancer disease over venous thromboembolism in these patients. Patients also favor efficacy and safety over convenience of route of administration. PMID:26294737

  10. Longest Event-Free Survival without Anticoagulation in a Mechanical Aortic Valve Replacement

    PubMed Central

    Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald

    2016-01-01

    Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922

  11. Anticoagulation in Atrial Fibrillation – Current Concepts

    PubMed Central

    Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John

    2015-01-01

    This article presents the current status of the use of anticoagulation for the treatment of AF, particularly with the use of non-vitamin K-dependent anticoagulants. Comparisons between these agents and warfarin are made and methods for assessment of anticoagulant activity and reversal are discussed. PMID:26835109

  12. Safe per-operative anticoagulation

    PubMed Central

    Wieberdink, J.

    1967-01-01

    Pre-, per-, and post-operative anticoagulation at the therapeutic level is nowadays the most, if not the only, available effective method to prevent post-operative thrombo-embolism. There is no increased tendency to bleeding to be feared during the operation. The real danger of this prophylaxis consists of a treacherous tendency to acute relative overdosage after the operation. This is explained by the combined indirect action of anticoagulants and influences related to the operation. As its development can accurately be followed by laboratory tests, dangerous levels of anticoagulation can be prevented. Experiences in 242 surgical patients are presented to demonstrate the efficacy of the following post-operative routine: Coagulation studies (prothrombin time or thrombotest) at least twice daily during one week; fractionated administration of anticoagulants and, if necessary, small amounts (0·25-1 mg.) of vitamin K1. The results suggest that with this policy the risk of thrombo-embolism in surgery can be considerably reduced, if not abolished. Images PMID:6076513

  13. [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].

    PubMed

    Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva

    2014-01-01

    There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.

  14. The in-vitro anticoagulant effect of rivaroxaban in neonates.

    PubMed

    Attard, Chantal; Monagle, Paul; Kubitza, Dagmar; Ignjatovic, Vera

    2014-04-01

    The use of anticoagulants in neonates is increasing because of the medical advances improving the long-term survival of very sick infants who are at risk of venous thromboembolism (VTE). Current anticoagulation therapy in neonates is less than ideal, because of the physiological differences compared to children and adults regarding the pathophysiology of thrombosis and pharmacology of the drug. Limitations associated with conventional anticoagulants have prompted the development of novel drugs that specifically target the key proteins in the coagulation system. Rivaroxaban is the first oral, direct Factor Xa inhibitor available for the prevention of VTE in adults. Its predictable pharmacokinetic profile, high oral bioavailability and once-daily dosing make rivaroxaban an optimal anticoagulant that warrants investigation in neonates. This study was designed to determine whether there are age-related differences in the pharmacodynamic effects of rivaroxaban in vitro amongst neonates. Neonatal and adult plasma pools were created and spiked with increasing concentrations of rivaroxaban (0-500 ng/ml). Commercially available prothrombin time (PT), activated partial thromboplastin time (aPTT) and anti-Factor Xa assays as well as a sub-sampling thrombin generation assay were used to measure the rivaroxaban effect. A dose-dependent response was observed for PT, aPTT and lag time in both the age groups. Rivaroxaban caused a significant increase in the clotting time for PT and aPTT as well as an increase in lag time (as measured by thrombin generation) in neonates when compared with adults. In-vivo studies are required to confirm the consistency of dose-response in neonates. PMID:24418940

  15. Improving evidence on anticoagulant therapies for venous thromboembolism in children: key challenges and opportunities.

    PubMed

    Goldenberg, Neil A; Takemoto, Clifford M; Yee, Donald L; Kittelson, John M; Massicotte, M Patricia

    2015-12-10

    Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, and anticoagulant use in this population has become common, despite the absence of US Food and Drug Administration (FDA) approval for this indication. Guidelines for the use of anticoagulants in pediatrics are largely extrapolated from large randomized controlled trials (RCTs) in adults, smaller dose-finding and observational studies in children, and expert opinion. The recently FDA-approved direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, provide potential advantages over oral vitamin K antagonists and subcutaneous low-molecular-weight heparins (LMWHs). However, key questions arise regarding their potential off-label clinical application in pediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHs such as enoxaparin as the mainstay of treatment of pediatric provoked VTE; identify key questions and challenges with regard to DOAC trials and future DOAC therapy in pediatric VTE; and discuss applicable lessons learned from the recent pilot/feasibility phase of a large multicenter RCT of anticoagulant duration in pediatric VTE. The challenges and lessons learned present opportunities to improve evidence for anticoagulant therapies in pediatric VTE through future clinical trials.

  16. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

    PubMed

    Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K

    2016-01-01

    Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

  17. [More with atrial fibrillation, anticoagulants since the coming of NOAK ].

    PubMed

    Forslund, Tomas; von Euler, Mia; Johnsson, Hans; Holmström, Margareta; Wettermark, Björn; Hjemdahl, Paul

    2015-01-01

    Since the introduction of NOAC (non-vitamin K antagonist oral anticoagulants) in 2011 as thromboprophylactic treatment for patients with atrial fibrillation, AF, the number of patients with a diagnosis of atrial fibrillation has increased markedly in our health care registers. The proportion of patients treated with warfarin or NOAC has increased from 47 % to 58 % in 2013. The use of acetylsalicylic acid in patients is decreasing rapidly in patients with AF. NOAC are mostly prescribed by specialists and are mainly used in younger patients with lower CHA2DS2-VASc scores and lower risk for renal insufficiency and bleeding. PMID:25584610

  18. Anticoagulation-associated adverse drug events

    PubMed Central

    Piazza, Gregory; Nguyen, Thanh Nha; Cios, Deborah; Labreche, Matthew; Hohlfelder, Benjamin; Fanikos, John; Fiumara, Karen; Goldhaber, Samuel Z.

    2011-01-01

    Purpose Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a five-year retrospective study at Brigham and Women’s Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated adverse drug events (ADEs). Methods We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women’s Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data regarding the cost associated with hospitalizations in which ADRs occurred. Results Of 463 anticoagulant-associated ADEs, 226 were MEs (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR) followed by pharmacy costs (mean $7,451 per ADR). Conclusion Most anticoagulant-associated ADEs among inpatients result from medication errors and are therefore potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further Quality Improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures. PMID:22114827

  19. [From old to new anticoagulants: the role of the biologist].

    PubMed

    Samama, Mm; Depasse, F

    2009-01-01

    Anticoagulant drugs are of great interest to patients and clinical physicians, as well as research scientists. The latter two groups combine their efforts to unravel the related mechanisms of action, as well as means of monitoring and proper dosing. Unfractionated heparin and low molecular weight heparins and vitamin K antagonists have been on board for several decades by now. They act on several clotting factors in certain sequences. Newer drugs, produced by chemical synthesis, act on a more specific target, often factor Xa or factor IIa. These newer anticoagulants have a great convenience in being orally administered and not needing routing laboratory monitoring - which is their main advantage. Hirudine and fondaparinux have been registered for a few years. This year, that is 2008 + 2009, two of these new anticoagulants have been registered and approved for use in Europe and Canada - these are dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto). Both do not require routine laboratory monitoring. However, coagulation assays for measuring their activity have been studied. A small number of standardized tests should be perfected. PMID:19789124

  20. Efficacy and safety of novel anticoagulants in the elderly

    PubMed Central

    Karamichalakis, Nikolaos; Georgopoulos, Stamatis; Vlachos, Konstantinos; Liatakis, Ioannis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    Atrial fibrillation and venous thromboembolism (VTE) are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of anticoagulants quite challenging. Novel oral anticoagulants (NOACs) have recently emerged as alternatives to Vitamin K Antagonists (VKAs) and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been well-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population. PMID:27781063

  1. Secondary poisoning of owls by anticoagulant rodenticides

    USGS Publications Warehouse

    Mendenhall, V.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

  2. Long-term anticoagulation. Indications and management.

    PubMed Central

    Stults, B M; Dere, W H; Caine, T H

    1989-01-01

    Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs. PMID:2686173

  3. Specific antidotes in development for reversal of novel anticoagulants: a review.

    PubMed

    Gomez-Outes, Antonio; Suarez-Gea, M L; Lecumberri, Ramon; Terleira-Fernandez, Ana I; Vargas-Castrillon, Emilio

    2014-01-01

    In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development. Idarucizumab (BI 655075; Boehringer Ingelheim) is a fragment of an antibody (Fab), which is a specific antidote to the oral direct thrombin inhibitor dabigatran. Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Aripazine (PER-977, ciraparantag; Perosphere Inc.) is a synthetic small molecule (~500 Da) that reverses oral dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH in vivo. These antidotes could provide an alternative for management of life-threatening bleeding events occurring with the above-mentioned anticoagulants. In addition, the specific antidote anivamersen (RB007; Regado Biosciences Inc.) is an RNA aptamer in clinical development to reverse the anticoagulant effect of the parenteral factor IXa inhibitor pegnivacogin, which is also in development. This anticoagulant-antidote pair may provide an alternative in situations in which a fast onset and offset of anticoagulation is needed, like in patients undergoing cardiac surgery with extracorporeal circulation, as an alternative to the heparin/protamine pair. This patent review includes a description of the pharmacological characteristics of the novel specific antidotes, the available results from completed non

  4. Infected renal hematoma complicating anticoagulant therapy.

    PubMed

    Morduchowicz, G; Rabinovitz, M; Neuman, M; Pitlik, S

    1987-03-01

    We describe a case of spontaneous infection of a renal hematoma complicating warfarin sodium anticoagulant therapy. The infected hematoma was successfully drained by sonar-guided fine-needle aspiration. All reported cases of renal hematomas complicating anticoagulant therapy are reviewed.

  5. Delivery of Optimized Inpatient Anticoagulation Therapy: Consensus Statement from the Anticoagulation Forum

    PubMed Central

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

    2013-01-01

    Objective 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. Study Selection and Data Extraction 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 consensus opinion of all authors and are endorsed by the Board of Directors of The Anticoagulation Forum, a 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. Data Synthesis Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in eight key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education (7) care transitions, (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. Conclusions Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national

  6. Poly(γ-glutamic acid), coagulation? Anticoagulation?

    PubMed

    Xu, Tingting; Peng, Fang; Zhang, Tao; Chi, Bo; Xu, Hong; Mao, Chun; Feng, Shuaihui

    2016-11-01

    Poly(γ-glutamic acid) (γ-PGA) powder was usually used as hemostatic agent because of its excellent physical properties of water-absorption and water-locking. However, if γ-PGA absorbs enough water, how about its blood compatibility? Here, the other side of the coin was investigated. The anticoagulant properties of γ-PGA were characterized by in vitro coagulation tests, hemolytic assay, platelet adhesion, and platelet activation. Moreover, cytotoxicity experiments of γ-PGA were also carried out by MTT assay. Results indicated that the sufficient water-absorbed γ-PGA has good anticoagulant property and non-cytotoxicity. It means γ-PGA has good anticoagulant property, non-cytotoxicity. If γ-PGA has absorbed enough water, it can be used as an anticoagulation biomaterial. With double effects (coagulation and anticoagulation), the γ-PGA with desirable bioproperties can be readily tailored to cater to various biomedical applications. PMID:27545694

  7. 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.

  8. Fucosylated chondroitin sulfate as a new oral antithrombotic agent.

    PubMed

    Fonseca, Roberto J C; Mourão, Paulo A S

    2006-12-01

    Fucosylated chondroitin sulfate is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of sulfated fucose branches. We have shown that intravascular injection of fucosylated chondroitin sulfate inhibits thrombus formation in a venous and an arterial shunt model in rats. Since this compound resists digestion by enzymes that cleave mammalian glycosaminoglycans, we investigated the possibility that fucosylated chondroitin sulfate might be absorbed after oral administration. In fact, after oral administration of fucosylated chondroitin sulfate to rats, we observed a dose-dependent increase in the plasma anticoagulant activity, as assessed by assays for activated partial thromboplastin time (aPTT) and thrombin time (TT) (about 3- and 5-fold, respectively) and by anti-IIa activity. Furthermore, animals receiving daily oral doses of this glycosaminoglycan showed a decrease in thrombus weight on experimental models of venous and arterial shunt thrombosis. This antithrombotic action clearly has a strong relationship with anticoagulant activity. Similar doses of heparin administered orally had no effect on the plasma anticoagulant activity or on the thrombus weight. Finally, we observed that fucosylated chondroitin sulfate given orally to rats did not modify the bleeding time. Overall, our results indicate that fucosylated chondroitin sulfate is absorbed after oral administration and could become a promising oral anticoagulant.

  9. Anticoagulants

    MedlinePlus

    ... or interactions with other medicines and vitamin or herbal supplements. This information should not be used as medical ... your doctor about every medicine and vitamin or herbal supplement that you are taking, so he or she ...

  10. The use of vitamin K in patients on anticoagulant therapy: a practical guide.

    PubMed

    Hanslik, Thomas; Prinseau, Jacques

    2004-01-01

    Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or

  11. Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

    PubMed

    Amin, Alpesh; Deitelzweig, Steve; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

    2014-01-01

    Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

  12. Adherence to long-term anticoagulation treatment, what is known and what the future might hold.

    PubMed

    Abdou, John K; Auyeung, Vivian; Patel, Jignesh P; Arya, Roopen

    2016-07-01

    Adherence to medication, commonly reported as being 50% in chronic diseases, is of great concern in healthcare. Medication non-adherence is particularly apparent in chronic diseases, where treatment is often preventative and may provide little or no symptomatic relief or feedback for the patient. A lot of research has been undertaken to describe the extent of non-adherence to long-term anticoagulation therapy, particularly with vitamin K antagonists and more recently with direct oral anticoagulants. However, the literature is scarce with respect to describing adherence to anticoagulation in terms of the behavioural aspects that influence medicine use. Utilizing the COM-B (capability, opportunity, motivation and behaviour) psychological model of non-adherence, we present the available evidence, not only in terms of describing the extent of the non-adherence problem, but also describing why patients do not adhere, offering theory-driven and evidence-based solutions to improve long-term adherence to chronic anticoagulation therapy. Lessons learned are not only applicable within the field of anticoagulation but throughout haematology.

  13. [An outpatient clinic measure and control system for anticoagulation levels, CoaguChek XS].

    PubMed

    Romero Guardeño, Araceli; Pérez Lucena, Dolores Amalia

    2009-03-01

    A significant increase during recent years in the number of patients who need Oral Anticoagulant Treatment has meant a greater role for nurses, especially in Primary Health Care Centers, since nurses, along with doctors, are the professionals responsible for treating those patients. This control is carried out by measuring the levels of anticoagulants in the blood, regulating the anticoagulant medicine doses, and providing patients with the essential health education so patients participate in the treatment of their illness. To a large degree, the preponderance of Primary Health Care Centers in the aforementioned control has developed hand-in-hand with the availability of portable, simple and low cost coagulation measuring systems which permit a direct reading of a patient's anticoagulation level with one drop of capillary blood. The objective of this article is introduce the reader to a measuring system appropriate for outpatient clinic control of anticoagulant levels in blood by mans of the CoaguChek XS System, which is described. The authors specify the sample extraction procedure, how to measure coagulant levels, and recommendations to keep in mind while carrying out this procedure. The authors sketch the importance of health education and finally, they describe some advantages and inconveniences this system has.

  14. [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. PMID:25770008

  15. [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.

  16. Anticoagulant modulation of inflammation in severe sepsis.

    PubMed

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-05-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  17. Lupus-anticoagulant testing at NOAC trough levels.

    PubMed

    Ratzinger, Franz; Lang, Mona; Belik, Sabine; Jilma-Stohlawetz, Petra; Schmetterer, Klaus G; Haslacher, Helmuth; Perkmann, Thomas; Quehenberger, Peter

    2016-08-01

    Non-vitamin K antagonist oral anticoagulants (NOAC), including rivaroxaban, apixaban or dabigatran, regularly show relevant effects on coagulation tests, making the interpretation of results difficult. The aim of this study was to evaluate possible interferences of NOACs in trough level concentrations in lupus anticoagulant (LA) testing. Citrate plasma specimens of 30 healthy volunteers were spiked with rivaroxaban, apixaban or dabigatran in four plasma concentration levels at or below trough NOAC levels. The NOAC concentration was measured using dedicated surrogate concentration tests and a stepwise diagnostic procedure for LA-testing was applied using screening, mixing and confirmatory testing. Results were compared to NOAC-free specimens. Starting with a plasma concentration of 12.5 ng/ml, dabigatran-spiked specimens showed significant prolongations in the lupus anticoagulant-sensitive activated partial thromboplastin time (aPTT-LA) as well as in the Dilute Russell viper venom time (dRVVT), leading to 43.3 % false positives in confirmatory testing in the dRVVT. In contrast, rivaroxaban, beginning with 7.5 ng/ml, exclusively affected dRVVT-based tests. In confirmatory tests, 30.0 % of rivaroxaban-spiked specimens showed false positive results. Starting with 18.75 ng/ml apixaban, a significant prolongation of the dRVVT and up to 20.7 % false positives in confirmatory tests were found. In contrast to other NOACs tested, apixaban did not present with a dose-dependent increase of the dRVVT ratio. In conclusion, the rate of false positive results in LA-testing is unacceptably high at expected trough levels of NOACs. Even at plasma concentrations below the LLOQ of commercially available surrogate tests, LA testing is best avoided in patients with NOAC therapy.

  18. Anticoagulation for pediatric mechanical circulatory support.

    PubMed

    Annich, Gail; Adachi, Iki

    2013-06-01

    Extracorporeal life support applications have evolved considerably in recent years. However, the blood-biomaterial interface remains incompletely understood, and management of the acute inflammatory response and coagulation pathways continues to be challenging. At present, the gold standard for anticoagulation is unfractionated heparin. Since the inception of extracorporeal life support, the mainstay for anticoagulation monitoring has been activated clotting time. However, alongside the technological evolution in extracorporeal life support, the methods for monitoring heparin have also become more sophisticated, adding additional layers of complexity to creating an ideal safe protocol for anticoagulation during extracorporeal life support. To address this, the Extracorporeal Life Support Organization has formed an Anticoagulation Task Force to help direct both a consensus statement and potential guidelines within which the multiple monitoring methods can be customized for extracorporeal life support. One key question that remains in the use of these monitoring methods is whether the objective during extracorporeal life support is to anticoagulate the circuit to prevent thrombus formation within the extracorporeal device or whether it is to systemically anticoagulate the patient. This review details all current monitoring methods and highlights how they can be used during pediatric mechanical circulatory support. PMID:23735984

  19. [Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

    PubMed

    Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu

    2015-04-01

    In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes. PMID:25836998

  20. [Anticoagulant therapy in secondary prevention of coronary events].

    PubMed

    Bultas, Jan

    2014-12-01

    Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban). PMID:25692828

  1. Carbon monoxide: Anticoagulant or procoagulant?

    PubMed

    Nielsen, Vance G; Pretorius, Etheresia

    2014-03-01

    Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis. Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α₂-antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide. Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be species specific differences with regard to hemostatic response to carbon monoxide. Carbon monoxide may be a Janus-faced molecule, with potential to attenuate or exacerbate thrombophilic disease.

  2. Periprocedural anticoagulation of patients undergoing pericardiocentesis for cardiac tamponade complicating catheter ablation of atrial fibrillation.

    PubMed

    Lin, Tao; Bai, Rong; Chen, Ying-wei; Yu, Rong-hui; Tang, Ri-bo; Sang, Cai-hua; Li, Song-nan; Ma, Chang-sheng; Dong, Jian-zeng

    2015-01-01

    Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF.

  3. Effective management of acute deep vein thrombosis: direct oral anticoagulants.

    PubMed

    Roussin, A

    2015-02-01

    Deep vein thrombosis (DVT) is a manifestation of venous thromboembolism (VTE) and accounts for most venous thromboembolic events. Although DVT is not directly life-threatening, thrombi in the proximal veins of the leg can embolize to the lungs to form a pulmonary embolism, which may prove rapidly fatal. If untreated, DVT can also lead to significant morbidity, including development of post-thrombotic syndrome. Among many risk factors, surgery, hospitalization, older age and active cancer increase the risk of VTE, and a previous event increases the risk of recurrence. Early detection and effective clot resolution are vital in managing DVT. Conventional approaches to acute treatment of VTE involve initial fast-acting parenteral heparin overlapping with and followed by vitamin K antagonist therapy. However, vitamin K antagonists have a narrow therapeutic window, require regular monitoring, and have multiple food and drug interactions. Results from phase III clinical studies involving direct Factor Xa and IIa inhibitors suggest that these agents provide an alternative therapeutic option that overcomes some of the complications associated with conventional treatment with predictable pharmacological properties and convenient dosing schedules. Analysis of data from the rivaroxaban EINSTEIN studies also suggests that these agents have the potential to improve patient-reported treatment satisfaction and reduce the length of hospital stay compared with conventional therapy. This review considers these treatment options, suitable treatment durations to prevent recurrence, and the management of DVT treatment in challenging patient groups. PMID:24927023

  4. A systematic review and adjusted indirect comparison of oral anticoagulants.

    PubMed

    Cui, Juncheng; Wu, Bei; Liu, Congwei; Li, Zhihong

    2014-11-01

    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Recognize the high risk of postoperative venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. 2. Distinguish the different pharmacological mechanisms of VTE prophylaxis drugs. 3. Delineate the advantages and disadvantages of each VTE prophylaxis drug. 4. Recognize that rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage. Patients undergoing major orthopedic surgery are at high risk for developing postoperative venous thromboembolism (VTE). The authors analyzed the available evidence on the efficacy and safety of dabigatran, apixaban, and rivaroxaban vs low-molecular-weight heparins (LMWHs) as VTE prophylaxis in major orthopedic surgery. Outcomes evaluated included total VTE, deep venous thrombosis (DVT), pulmonary embolism (PE), death, and major bleeding. Rivaroxaban and apixaban are more efficacious than dabigatran and are as safe as dabigatran. Rivaroxaban is as efficacious as apixaban but can increase the risk of hemorrhage. PMID:25361361

  5. Curative effect of mechanical heart valve replacement and anticoagulant therapy after surgery.

    PubMed

    Chuai, J B; Shi, L; Ma, X Y; Wu, D; Kang, K; Jiang, S L

    2016-01-01

    This study was carried out to determine the curative effect of low-intensity anticoagulant therapy by observing the oral administration of warfarin (anticoagulant therapy) on patients who had undergone mechanical heart valve replacement (MHVR) surgery with subsequent anticoagulation complications. Fifty patients who underwent MHVR in the Second Affiliated Hospital of Harbin Medical University and 52 patients in the Cardiovascular Surgery of Daqing Oilfield General Hospital between January 2013 and January 2016 were selected (63 males and 39 females, ages 26-77 years). They took warfarin after treatment and were followed-up by means of outpatient review and telephone after leaving the hospital. The effect of warfarin and the occurrence of anticoagulation complications were analyzed. The operations lasted 230±106 min, extracorporeal circulation for 110±50 min and aorta occlusion for 82±23 min. During post-operation 3 patients developed skin purpura and one patient died. During follow-up we found 3 cases of anemia caused by excessive menstruation, 4 cases of hematuresis, 3 cases of peated epistaxis, 1 case of gastrointestinal bleeding, 1 case of cerebral hemorrhage, 1 case of embolism in the lower limbs and 1 case of cerebral infarction, although they all improved or were totally cured. Therefore, the incidence of complications can be reduced significantly by the correct administration of warfarin as well as timely monitoring of interference factors after MHVR. PMID:27049085

  6. Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position

    PubMed Central

    Ene, Gabriela; Garcia Raso, Aránzazu; Gonzalez-Dominguez Weber, Almudena; Hidalgo-Vega, Álvaro; Llamas, Pilar

    2016-01-01

    Background: The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. Objectives: The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Methods: Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. Results: We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90), mitro-aortic prosthesis (n = 57), and mitral and tricuspid prosthesis (n = 4). The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58) consisting of 44.38 (±42.30) for drug cost, €71.41 (±21.43) for international normalized ratio monitoring, €429.52 (±126.87) for medical visits, €26.31 (±28.38) for rescue medication and €986.53 (±2735.68) for related complications. Conclusion: Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs. PMID:27579168

  7. 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

    2015-04-01

    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. PMID:25835447

  8. 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

    2015-04-01

    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.

  9. 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

  10. Possible unaware intoxication by anticoagulant rodenticide

    PubMed Central

    Dashti-Khavidaki, Simin; Ghaffari, Saba; Nassiri-Toossi, Mohsen; Amini, Mohsen; Edalatifard, Maryam

    2014-01-01

    Superwarfarin toxicity may be a serious problem. It needs high clinical suspicious in patients with bleeding diathesis without hematologic or liver diseases even in patients with apparent negative history of warfarin or other anticoagulant accessibility. Here we reported a patient with a negative history of any medical diseases or drug administration who was referred with generalized ecchymosis. Increased international normalized ratio and decreased vitamin K-dependent coagulation factors were detected in this patient. His hematologic and liver evaluations were normal. Clinical pharmacist emphasis in taking history revealed using anticoagulant rodenticide all over the farm the patient lived in that might result in unaware intoxication in this patient who suffered dementia. PMID:25535623

  11. Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.

    PubMed

    Harenberg, Job

    2016-04-01

    A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs. PMID:27067972

  12. Discovery of transition state factor Xa inhibitors as potential anticoagulant agents.

    PubMed

    Zhu, B Y; Huang, W; Su, T; Marlowe, C; Sinha, U; Hollenbach, S; Scarborough, R M

    2001-06-01

    Factor Xa is an attractive biological target in the discovery and development of either parenteral or orally active anticoagulant agents. Several strategies have been utilized at COR Therapeutics in the pursuit of tri-peptide based transition state mimetic factor Xa inhibitors with high aqueous solubility. Some of these inhibitors have displayed excellent in vitro potency in inhibiting factor Xa in the prothrombinase complex. More importantly, these compounds showed strong in vivo antithrombotic efficacy without significant bleeding complications in several animal thrombosis models. These results demonstrated that small molecule factor Xa inhibitors could be advantageous over Warfarin and LMWH. For the discovery and development of orally active anticoagulant agents, small organic molecules as reversible factor Xa inhibitors were explored. From a medicinal chemistry perspective, significant insight has been gained regarding the in vivo antithrombotic efficacy and pharmacokinetic behaviors of each class of factor Xa inhibitors. This review will focus on the design and discovery of transition state factor Xa inhibitors as potential parenteral anticoagulant agents. Several excellent comprehensive review articles on factor Xa inhibitors have appeared recently [1-4]. PMID:11899247

  13. Novel anticoagulants - an update on the latest developments and management for clinicians treating patients on these drugs.

    PubMed

    Green, Ben; Mendes, Rui Amaral; Van der Valk, Ruben; Brennan, Peter A

    2016-09-01

    There are several novel anticoagulant agents that are being increasingly used as an alternative to warfarin, with these drugs being reported to be at least as effective if not better. Their increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking these drugs. Surprisingly, there is little published in the current literature specific to professionals involved in oral health care. In this review, we provide an overview of these drugs and discuss the management of patients who need an oral procedure based on currently available literature and clinical trials.

  14. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    PubMed Central

    Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo

    2013-01-01

    Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies. PMID:23674896

  15. Spotlight on idarucizumab and its potential for the reversal of anticoagulant effects of dabigatran

    PubMed Central

    Sié, Pierre

    2016-01-01

    Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of stroke in atrial fibrillation. Idarucizumab is a humanized fragment of a monoclonal antibody, which binds dabigatran reversibly with high affinity and, when administered intravenously, immediately neutralizes its anticoagulant effect. It is rapidly cleared by the kidney with captured dabigatran. In Phase I and II trials, no significant adverse events have been reported. Specifically, idarucizumab has no anticoagulant or procoagulant effect by itself. Idarucizumab is currently being evaluated in an ongoing Phase III trial, in patients treated with dabigatran presenting with severe active bleeding or requiring emergency surgery or an invasive procedure and are at high risk of bleeding. The results of the interim analysis confirm the ability of idarucizumab to neutralize dabigatran instantaneously, without rebound effect, except in rare patients with very high baseline levels of anticoagulant. Although not definitely proving clinical efficacy, due to the noncontrolled design of the trial and the heterogeneity of patient conditions, these promising results on an intermediate criterion with strong rationale have led to the approval of idarucizumab for these indications. However, several questions are unresolved. First, activity measurement of dabigatran in blood, useless in current practice, could be useful to guide the treatment and avoid over- or underutilization of the antidote; but so far, it has not been largely available in real time. Second, the translation of anticoagulant neutralization to an effect on mortality and better outcome is highly dependent on the global management of these patients, especially rapid diagnosis, supportive care, and easy access to antidote administration. Although idarucizumab represents a remarkable achievement in drug design and development, whether it will be an

  16. Is percutaneous closure of the left atrial appendage comparable to anticoagulants for atrial fibrillation?

    PubMed

    Uslar, Thomas; Anabalón, Jaime

    2015-01-01

    For most atrial fibrillation patients oral anticoagulation constitutes the standard treatment to prevent stroke. However, they carry a risk of bleeding, which is why alternative treatments have been put into practice, such as percutaneous closure of the left atrial appendage. It is not clear whether this is as effective as the conventional treatment with anticoagulants. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including only one pertinent randomized controlled trial. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded that percutaneous left atrial appendage occlusion may decrease stroke and mortality, but the certainty of the evidence is low. The effect on other outcomes is not clear because the certainty of the evidence is very low. PMID:26335602

  17. Is percutaneous closure of the left atrial appendage comparable to anticoagulants for atrial fibrillation?

    PubMed

    Uslar, Thomas; Anabalón, Jaime

    2015-08-17

    For most atrial fibrillation patients oral anticoagulation constitutes the standard treatment to prevent stroke. However, they carry a risk of bleeding, which is why alternative treatments have been put into practice, such as percutaneous closure of the left atrial appendage. It is not clear whether this is as effective as the conventional treatment with anticoagulants. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including only one pertinent randomized controlled trial. We combined the evidence and generated a summary of findings following the GRADE approach. We concluded that percutaneous left atrial appendage occlusion may decrease stroke and mortality, but the certainty of the evidence is low. The effect on other outcomes is not clear because the certainty of the evidence is very low.

  18. 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. PMID:27561277

  19. New anticoagulants for the prevention of stroke in atrial fibrillation.

    PubMed

    Höchtl, Thomas; Huber, Kurt

    2012-02-01

    Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter-individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non-central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance. PMID:21883447

  20. Dental management of patients receiving anticoagulant and/or antiplatelet treatment

    PubMed Central

    Chaveli-López, Begonya; Gavaldá-Esteve, Carmen

    2014-01-01

    Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important morbidity-mortality. The dental treatment of patients who tend to an increased risk of bleeding due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis, and the optimized management of such patients, are therefore very important issues. Objectives: A study is made of the anticoagulant / antiplatelet drugs currently available on the market, with evaluation of the risks and benefits of suspending such drugs prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and Methods: A literature search was made in the PubMed, Cochrane Library and Scopus databases, covering all studies published in the last 5 years in English and Spanish. Studies conducted in humans and with scientific evidence levels 1 and 2 (metaanalyses, systematic reviews, randomized phase 1 and 2 trials, cohort studies and case-control studies) were considered. The keywords used for the search were: tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol. Results and Conclusions: Many management protocols have been developed, though in all cases a full clinical history is required, together with complementary hemostatic tests to minimize any risks derived from dental treatment. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from dental treatment. Key words:Tooth extraction, oral surgery, hemostasis, platelet

  1. Strategies to Overcome Heparins’ Low Oral Bioavailability

    PubMed Central

    Neves, Ana Rita; Correia-da-Silva, Marta; Sousa, Emília; Pinto, Madalena

    2016-01-01

    Even after a century, heparin is still the most effective anticoagulant available with few side effects. The poor oral absorption of heparins triggered the search for strategies to achieve oral bioavailability since this route has evident advantages over parenteral administration. Several approaches emerged, such as conjugation of heparins with bile acids and lipids, formulation with penetration enhancers, and encapsulation of heparins in micro and nanoparticles. Some of these strategies appear to have potential as good delivery systems to overcome heparin’s low oral bioavailability. Nevertheless, none have reached the market yet. Overall, this review aims to provide insights regarding the oral bioavailability of heparin. PMID:27367704

  2. [Anticoagulation in patients with chronic renal failure].

    PubMed

    Niksic, L; Saudan, P; Boehlen, F

    2006-03-01

    Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn. Danaparoid and thrombin inhibitors should be used mainly in patients suffering from renal failure and heparin-induced thrombocytopenia with regular monitoring of coagulation tests. PMID:16562602

  3. Laboratory studies on patients receiving anticoagulant therapy

    PubMed Central

    Shaw, S.; Pegrum, G. D.; Wolff, S.

    1965-01-01

    An investigation into the laboratory control of anticoagulant therapy is presented. The cases were divided into those in the first few weeks of therapy and those on long-term treatment. Variations in the levels of factors VII and X, and factor IX were assessed. Thromboplastin levels were used to control therapy. These were compared with parallel estimations by Thrombotest and with the levels of the coagulation factors. Thrombotest was found to have no major advantage over thromboplastin. PMID:14304246

  4. Antiplatelet and Anticoagulant Drugs in Interventional Radiology

    SciTech Connect

    Altenburg, Alexander; Haage, Patrick

    2012-02-15

    In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

  5. Tutorial in oral antithrombotic therapy: Biology and dental implications

    PubMed Central

    Fakhri, Hamid R.; Janket, Sok J.; Baird, Alison E.; Dinnocenzo, Richard; Meurman, Jukka H.

    2013-01-01

    Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants. Method: We searched Medline using search terms “antithrombotic”, “antihemostasis” or “anticoagulation” and combined them with the search results of “dental”, “oral surgery” or “periodontal”. We restricted the results to “human” and “English”. Results: The early coagulation cascade, the new cell-based coagulation model, the pharmacokinetics and pharmacodynamics of conventional antithrombotics, and new oral anticoagulants were reviewed. The new direct factor Xa inhibitors and the direct thrombin inhibitor (s), called direct oral anticoagulants (DOAs) have rapid onset of action, fast elimination on cessation, and fewer drug-drug or drug-food interactions than warfarin. However, the lack of antidotes raises concerns that some dental procedures may trigger serious hemorrhagic events. Additionally, careful perioperative withdrawal and resumption protocols for the DOAs are reviewed, because DOAs’ blood levels are dependent on renal function. Also, various reversal strategies in the event of excessive bleedings are summarized. Perioperative management of dental patients taking new DOAs and conventional oral anticoagulants are also discussed. However, the perioperative strategies for DOAs are yet to be validated in randomized trials. Key words:Coagulation cascade, cell-based coagulation model, factor Xa inhibitors, direct thrombin inhibitors, prothrombin complex concentrates. PMID:23524440

  6. Anticoagulation for the Acute Management of Ischemic Stroke

    PubMed Central

    Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan

    2014-01-01

    Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others. PMID:24910565

  7. Embolic Stroke in Cardiomyopathy: Should Patients be Anticoagulated?

    PubMed

    Narang, Akhil; Lang, Roberto M

    2016-05-01

    Despite advances in the treatment of patients with heart failure, mortality is still substantial. Part of this mortality is explained by cardioembolic stroke. Patients with heart failure are predisposed to developing cardioembolic strokes owing to abnormalities in Virchow's triad (endothelial function, relative hypercoagulable state, and static blood flow). Several randomized controlled trials have addressed whether patients with heart failure benefit from anticoagulation. Overall, the results suggest the risk of bleeding with anticoagulation outweighs any small benefit conferred by anticoagulation. PMID:27150169

  8. Menthol reduces the anticoagulant effect of warfarin by inducing cytochrome P450 2C expression.

    PubMed

    Hoshino, Motohiro; Ikarashi, Nobutomo; Tsukui, Makoto; Kurokawa, Asako; Naito, Rina; Suzuki, Midori; Yokobori, Kohsuke; Ochiai, Takumi; Ishii, Makoto; Kusunoki, Yoshiki; Kon, Risako; Ochiai, Wataru; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2014-06-01

    Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2 days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR. PMID:24594507

  9. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art

    PubMed Central

    Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

    2015-01-01

    Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed. PMID:26664901

  10. Cost-Effectiveness of Anticoagulation in Patients with Nonvalvular Atrial Fibrillation with Edoxaban Compared to Warfarin in Germany

    PubMed Central

    Krejczy, Martin; Harenberg, Job; Wehling, Martin; Lip, Gregory Y. H.

    2015-01-01

    We compared the cost-utility analysis for edoxaban at both doses with that of dabigatran at both doses, rivaroxaban, and apixaban (non vitamin K antagonist oral anticoagulants, NOAC) in a German population. Data of clinical outcome events were taken from edoxaban's ENGAGE-AF, dabigatran's RE-LY, rivaroxaban's ROCKET, and apixaban's ARISTOTLE trials. The base-case analyses of a 65-year-old person with a CHADS2 score >1 gained 0.17 and 0.21 quality-adjusted life years over warfarin for 30 mg od and 60 mg od edoxaban, respectively. The incremental cost-effectiveness ratio was 50.000 and 68.000 euro per quality-adjusted life years for the higher and lower dose of edoxaban (Monte Carlo simulation). These findings were also similar to those for apixaban and more cost-effective than the other NOAC regimens. The current market costs for direct oral anticoagulants are high in relation to the quality of life gained from a German public health care insurance perspective. The willingness-to-pay threshold was lowest for 60 mg edoxaban compared to all direct oral anticoagulants and for 30 mg edoxaban compared to dabigatran and rivaroxaban. PMID:25853142

  11. Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation: can we improve the current prescription of anticoagulants?

    PubMed Central

    Annoni, Giorgio; Mazzola, Paolo

    2016-01-01

    Background In elderly patients, especially those older than 80 years, atrial fibrillation (AF) is associated with an almost 25% increased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital (Monza, Italy). Results Compared to patients without AF (n = 1216), those with AF (n = 403) had a higher Charlson Comorbidity Index (3 vs. 2, P < 0.001), number of administered drugs (4 vs. 3, P < 0.001), rate of heart failure (36.5% vs. 12%, P < 0.001) and chronic kidney disease (20.6 vs. 13.2, P < 0.001). Many patients with AF were frail (54%) or pre-frail (29%). Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy (vitamin K antagonists, VKA). New direct oral anticoagulants (DOAs) can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification. PMID:27103917

  12. Contemporary anticoagulation therapy in patients undergoing percutaneous intervention.

    PubMed

    Bhatty, Shaun; Ali, Asghar; Shetty, Ranjith; Sumption, Kevin F; Topaz, On; Jovin, Ion S

    2014-04-01

    The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions.

  13. Contemporary anticoagulation therapy in patients undergoing percutaneous intervention.

    PubMed

    Bhatty, Shaun; Ali, Asghar; Shetty, Ranjith; Sumption, Kevin F; Topaz, On; Jovin, Ion S

    2014-04-01

    The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions. PMID:24506409

  14. The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation

    PubMed Central

    2015-01-01

    START-Register – Survey on anTicoagulated pAtients RegisTer – is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) <30 ml/min]. Moderate renal failure (CrCl 30-59 ml/min) was found in 1265 patients (39.5%). The analysis of the START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure. PMID:26001109

  15. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    PubMed

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  16. Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

    PubMed

    Huber, Kurt; Bates, Eric R; Valgimigli, Marco; Wallentin, Lars; Kristensen, Steen Dalby; Anderson, Jeffrey L; Lopez Sendon, Jose Luis; Tubaro, Marco; Granger, Christopher B; Bode, Christoph; Ohman, Erik Magnus; Steg, Philippe Gabriel

    2014-11-01

    Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio. PMID:25440788

  17. Shortfalls using second-generation anticoagulant rodenticides.

    PubMed

    Borst, G H A; Counotte, G H M

    2002-03-01

    Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide. PMID:12216801

  18. MRI Screening for Chronic Anticoagulation in Atrial Fibrillation

    PubMed Central

    Fisher, Mark

    2013-01-01

    Anticoagulation is highly effective in preventing stroke due to atrial fibrillation, but numerous studies have demonstrated low utilization of anticoagulation for these patients. Assessment of clinicians’ attitudes on this topic indicate that fear of intracerebral hemorrhage (ICH), rather than appreciation of anticoagulation benefits, largely drives clinical decision-making for treatment with anticoagulation in atrial fibrillation. Risk stratification strategies have been used for anticoagulation benefits and hemorrhage risk, but ICH is not specifically addressed in the commonly used hemorrhage risk stratification systems. Cerebral microbleeds are cerebral microscopic hemorrhages demonstrable by brain MRI, indicative of prior microhemorrhages, and predictive of future risk of ICH. Prevalence of cerebral microbleeds increases with age; and cross-sectional and limited prospective studies generally indicate that microbleeds confer substantial risk of ICH in patients treated with chronic anticoagulation. MRI thus is a readily available and appealing modality that can directly assess risk of future ICH in patients receiving anticoagulants for atrial fibrillation. Incorporation of MRI into routine practice is, however, fraught with difficulties, including the uncertain relationship between number and location of microbleeds and ICH risk, as well as cost-effectiveness of MRI. A proposed algorithm is provided, and relevant advantages and disadvantages are discussed. At present, MRI screening appears most appropriate for a subset of atrial fibrillation patients, such as those with intermediate stroke risk, and may provide reassurance for clinicians whose concerns for ICH tend to outweigh benefits of anticoagulation. PMID:24109470

  19. Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

    SciTech Connect

    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.

  20. Assessing prescribing of NSAIDs, antiplatelets, and anticoagulants in Canadian family medicine using chart review.

    PubMed

    Hamilton, Kevin; Davis, Christine; Falk, Jamie; Singer, Alex; Bugden, Shawn

    2016-10-01

    Background Drug-related problems have been identified as a major contributor to emergency room visits, hospitalizations, and death. The most commonly implicated medications are nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelets, and anticoagulants. Considering a significant proportion of these harms are preventable, indicators to identify risky prescribing before they lead to harm have been developed. Objective To examine the prevalence and patterns of potentially inappropriate prescriptions (PIPs) in a primary care population who are using high-risk medications. Setting This study was performed within two multi-disciplinary family medicine teaching clinics in Winnipeg, Canada. Method A cross-sectional electronic/paper chart audit was conducted within two multi-disciplinary family medicine teaching clinics to evaluate the prevalence of 13 evidence-based high-risk prescriptions. Patients were included if they were prescribed an oral NSAID, antiplatelet, or an anticoagulant within the 12 month period between June 2012 and June 2013. Main outcome measure The proportion of PIPs associated with an increased bleeding risk for NSAIDs, antiplatelets, and anticoagulants. Results Of the 567 patients included in the review, 198 (35 %) patients had received at least 1 PIP in the past year. The most common PIP was the use of an oral NSAID with one or more GI risk factors without adequate gastro-protection. Only 34 (6 %) of these patients received a full medication review performed by a pharmacist. Although not statistically significant, patients who received a medication review had fewer inappropriate prescriptions (27 % with review, 35 % without). Conclusion Over one-third of the patients who were using high-risk medications were using them potentially inappropriately. Although pharmacists have been shown to reduce the amount of inappropriate prescribing, very few patients using these medications were referred to the pharmacist for a full medication review

  1. New anticoagulants for the treatment of venous thromboembolism

    PubMed Central

    Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio

    2016-01-01

    Worldwide, venous thromboembolism (VTE) is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context. PMID:27167437

  2. Anticoagulation management during cross-clamping and bypass.

    PubMed

    Lander, H; Zammert, M; FitzGerald, D

    2016-09-01

    Anticoagulation is required for successful implementation of cardiopulmonary bypass (CPB), as well as for surgeries requiring temporary aortic occlusion. It is well established that both coagulation and fibrinolysis are activated during CPB (Teufelsbauer et al., 1992) [1]. Appropriate dosing, monitoring, and maintenance of anticoagulation are essential to prevent devastating thrombosis of the CPB circuit or the occluded aorta and to minimize the activation of the hemostatic system. Although numerous novel anticoagulants have been developed over the past decade, unfractionated heparin remains the primary anticoagulant utilized during these types of procedures, with monitoring systems primarily based upon the activated clotting time and/or heparin concentration. This article will review the current state of anticoagulation management during cross-clamp and CPB. PMID:27650345

  3. Physician's Fear of Anticoagulant Therapy in Nonvalvular Atrial Fibrillation

    PubMed Central

    Dahlberg, Katherine Willett

    2014-01-01

    Abstract: Despite the availability of predictive tools and treatment guidelines, anticoagulant therapies are underprescribed and many patients are undertreated for conditions that predispose to thromboembolic complications, including stroke. This review explores reasons for which physicians fear that the risks of anticoagulation may be greater than the potential benefit. The results of numerous clinical trials confirm that patients benefit from judiciously managed anticoagulation and that physicians can take various approaches to minimize risk. Use of stratification scores for patient selection and accurate estimation of stroke risk may improve outcomes; bleeding risk is less important than stroke risk. Adoption of newer anticoagulants with simpler regimens may help physicians allay their fears of anticoagulant use in patients with atrial fibrillation. These fears, although not groundless, should not overtake caution and hinder the delivery of appropriate evidence-based care. PMID:25285512

  4. Oral contraceptives and the prothrombin time.

    PubMed

    Pangrazzi, J; Roncaglioni, M C; Donati, M B

    1980-02-01

    Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

  5. Anticoagulant Heparan Sulfate: Structural Specificity and Biosynthesis

    PubMed Central

    Liu, Jian; Pedersen, Lars C.

    2007-01-01

    Summary Heparan sulfate (HS) is present on the surface of endothelial and surrounding tissues in large quantities. It plays important roles in regulating numerous functions of the blood vessel wall, including blood coagulation, inflammation response and cell differentiation. HS is a highly sulfated polysaccharide containing glucosamine and glucuronic/iduronic acid repeating disaccharide units. The unique sulfated saccharide sequences of HS determine its specific functions. Heparin, an analogue of heparan sulfate, is the most commonly used anticoagulant drug. Because of its wide range of biological functions, HS has become an interesting molecule to biochemists, medicinal chemists and developmental biologists. Here, we summarize recent progress towards understanding the interaction between heparan sulfate and blood coagulating factors, the biosynthesis of anticoagulant heparan sulfate and the mechanism of action of heparan sulfate biosynthetic enzymes. Further, knowledge of the biosynthesis of HS facilitates the development of novel enzymatic approaches to synthesize HS from bacterial capsular polysaccharides and to produce polysaccharide end products with high specificity for the biological target. These advancements provide the foundation for the development of polysaccharide-based therapeutic agents. PMID:17131147

  6. Comparative risk assessment of the first-generation anticoagulant rodenticide diphacinone to raptors

    USGS Publications Warehouse

    Rattner, Barnett A.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Horak, Katherine E.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Meteyer, Carol U.; Johnson, John J.

    2012-01-01

    New regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides in the United States, and in some situations this action may be offset by expanded use of first-generation compounds. We have recently conducted several studies with captive adult American kestrels and eastern screech-owls examining the toxicity of diphacinone (DPN) using both acute oral and short-term dietary exposure regimens. Diphacinone evoked overt signs of intoxication and lethality in these raptors at exposure doses that were 20 to 30 times lower than reported for traditionally used wildlife test species (mallard and northern bobwhite). Sublethal exposure of kestrels and owls resulted in prolonged clotting time, reduced hematocrit, and/or gross and histological evidence of hemorrhage at daily doses as low as 0.16 mg DPN/kg body weight. Findings also demonstrated that DPN was far more potent in short-term 7-day dietary studies than in single-day acute oral exposure studies. Incorporating these kestrel and owl data into deterministic and probabilistic risk assessments indicated that the risks associated with DPN exposure for raptors are far greater than predicted in analyses using data from mallards and bobwhite. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

  7. Plasma disposition of vitamin K1 in relation to anticoagulant poisoning.

    PubMed Central

    Park, B K; Scott, A K; Wilson, A C; Haynes, B P; Breckenridge, A M

    1984-01-01

    The disposition of vitamin K1, after intravenous (10 mg) and oral doses (10 mg and 50 mg) was studied in six healthy male subjects. After intravenous administration, the plasma concentration-time profile was adequately fitted with an average terminal half-life of 1.7 h. After oral administration (10 mg and 50 mg) the availability of vitamin K showed marked inter-individual variation (10-63%). With the higher dose intra-individual variation was also observed. Experiments in brodifacoum-anticoagulated rabbits demonstrate that the duration of action of a pharmacological dose (10 mg/kg) is short (9 h) and that high plasma concentrations (ca 1 microgram/ml) of the vitamin are required to drive clotting factor synthesis during maximum coumarin anticoagulation. Taken collectively, these data indicate that the short duration of action of vitamin K, frequently observed in cases of coumarin poisoning, is a consequence of requirements for high vitamin K concentrations and rapid clearance of the vitamin. PMID:6508974

  8. Is stopping of anticoagulant therapy really required in a minor dental surgery? - How about in an endodontic microsurgery?

    PubMed Central

    Cho, Yong-Wook

    2013-01-01

    Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery. PMID:24010076

  9. Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation: A Noninterventional Study.

    PubMed

    Tsantes, Argirios E; Kyriakou, Elias; Ikonomidis, Ignatios; Katogiannis, Konstantinos; Papadakis, Ioannis; Douramani, Panagiota; Kopterides, Petros; Kapsimali, Violetta; Lekakis, John; Tsangaris, Iraklis; Bonovas, Stefanos

    2016-04-01

    There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P < 0.001). In LTA, patients on dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P < 0.001), but significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, P = 0.045; Tmax, P = 0.016; and Cmax, P = 0.003).Based on ROTEM and TG assays, the anticoagulant effects induced by the 2 drugs given in the specific dose regimens in real-world patients were comparable. Only platelet aggregation was found to be more affected by dabigatran as compared to rivaroxaban.

  10. Comparative Assessment of the Anticoagulant Activity of Rivaroxaban and Dabigatran in Patients With Nonvalvular Atrial Fibrillation: A Noninterventional Study.

    PubMed

    Tsantes, Argirios E; Kyriakou, Elias; Ikonomidis, Ignatios; Katogiannis, Konstantinos; Papadakis, Ioannis; Douramani, Panagiota; Kopterides, Petros; Kapsimali, Violetta; Lekakis, John; Tsangaris, Iraklis; Bonovas, Stefanos

    2016-04-01

    There is a shortage of data in everyday clinical practice about the anticoagulant effects caused by the new oral anticoagulants (NOAs). Our aim was to estimate the intensity of anticoagulant activity induced by rivaroxaban 20 mg qd and dabigatran 110 mg bid among patients with nonvalvular atrial fibrillation (NV-AF).We studied 20 patients with NV-AF treated with dabigatran, and 20 patients treated with rivaroxaban. We performed conventional coagulation tests, thrombin generation (TG) test, thromboelastometry (ROTEM), and epinephrine-induced light transmission aggregometry (LTA) in all 40 patients and 20 controls. Hemoclot Thrombin Inhibitors (HTI) and Factor Xa Direct Inhibitor (DiXaI) assay were used to measure dabigatran and rivaroxaban plasma levels, respectively.Measurements of all assays estimating anticoagulant activity across the 2 patient groups were similar, except for aPTT. Patients on dabigatran exhibited statistically significantly prolonged aPTT values (P < 0.001). In LTA, patients on dabigatran also showed decreased aggregation compared to those on rivaroxaban (P = 0.045). Regarding the TG test, there was no association between endogenous thrombin potential (ETP) and rivaroxaban plasma levels (P = 0.33) as opposed to dabigatran levels (P < 0.001), but significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, P = 0.045; Tmax, P = 0.016; and Cmax, P = 0.003).Based on ROTEM and TG assays, the anticoagulant effects induced by the 2 drugs given in the specific dose regimens in real-world patients were comparable. Only platelet aggregation was found to be more affected by dabigatran as compared to rivaroxaban. PMID:27057830

  11. Risk factors for the effect of anticoagulant and antiplatelet agents on perioperative blood loss following proximal femoral fractures.

    PubMed

    Akaoka, Yusuke; Yamazaki, Hiroshi; Kodaira, Hiroyuki; Kato, Hiroyuki

    2016-07-01

    To examine the effect of oral anticoagulant and antiplatelet agents on perioperative blood loss following proximal femoral fractures and to identify the risk factors associated with perioperative blood loss.Retrospective cross-sectional study.In a retrospective cross-sectional study, we treated 334 consecutive patients with proximal femoral fractures (100 who received anticoagulant or antiplatelet drugs and 234 who did not) and an overall mean age of 85.5 years (standard deviation 8.2 years). We performed retrospective multivariate analysis to determine the independent factors related to perioperative decreases in the hemoglobin (Hb) level, a proxy for blood loss.Multivariate analysis confirmed that anticoagulant or antiplatelet drugs significantly affected decreases in the Hb level (regression coefficient [RC], 0.61; 95% confidence interval [CI], 0.14-1.08; P = 0.01). In addition to anticoagulant or antiplatelet drugs, multivariate analysis confirmed that the fracture type (Orthopedic Trauma Association classification A2: RC, 1.19; 95% CI, 0.71-1.67; P < 0.01; A3: RC, 2.47; 95% CI, 1.41-3.53; P < 0.01), platelet count (RC, -0.08; 95% CI, -0.12 to -0.04; P < 0.01), and operative time (RC, 0.02; 95% CI, 0.004-0.03; P = 0.01) affected the decreases in Hb level.The use of anticoagulants and antiplatelet agents is an independent risk factor for perioperative blood loss following proximal femoral fractures. Fracture type, platelet count, and operative time also affect perioperative blood loss. The fracture type was the greatest contributing factor to perioperative blood loss.Level of evidence grade: Prognostic level III.

  12. Behcet's disease without oral ulcers presenting with erythema nodosum and deep venous thrombosis.

    PubMed

    Ajmani, Sajal; Chowdhury, Abhra Chandra; Misra, Durga Prasanna; Agarwal, Vikas

    2016-01-01

    We present a young male with recurrent erythema nodosum and recent deep vein thrombosis with scrotal ulcers but no oral ulcers. He was diagnosed as having Behcet's disease (BD) and subsequently responded to immunosuppressants and anticoagulation. This case highlights that up to 2% patients with BD may not have oral ulcers. Timely institution of therapy in our patient resulted in a favorable outcome.

  13. Whose preferences should be elicited for use in health-care decision-making? A case study using anticoagulant therapy.

    PubMed

    Mott, David John; Najafzadeh, Mehdi

    2016-01-01

    The question of whose preferences to elicit in health-state valuation has been widely discussed in the literature. The importance of this debate lies in the fact that health-state utility values are used in health technology assessment (HTA); therefore, an individual's preferences can influence decision-making. If preferences differ across groups, making decisions based on one group's preferences may be suboptimal for the other. Preferences for benefits, risks, experiences and health states associated with anticoagulant therapies have been elicited by researchers due to the underutilization of warfarin and the introduction of non-vitamin K antagonist oral anticoagulants. The majority of existing studies elicit preferences from patient populations as opposed to other stakeholders such as the general public. This paper extends the preference debate by using this clinical area as a case study, with a particular focus on HTA guidelines and the recent advocacy of the use of preference information in benefit-risk assessments. PMID:26560704

  14. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  15. Synthetic oligosaccharides as heparin-mimetics displaying anticoagulant properties.

    PubMed

    Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J

    2003-01-01

    Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394

  16. Direct vitamin k antagonist anticoagulant treatment health care costs in patients with non-valvular atrial fibrillation

    PubMed Central

    2014-01-01

    Background There is evidence suggesting that most thromboembolic complications could be prevented with adequate pharmacological anticoagulation. We estimated the direct health care costs of anticoagulant treatment with oral vitamin K antagonists in patients diagnosed with non-valvular atrial fibrillation. Methods This observational study examined the clinical records of patients diagnosed with non-valvular atrial fibrillation who received anticoagulant treatment with oral vitamin K antagonists. Data from clinical records were used in the study: international normalized ratio, number of monitoring visits, type of anticoagulant, hospital admissions from complications, and concomitant medication. Drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the Diagnosis Related Group price for each case. Hospital visits costs were calculated by one of four different scenarios, using either the invoice rates for the regional health care authority or cost per visit as established by analytical accounting methods. Results We collected data from 1,257 patients diagnosed with non-valvular atrial fibrillation who were receiving oral anticoagulant therapy. Depending on the scheme used, the direct health care costs for these patients ranged from €423,695 - €1,436,038 per annum. The average cost per patient varied between €392 - €1,341, depending on the approach used. Patients with international normalized ratio values within the therapeutic range on 25% of their visits represented an average cost between €441.70 - €1,592. Those within the therapeutic range on 25%–50% of visits had associated costs of €512.37 - €1,703.91. When international normalized ratio values were within the therapeutic range on 50% - 75% of the visits, the costs ranged between €400.80- €1,375.74. The

  17. Citrate anticoagulation in the ICU: the Leeds experience.

    PubMed

    Trumper, Charlotte

    2016-09-01

    Continuous renal replacement therapy (CRRT) is widely used in the management of critically ill patients with acute kidney injury. It requires effective anticoagulation of the extracorporeal blood circuit. Although heparin is the most commonly prescribed anticoagulant, there are issues associated with heparin, and there has been increasing interest in regional citrate anticoagulation as an alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across the Trust. This article examines the reasons for the switch, the implementation of citrate and the impact of this quality-improvement project in terms of patient outcome data and feedback from the ICU nursing team. PMID:27615524

  18. Influence of Clinical Parameters and Anticoagulation on Intraprocedural Cerebral Microembolic Signals during Pulmonary Vein Isolation

    PubMed Central

    Leitz, Patrick; Guener, Fatih; Korsukewitz, Catharina; Dechering, Dirk; Pott, Christian; Wasmer, Kristina; Schmitges, Jan; Kerckhoff, Monika; Eckardt, Lars; Moennig, Gerold

    2016-01-01

    Objective We had the objective to determine the impact of clinical parameters and anticoagulation status on cerebral microembolic signals (MES) during pulmonary vein isolation (PVI) for atrial fibrillation (AF). Background Thromboembolism and stroke are the most feared complications of PVI. MES can help to evaluate embolic burden. It is unknown whether clinical parameters have an impact on embolic risk during PVI. Methods In this retrospective analysis we investigated the impact of clinical parameters, including the CHADS2- and CHA2DS2-VASc-score, pulmonary vein variants and echocardiographic parameters on MES rates in patients that underwent PVI using three different ablation approaches (radiofrequency ablation (iRF), pulmonary vein ablation catheter (PVAC) with deactivated electrode pair 1 or 5 (PVAC-red) or PVAC without deactivation (PVAC-all). Results 118 AF patients (61±12 years) were included between 2011 and 2013 (Median: 489 MES during PVI). Patients were more likely to have more MES (within 4th quartile) with the PVAC-all approach (60.7% vs. 25.0% (iRF) vs. 14.3% (PVAC-red) respectively (p<0.001). Patients with oral anticoagulation (OAC) pre-ablation were more likely to have lower MES-counts (1st-3rd quartile); (65.6% vs. 35.7%; p = 0.005). Additionally, patients with lower MES counts (1st-3rd quartile) had significantly higher INR values than those in the 4th quartile (1.78 vs. 1.09; p = 0.029). 2 patients developed a potentially thromboembolic event during the procedure. Conclusion Clinical predictors of cerebral emboli and stroke do not correlate with cerebral embolic burden during PVI. Pre-ablation OAC and increased INR values correlate with decreased MES-rates. Therefore, it might be beneficial to perform PVI with pre-ablation anticoagulation even in low risk patients. PMID:27327662

  19. Predicting outcomes among patients with atrial fibrillation and heart failure receiving anticoagulation with warfarin.

    PubMed

    Kim, Eun-Jeong; Ozonoff, Al; Hylek, Elaine M; Berlowitz, Dan R; Ash, Aelene S; Miller, Donald R; Zhao, Shibei; Reisman, Joel I; Jasuja, Guneet K; Rose, Adam J

    2015-07-01

    Among patients receiving oral anticoagulation for atrial fibrillation (AF), heart failure (HF) is associated with poor anticoagulation control. However, it is not known which patients with heart failure are at greatest risk of adverse outcomes. We evaluated 62,156 Veterans Health Administration (VA) patients receiving warfarin for AF between 10/1/06-9/30/08 using merged VA-Medicare dataset. We predicted time in therapeutic range (TTR) and rates of adverse events by categorising patients into those with 0, 1, 2, or 3+ of five putative markers of HF severity such as aspartate aminotransferase (AST)> 80 U/l, alkaline phosphatase> 150 U/l, serum sodium< 130 mEq/l, any receipt of metolazone, and any inpatient admission for HF exacerbation. These risk categories predicted TTR: patients without HF (referent) had a mean TTR of 65.0 %, while HF patients with 0, 1, 2, 3 or more markers had mean TTRs of 62.2 %, 57.2 %, 53.5 %, and 50.7 %, respectively (p< 0.001). These categories also discriminated for major haemorrhage well; compared to patients without HF, HF patients with increasing severity had hazard ratios of 1.84, 3.06, 3.52 and 5.14 respectively (p< 0.001). However, although patients with HF had an elevated hazard for bleeding compared to those without HF, these categories did not effectively discriminate risk of ischaemic stroke across HF. In conclusion, we developed a HF severity model using easily available clinical characteristics that performed well to risk-stratify patients with HF who are receiving anticoagulation for AF with regard to major haemorrhage. PMID:25948532

  20. Evaluation of intraoperative anticoagulants in microvascular free-flap surgery.

    PubMed Central

    Pugh, C. M.; Dennis, R. H.; Massac, E. A.

    1996-01-01

    This retrospective study evaluated anticoagulants used during surgery to determine efficacy and associated complications. The patient population was comprised of 15 patients who underwent microvascular free-flap surgery for wound coverage of the lower one third of the leg. Results indicated that the use of heparin in conjunction with other anticoagulants was associated with the development of more hematomas compared with the use of aspirin and dextran, both separately and together. PMID:8918071

  1. Anticoagulation with recombinant hirudin and danaparoid sodium in pediatric patients.

    PubMed

    Severin, Thomas; Zieger, Barbara; Sutor, Anton H

    2002-10-01

    Patients receiving heparin are at risk of developing heparin-induced thrombocytopenia (HIT). Whereas in HIT I only reversible mild thrombocytopenia occurs within the first days of heparin treatment, HIT II may lead to potentially life-threatening thromboembolic events. Pediatric patients suffering from HIT II have been reported in a study on newborns and in a few reports on children and adolescents. However, thrombotic complications can be as severe in children as they are in adults. In the case of HIT II, the withdrawal of heparin is required and alternative anticoagulation should be started. In contrast to numerous investigations in adult patients, including prospective studies, experience with alternative anticoagulants in pediatric patients is limited. The available data were analyzed according to HIT II complications, alternative anticoagulation, and clinical outcome. In conclusion, HIT II represents a potentially dangerous complication of heparin therapy in pediatric patients also. Alternative anticoagulation applied in pediatric patients mainly included danaparoid sodium and recombinant hirudin. In most patients treated with these anticoagulants, effective anticoagulation and clinical improvement were observed. Because of limited experience, more data are required for optimal management of HIT II in young patients. PMID:12420240

  2. Beyond heparin and warfarin: the new generation of anticoagulants.

    PubMed

    Weitz, Jeffrey I; Linkins, Lori-Ann

    2007-03-01

    Heparin and warfarin are widely used for the prevention and treatment of venous and arterial thromboembolism. Although effective, both agents have important limitations; for example, both drugs must be monitored, which is inconvenient for patients and for physicians. Heparin requires parenteral administration and can cause heparin-induced thrombocytopenia, an immune-mediated process that can lead to life-threatening thrombosis. Warfarin also has its limitations. Due to its slow onset of action, warfarin must be overlapped with heparin (or another rapidly acting anticoagulant) when treating patients with established thrombosis or who are at high risk for thrombosis. Warfarin dosing is variable because its activity is influenced by dietary intake of vitamin K, genetic polymorphisms in enzymes that are involved in its metabolism and numerous drug-drug interactions that promote or reduce its activity. New anticoagulants have been developed to overcome these problems. Building on a better understanding of coagulation pathways, advances in structure-based drug design and information derived from natural anticoagulants isolated from hematophagous organisms, most of the new anticoagulants target specific coagulation enzymes. Focussing on drugs that have at least completed Phase II evaluation, this article briefly reviews the coagulation pathways and its natural regulators; outlines the limitations of existing anticoagulants and identifies the opportunities for new ones; highlights the properties of selected new anticoagulants; describes the clinical trial results with these agents; and provides a perspective on their potential strengths and weaknesses. PMID:17302522

  3. Anticoagulation: where have we come from and where are we going? The evidence for and against novel anticoagulants.

    PubMed

    Symons, G

    2014-02-01

    Warfarin, one of the vitamin K antagonists, has been used since 1940, when it was first approved for the treatment of venous thromboembolism. It is currently the most commonly used anticoagulant, although alternative drugs are available, such as aspirin, clopidogrel and dipyridamol, which have been studied in a number of scenarios. The newest agents available to clinicians are the broad group of novel anticoagulants, such as direct thrombin and direct factor Xa inhibitors, including molecules such as dabigatran, rivaroxaban, apixaban and edoxaban.

  4. Do anticoagulation management services improve care? Implications of the Managing Anticoagulation Services Trial.

    PubMed

    Matchar, David B

    2003-12-01

    An Anticoagulation Clinic Service (ACS) has been proposed as one strategy for improving warfarin treatment for patients with atrial fibrillation. In the Managing Anticoagulation Services Trial (MAST), ACSs meeting specifications for high quality care were established in six managed care organizations (MCOs) which had the patients and resources to support this initiative. The trial followed 1165 patients age >or=65 years who had atrial fibrillation as the primary reason for anticoagulation and were enrolled in a participating MCO. The 593 patients in the intervention group saw physicians in a practice cluster which had randomly been assigned to have access to an ACS. These physicians used the ACS on average for about 48% of eligible patients. The 572 patients in the control group received care from physicians in a practice cluster which could not refer patients to the ACS established for the trial but was otherwise unrestricted. The two clusters were compared on the proportion of time warfarin-treated patients were in the target range (2-3) prothrombin time-international normalized ratio (INR) during a 9-month baseline and a 9-month follow-up period. Among patients ( n = 264) for whom data were available for both periods, the changes in percentages of time in the target range were similar in the intervention cluster (baseline: 47.7%; follow-up 55.6%) and in the control cluster (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5% to 14%; P = 0.32). In both practice clusters, patients had subtherapeutic INR values (1.5 to 1.99) about one fourth of the time. Providing an ACS in a managed care setting did not appear to improve anticoagulation care over the usual care provided at the sites in this trial but could be a reasonable consideration in a practice setting where time in target range is less than 50%. A higher rate of utilization and a more aggressive stance toward subtherapeutic INR values could potentially enhance the

  5. Laboratory measurement of the anticoagulant activity of edoxaban: a systematic review.

    PubMed

    Cuker, Adam; Husseinzadeh, Holleh

    2015-04-01

    Edoxaban, an oral direct inhibitor of factor Xa, was recently approved in the United States and Japan for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism (VTE). It is also licensed in Japan for prevention of VTE after major orthopedic surgery. Although routine laboratory monitoring of edoxaban is not required, laboratory measurement may be desirable in special circumstances. Our objective was to provide a systematic review of current evidence on laboratory measurement of the anticoagulant activity of edoxaban. PubMed and the Cochrane Library were searched for studies that reported a relationship between coagulation tests and plasma edoxaban levels. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We identified 9 eligible studies. Anti-Xa activity is linear across a broad range of drug levels (R (2) > 0.95) and may be used for edoxaban quantification. The assay shows greater variability at above on-therapy drug concentrations. The PT is less sensitive to edoxaban. A normal prothrombin time may not exclude clinically relevant on-therapy drug levels. The activated partial thromboplastin time has insufficient sensitivity to edoxaban for measurement of its anticoagulant activity. Edoxaban exhibits variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in edoxaban-treated patients. More data on the relationship between drug levels, coagulation test results, and clinical outcomes in patients are needed. PMID:25669624

  6. Optimizing adjunctive antithrombotic and anticoagulant therapy in primary PCI for STEMI.

    PubMed

    Deharo, Pierre; Rahbi, Hazim; Cuisset, Thomas

    2016-06-01

    The pharmacological management of patients with ST elevation myocardial infarction (STEMI) poses a significant challenge to the clinician. While mechanical reperfusion with primary percutaneous coronary intervention (PPCI) has proved its superiority over fibrinolysis, the best antithrombotic strategy surrounding the procedure remains a matter of debate. Due to the high risk of bleeding induced by antithrombotic drugs, the pharmacological management of STEMI needs to focus on an optimal strategy that reduces the rate of coronary thrombotic events without leading to excess bleeding. Intravenous anticoagulants are recommended for all patients presenting with STEMI. Low molecular heparin may be preferred over unfractionated heparin in the setting of PPCI. Recent data suggest that anticoagulation with bivalirudin can be utilized as an alternative strategy to heparin and Gp2b3a but this should be limited to patients at high risk of bleeding. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. New P2Y12 inhibitors (prasugrel and ticagrelor) have restricted clopidogrel use to situations where these potent agents are contraindicated. Whilst all oral antiplatelet agents have been used with an initial loading dose in STEMI, the time of their administration remains a controversial issue. In everyday practice, intravenous antiplatelet agents appear less consensual. While Gp2b3a receptor inhibitors use has been restricted to bailout situations, the place of cangrelor is not yet defined in real life daily practice.

  7. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS).

    PubMed

    Gebhart, Johanna; Posch, Florian; Koder, Silvia; Perkmann, Thomas; Quehenberger, Peter; Zoghlami, Claudia; Ay, Cihan; Pabinger, Ingrid

    2015-05-28

    Data on the clinical course of lupus anticoagulant (LA)-positive individuals with or without thrombotic manifestations or pregnancy complications are limited. To investigate mortality rates and factors that might influence mortality, we conducted a prospective observational study of LA-positive individuals. In total, 151 patients (82% female) were followed for a median of 8.2 years; 30 of the patients (20%) developed 32 thromboembolic events (15 arterial and 17 venous events) and 20 patients (13%) died. In univariable analysis, new onset of thrombosis (hazard ratio [HR] = 8.76; 95% confidence interval [CI], 3.46-22.16) was associated with adverse survival. Thrombosis remained a strong adverse prognostic factor after multivariable adjustment for age and hypertension (HR = 5.95; 95% CI, 2.43-14.95). Concomitant autoimmune diseases, anticoagulant treatment at baseline, or positivity for anticardiolipin- or anti-β2-glycoprotein I antibodies were not associated with mortality. In a relative survival analysis, our cohort of LA positives showed a persistently worse survival in comparison with an age-, sex-, and study-inclusion-year-matched Austrian reference population. The cumulative relative survival was 95.0% (95% CI, 88.5-98.8) after 5 years and 87.7% (95% CI, 76.3-95.6) after 10 years. We conclude that occurrence of a thrombotic event is associated with higher mortality in patients with LA. Consequently, the prevention of thromboembolic events in LA positives might improve survival.

  8. Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues

    PubMed Central

    Ryerson, Lindsay M.; Lequier, Laurence L.

    2016-01-01

    Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS. PMID:27446890

  9. Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues.

    PubMed

    Ryerson, Lindsay M; Lequier, Laurence L

    2016-01-01

    Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS. PMID:27446890

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

    PubMed

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

    2014-04-01

    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

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

    PubMed

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

    2014-04-01

    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.

  12. Detecting nonvalvular atrial fibrillation and anticoagulant therapy in cardioembolic ischemic stroke.

    PubMed

    Min, Jiangyong; Farooq, Muhammad Umar

    2016-08-01

    Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed. PMID:27263867

  13. Spontaneous iliopsoas muscle haematoma as a complication of anticoagulation in acute cerebral venous thrombosis: to stop or not to stop (the anticoagulation)?

    PubMed

    Fernandes, Carina; Pereira, Pedro; Rodrigues, Miguel

    2015-01-01

    Spontaneous iliopsoas muscle haematoma is an infrequent complication of anticoagulation, potentially causing neurological dysfunction through compression of the femoral nerve or lumbar plexus. The authors report the case of a puerperal woman admitted for an extensive cerebral venous thrombosis. Anticoagulation was started, with clinical improvement. The patient later reported low back pain irradiating to the right thigh and developed neurological impairment consistent with lumbar plexus dysfunction. A pelvic CT scan revealed a right iliopsoas muscle haematoma. Considering the risk of anticoagulation suspension, a conservative approach was chosen, with maintenance of anticoagulation. Clinical and functional improvement occurred, with mild right hip and knee flexion paresis as sequelae. Anticoagulation complications are challenging, especially when interruption of anticoagulation may threaten vital and functional outcomes. Therefore, a careful evaluation is essential, since no clinical guidelines are available. In this case, continuing anticoagulation provided a good functional outcome. PMID:25750219

  14. Anticoagulant and Fibrinolytic Disorders in Patients with Behçet's Disease and Recurrent Aphthous Ulcer.

    PubMed

    Shang, Hong; Ye, Jing-Jing; Ji, Min; Wang, Fu-Fang; Zhu, Yuan-Yuan; Qi, Xiang-Min

    2011-08-31

    Behçet's disease (BD) is a chronic multisystemic inflammatory disorder characterized by recurrent oral and genital aphthous ulcers, uveitis and skin lesions. Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in humans. The pathogenesis and thrombopoiesis of BD and RAU have not been fully clarified. To reveal the haemostatic dysfunctions in the patients with BD and RAU, we evaluated the levels of coagulant, anticoagulant and fibrinolytic parameters in these patients.Factor VIII clotting activity (FVIII:c), protein C antigen (PC:Ag), total protein S antigen (TPS: Ag), tissue-type plasminogen activator antigen (t-PA:Ag), plasminogen activator inhibitor-1 antigen (PAI-1:Ag) and D-dimer were detected in 24 BD, 58 RAU patients and 50 controls. Results showed that levels of PC:Ag, TPS:Ag, PAI-1:Ag and D-dimer were significantly elevated in both BD and RAU patients compared with controls (P<0.01). PAI-1:Ag was even higher in BD patients than in RAU patients (74.99±12.28 vs. 69.57±13.11, P<0.05), whereas the level of t-PA:Ag was significantly reduced in patients with BD and RAU (P<0.01). In patients with RAU, PC:Ag was lower in major aphthous ulcer (MjAU) group than in minor aphthous ulcer (MiAU) group (P<0.05). The expression of FVIII:c was significantly elevated in MiAU patients compared with controls (P<0.01), while no difference was observed between MjAU patients and controls (P>0.05). Our studies showed that there were anticoagulant and fibrinolytic disorders in BD patients, which may be responsible for diminished fibrinolysis in BD. Some haemostatic parameters may be correlated with the severity of RAU.

  15. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis

    PubMed Central

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-01

    Background Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. Material/Methods A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. Results The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Conclusions Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities. PMID:26790571

  16. A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy

    PubMed Central

    Bosch, Luis Ángel Bermúdez

    2014-01-01

    Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. PMID:25285240

  17. Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection

    PubMed Central

    Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P.; Ismail, Farooq

    2016-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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. PMID:27152278

  18. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics.

    PubMed

    Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P

    2015-01-01

    In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin) and anticoagulation (ie, warfarin) medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor) and anticoagulant (dabigatran) agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and anticoagulation therapy. However, several factors may limit its usefulness and should be considered. PMID:25897256

  19. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants.

    PubMed

    Broekema, Ferdinand I; van Minnen, Baucke; Jansma, Johan; Bos, Rudolf R M

    2014-03-01

    To avoid increasing the risk of thromboembolic events, it is recommended that treatment with anticoagulants should be continued during dentoalveolar operations. We have evaluated the incidence of bleeding after dentoalveolar operations in a prospective study of 206 patients, 103 who were, and 103 who were not, taking anticoagulants. Seventy-one were taking thrombocyte aggregation inhibitors and 32 vitamin K antagonists. Patients were treated according to guidelines developed at the Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. The operations studied included surgical extraction (when the surgeon had to incise the gingiva before extraction), non-surgical extraction, apicectomy, and placement of implants. Patients were given standard postoperative care and those taking vitamin K antagonists used tranexamic acid mouthwash postoperatively. No patient developed a severe bleed that required intervention. Seven patients (7%) taking anticoagulants developed mild postoperative bleeds. Patients taking vitamin K antagonists reported 3 episodes (9%) compared with 4 (6%) in the group taking thrombocyte aggregation inhibitors. Among patients not taking anticoagulants, two (2%) developed mild bleeding. The differences between the groups were not significant. All bleeding was controlled by the patients themselves with compression with gauze. We conclude that dentoalveolar surgery is safe in patients being treated with anticoagulants provided that the conditions described in the ACTA guidelines are met. PMID:24485810

  20. Marine sulfated glycans with serpin-unrelated anticoagulant properties.

    PubMed

    Glauser, Bianca F; Mourão, Paulo A S; Pomin, Vitor H

    2013-01-01

    Marine organisms are a rich source of sulfated polysaccharides with unique structures. Fucosylated chondroitin sulfate (FucCS) from the sea cucumber Ludwigothurea grisea and sulfated galactan from the red alga Botryocladia occidentalis are one of these unusual molecules. Besides their uncommon structures, they also exhibit high anticoagulant and antithrombotic effects. Earlier, it was considered that the anticoagulant activities of these two marine glycans were driven mainly by a catalytic serpin-dependent mechanism likewise the mammalian heparins. Its serpin-dependent anticoagulant action relies on promoting thrombin and/or factor Xa inhibition by their specific natural inhibitors (the serpins antithrombin and heparin cofactor II). However, as opposed to heparins, these two previously mentioned marine glycans were proved still capable in promoting coagulation inhibition using serpin-free plasmas. This puzzle observation was further investigated and clearly demonstrated that the cucumber FucCS and the red algal sulfated galactan have an unusual serpin-independent anticoagulant effect by inhibiting the formation of factor Xa and/or thrombin through the procoagulants tenase and prothrombinase complexes, respectively. These marine polysaccharides with unusual anticoagulant effects open clearly new perspectives for the development of new antithrombotic drugs as well as push the glycomics project.

  1. Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy.

    PubMed

    Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele

    2016-06-30

    This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice. PMID:27393877

  2. Limited evidence on persistence with anticoagulants, and its effect on the risk of recurrence of venous thromboembolism: a systematic review of observational studies

    PubMed Central

    Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar

    2016-01-01

    Purpose The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. Methods PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach. Results In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%), 62% (95% CI, 58–66; I2=98.1%), and 31% (95% CI, 22–40; I2=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months. Conclusion Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE

  3. Limited evidence on persistence with anticoagulants, and its effect on the risk of recurrence of venous thromboembolism: a systematic review of observational studies

    PubMed Central

    Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar

    2016-01-01

    Purpose The risk of venous thromboembolism (VTE) recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients. Methods PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach. Results In total, 12 observational studies (7/12 conference abstracts) were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%), 62% (95% CI, 58–66; I2=98.1%), and 31% (95% CI, 22–40; I2=99.8%), respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months. Conclusion Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months. Observational data on persistence with anticoagulation treatment, especially direct oral anticoagulants, in patients with VTE and its effect on risk of VTE

  4. [Heparin induced thrombocytopenia and anticoagulation in renal replacemant therapy].

    PubMed

    Steinfeldt, Thorsten; Rolfes, Caroline

    2008-04-01

    The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

  5. Thrombotic and hemorrhagic complications in children with the lupus anticoagulant.

    PubMed

    Bernstein, M L; Salusinsky-Sternbach, M; Bellefleur, M; Esseltine, D W

    1984-12-01

    Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two. PMID:6439032

  6. Gold nanoparticles in the engineering of antibacterial and anticoagulant surfaces.

    PubMed

    Ehmann, Heike M A; Breitwieser, Doris; Winter, Sascha; Gspan, Christian; Koraimann, Günther; Maver, Uros; Sega, Marija; Köstler, Stefan; Stana-Kleinschek, Karin; Spirk, Stefan; Ribitsch, Volker

    2015-03-01

    Simultaneous antibacterial and anticoagulant surfaces have been prepared by immobilization of engineered gold nanoparticles onto different kinds of surfaces. The gold nanoparticle core is surrounded by a hemocompatible, anticoagulant polysaccharide, 6-O chitosan sulfate, which serves as reduction and stabilizing agent for the generation of gold nanoparticles in a microwave mediated reaction. The particle suspension shows anticoagulant activity, which is investigated by aPTT and PT testing on citrated blood samples of three patients suffering from congenital or acquired bleeding disorders. The amount of nanoparticles deposited on the surfaces is quantified by a quartz crystal microbalance with dissipation unit. All gold containing surfaces exhibit excellent antimicrobial properties against the chosen model organism, Escherichia coli MG 1655 [R1-16]. Moreover, blood plasma coagulation times of the surfaces are increased after deposition of the engineered nanoparticles as demonstrated by QCM-D.

  7. Efficiency of three anti-coagulant rodenticides on commensal rodents.

    PubMed

    Mikhail, M W; Kamilia; Allam, A M; Soliman, M I

    2007-08-01

    Susceptibiliy level to bromadilone, difencoum and coumtertraly anticoagulants were studied in different species of Norway rat Rattus norvegicus and roof rat Rattus rattus trapped from El-Qualyobia Governorate in which the anticoagulant rodenticides were used to control rodents for long periods in some rural regions at Qualyobia. Complete mortality was showed for both species and sex within a standard feeding period (6 days) indicated to be susceptible to the three anticoagulant rodenticides. The bait eaten and corresponding active ingredient showed a noticeable more intake for R. rattus than R. norvegicus for the three compounds. The time to death showed highest mean values for R. rattus comparison to R. norvegicus. Difencoum recorded highest values of time to death compare with bromadilone and coumatetralyl. PMID:17926811

  8. [Intramural hematoma of the ileum complicating anticoagulant therapy].

    PubMed

    Acea Nebril, B; Sánchez González, F; Aguirrezabalaga González, J; Crespo García, C; Lago Novoa, M; Blanco Freire, N

    1994-07-01

    The development of abdominal pain in the patient receiving anticoagulant therapy is more likely to pose a diagnostic dilemma. A group of intra-abdominal bleeding syndromes, which are extremely rare in patients with normal haemostasis, have been described in patients on anticoagulant therapy. Theses syndromes are of particular interest to surgeons because they simulate acute surgical conditions of the abdomen. We herein report the preoperative diagnosis of a spontaneous intramural hematoma of the small bowel by computed tomography. The authors conclude that CT should be used early in the diagnostic evaluation of abdominal pain and of acute abdomen in patients receiving anticoagulant therapy. Indications for the operative management of these patients include active bleeding, pneumoperitoneum, failure to improve with conservative management within 72 hours, worsening of symptoms, and uncertain diagnosis.

  9. The use of anticoagulation in pediatric cardiac disease

    PubMed Central

    Boris, JR; Harris, MA

    2003-01-01

    Palliation and repair of increasingly complex congenital heart defects as well as the emergence of novel contexts has led to multiple scenarios in which a real or potential risk of thromboembolism may exist. While various anticoagulation methodologies have been well defined for adults, there are few studies relating directly to pediatric patients. This article reviews a number of specific pediatric disease states, the representative pediatric literature, and, where appropriate, the corresponding adult literature. In so doing, the art and science of pediatric cardiac anticoagulation is defined with the hope to engender further thought regarding future directions of study and therapy. PMID:22368628

  10. 21st century twist on Cullen's sign: new generation anticoagulants and splenic traum.

    PubMed

    Bilkhu, Amarvir; Mosley, Frances; Gokhale, Jay A

    2016-01-01

    New anticoagulants such as Rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism, chiefly because anticoagulation is maintained without the need for monitoring. This can be problematic in cases of trauma, and in this article, we discuss the management and outcome of managing an elderly patient with a shattered spleen while on Rivaroxaban. PMID:27511911

  11. 21st century twist on Cullen's sign: new generation anticoagulants and splenic traum

    PubMed Central

    Bilkhu, Amarvir; Mosley, Frances; Gokhale, Jay A.

    2016-01-01

    New anticoagulants such as Rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism, chiefly because anticoagulation is maintained without the need for monitoring. This can be problematic in cases of trauma, and in this article, we discuss the management and outcome of managing an elderly patient with a shattered spleen while on Rivaroxaban. PMID:27511911

  12. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology. PMID:16277953

  13. [Oral ulcers].

    PubMed

    Bascones-Martínez, Antonio; Figuero-Ruiz, Elena; Esparza-Gómez, Germán Carlos

    2005-10-29

    Ulcers commonly occur in the oral cavity, their main symptom being pain. There are different ways to classify oral ulcers. The most widely accepted form divides them into acute ulcers--sudden onset and short lasting--and chronic ulcers--insidious onset and long lasting. Commonest acute oral ulcers include traumatic ulcer, recurrent aphthous stomatitis, viral and bacterial infections and necrotizing sialometaplasia. On the other hand, oral lichen planus, oral cancer, benign mucous membrane pemphigoid, pemphigus and drug-induced ulcers belong to the group of chronic oral ulcers. It is very important to make a proper differential diagnosis in order to establish the appropriate treatment for each pathology.

  14. Identification of potent orally active factor Xa inhibitors based on conjugation strategy and application of predictable fragment recommender system.

    PubMed

    Ishihara, Tsukasa; Koga, Yuji; Iwatsuki, Yoshiyuki; Hirayama, Fukushi

    2015-01-15

    Anticoagulant agents have emerged as a promising class of therapeutic drugs for the treatment and prevention of arterial and venous thrombosis. We investigated a series of novel orally active factor Xa inhibitors designed using our previously reported conjugation strategy to boost oral anticoagulant effect. Structural optimization of anthranilamide derivative 3 as a lead compound with installation of phenolic hydroxyl group and extensive exploration of the P1 binding element led to the identification of 5-chloro-N-(5-chloro-2-pyridyl)-3-hydroxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzamide (33, AS1468240) as a potent factor Xa inhibitor with significant oral anticoagulant activity. We also reported a newly developed Free-Wilson-like fragment recommender system based on the integration of R-group decomposition with collaborative filtering for the structural optimization process.

  15. Oral cancer

    MedlinePlus

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... Oral cancer most commonly involves the lips or the tongue. It may also occur on the: Cheek lining Floor ...

  16. Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity

    PubMed Central

    Lei, Liang; Xue, Yong-bo; Liu, Zhong; Peng, Si-si; He, Yan; Zhang, Yang; Fang, Rong; Wang, Jian-ping; Luo, Zeng-wei; Yao, Guang-min; Zhang, Jin-wen; Zhang, Geng; Song, Hong-ping; Zhang, Yong-hui

    2015-01-01

    Coumarin derivatives are an important class of C6–C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4–8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting. PMID:26315062

  17. Shock wave lithotripsy in patients requiring anticoagulation or antiplatelet agents.

    PubMed

    Alsaikhan, Bader; Andonian, Sero

    2011-02-01

    Extracorporeal shockwave lithotripsy (SWL) remains the only truly minimally invasive procedure for the treatment of upper tract nephrolithiasis. Recently, there has been a recent rise in the patients on antiplatelet agents. Therefore, the aim of the present study is to review the literature available regarding SWL in these high-risk patients requiring anti-coagulation therapy. Alternative therapies to SWL are also presented.

  18. Anticoagulant activity of some Artemisia dracunculus leaf extracts

    PubMed Central

    Duric, Kemal; Kovac-Besovic, Elvira E.; Niksic, Haris; Muratovic, Samija; Sofic, Emin

    2015-01-01

    Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%. The INR value of normal plasma in testing this extract was 1.05. PMID:26042507

  19. Can the anticoagulant effects of dabigatran be reversed?

    PubMed

    Bickley, Aida Rebecca; Wallace, Caleb

    2016-09-01

    Idarucizumab is a humanized monoclonal antibody fragment for reversal of the anticoagulant effects of dabigatran. This drug can be used for patients who need emergency surgery or invasive procedures, as well as those with life-threatening or uncontrolled bleeding. PMID:27575900

  20. Qualitative identification of rodenticide anticoagulants by LC-MS/MS.

    PubMed

    Middleberg, Robert A; Homan, Joseph

    2012-01-01

    Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. Before the advent of LC-MS/MS, analysis for such agents was relegated to such techniques as TLC and HPLC with nonspecific modes of detection. LC-MS/MS has been used to determine any given number of rodenticide anticoagulants in animal tissues, foods, plasma, etc. Use of this technique allows for the simultaneous identification of individual compounds within both classes of rodenticide anticoagulants. The LC-MS/MS method presented allows for simultaneous qualitative identification of brodifacoum, bromadiolone, chlorphacinone, dicumarol, difenacoum, diphacinone, and warfarin in blood, serum, and plasma using ESI in the negative mode. Two transitions are monitored for each analyte after a simple sample preparation. Chromatographic separation is accomplished using a gradient of ammonium hydroxide in water and ammonium hydroxide in methanol. Chloro-warfarin is used as internal standard. PMID:22767114

  1. Contact laser prostatectomy in a patient on chronic anticoagulation

    NASA Astrophysics Data System (ADS)

    Mueller, Edward J.

    1995-05-01

    The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

  2. Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial

    PubMed Central

    Bentley, D P; Prescott, R J; Routledge, P A; Shetty, H G M; Williamson, I J

    2007-01-01

    Objective To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both. Design Multicentre, prospective, randomised study with follow-up for one year. Setting 46 hospitals in United Kingdom. Participants Patients aged ≥18 with deep vein thrombosis or pulmonary embolism, or both. Interventions Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0-3.5. Main outcome measures Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment. Results In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non-fatal recurrences in the three month group and 16 in the six month group. Fatal and non-fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference −3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for six months and none in those treated for three months (P=0.008, −3.5% to −0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0

  3. Is anticoagulation required in plasmapheresis? A University Hospital Experience in Bogota, Colombia.

    PubMed

    Córdoba, Juan Pablo; Larrarte, Carolina; Ruiz, Alvaro

    2013-06-01

    Anticoagulation has been considered essential during plasmapheresis. International publications and guidelines state that anticoagulation should be administered during therapy to avoid circuit clotting and impaired effectiveness. However, anticoagulation has also been associated with bleeding, fluid and electrolyte imbalances and hematological alterations. No published studies have looked at the risk to benefit ratio of the common practice of circuit anticoagulation. We describe the experience with 367 plasmapheresis sessions, in the Hospital Universitario San Ignacio, a tertiary care center in Bogota, Colombia, where no anticoagulation is used in any case. Patient characteristics and therapy complications are described. Coagulation of circuit was never reported.

  4. Relationship between anticoagulant activities and polyanionic properties of rabbit thrombomodulin.

    PubMed

    Bourin, M C; Ohlin, A K; Lane, D A; Stenflo, J; Lindahl, U

    1988-06-15

    Rabbit thrombomodulin displays three distinct blood anticoagulant activities: it promotes the activation of protein C by thrombin (protein C activation cofactor activity); it promotes the inactivation of thrombin by thrombin (direct anticoagulant activity). The effects on these activities of mouse anti-thrombomodulin monoclonal antibodies and of the heparin-neutralizing proteins, platelet factor 4, histidine-rich glycoprotein, and S-protein, were investigated. One of the antibodies, which did not influence the functional properties of thrombomodulin, was used as an immunoaffinity ligand for purification of the protein. Two other antibodies, which were found to abrogate the protein C activation cofactor activity of the purified thrombomodulin, also abolished the antithrombin-dependent and the direct anticoagulant activities. The heparin-neutralizing proteins all inhibited the two latter activities, albeit to a varying extent, but did not appreciably affect the activation of protein C. These results are interpreted in relation to our previous finding that rabbit thrombomodulin contains an acidic domain, tentatively identified as a sulfated glycosaminoglycan (Bourin, M.-C., Boffa, M.-C., Björk, I., and Lindahl, U. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5924-5928). It is proposed that the acidic domain interacts with thrombin at the protein C activation site and that this interaction is a prerequisite to the expression of direct as well as antithrombin-dependent anticoagulant activity. The interaction is not essential to, but compatible with, the activation of protein C. Experiments involving treatment of thrombomodulin with various glycanases or with nitrous acid, followed by measurement of anticoagulant activities, indicated that the acidic domain is constituted by a sulfated galactosaminoglycan and not by a heparin-related polysaccharide as previously suggested.

  5. Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate.

    PubMed

    Glauser, Bianca F; Pereira, Mariana S; Monteiro, Robson Q; Mourão, Paulo A S

    2008-09-01

    Fucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber composed of a chondroitin sulfate-like core with branches of sulfated fucose. This glycosaminoglycan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant activity is mostly due to activating thrombin inhibition by heparin cofactor II. Here, we evaluated the anticoagulant activity of fucosylated chondroitin sulfate using antithrombin- and heparin cofactor II-free plasmas. In contrast to mammalian heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas. These observations suggest that fucosylated chondroitin sulfate has a serpin-independent anticoagulant effect. We further investigated this effect using purified blood coagulation proteins. Clearly, fucosylated chondroitin sulfate inhibits the intrinsic tenase and prothrombinase complexes, which are critical for thrombin generation. It is possible that the invertebrate chondroitin sulfate inhibits interactions between cofactor Va and factor Xa. We also employed chemically modified polysaccharides in order to trace a structure versus activity relationship. Removal of the sulfated fucose branches, but not reduction of the glucuronic acid residues to glucose, abolished its activity. In conclusion, fucosylated chondroitin sulfate has broader effects on the coagulation system than mammalian glycosaminoglycans. In addition to its serpin-dependent inhibition of coagulation protease, it also inhibits the generation of factor Xa and thrombin by the tenase and prothrombinase complexes, respectively. In plasma systems, the serpin-independent anticoagulant effect of fucosylated chondroitin sulfate predominates over its serpin-dependent action. This glycosaminoglycan opens new avenues for the development of antithrombotic agents.

  6. A method for anticoagulation of children on mechanical circulatory support.

    PubMed

    Copeland, Hannah; Nolan, Paul E; Covington, Diane; Gustafson, Monica; Smith, Richard; Copeland, Jack G

    2011-11-01

    Anticoagulation of children on mechanical circulatory support presents a challenge. We implanted 28 devices in children and infants using a consistent anticoagulation protocol. We performed a retrospective review of all children implanted in our program with mechanical assist devices since 1997. Heparin, dipyridamole, and aspirin were used for anticoagulation and antiaggregation. Coagulation monitoring included thromboelastography (TEG), platelet aggregration studies, international normalized ratio, partial thromboplastin time, and platelet count. Twenty-eight children, ages 1 month to 16 years (mean 5.3; median 2.4 years), were implanted for 3-107 days (mean 27; median 17). Eighteen received left ventricular assist devices, seven received biventricular assist devices, and three received total artificial hearts. Adverse events during the 720 days of device support included the following: six (21%) reoperations for bleeding; seven strokes (25%): two fatal, two with a mild residual deficit, and three without deficit; and three (11%) visceral emboli: two fatal and one nonfatal. There were eight deaths (29%). Causes of death were embolic (four), graft failure post-transplantation (one), preimplant anoxic brain damage (two), and postexplant heart failure (one). 24/28 (86%) survived to transplantation or weaning from device and 20/28 (71%) were discharged from the hospital, 10 after transplantation and 10 after native heart recovery. All 20 early survivors survived long term. We describe an anticoagulation protocol based upon TEG and platelet aggregation studies and using heparin, aspirin, and dipyridamole. Adequate anticoagulation is more difficult in children. However, 71% of the patients in our study survived long term.

  7. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab.

    PubMed

    Honickel, Markus; Treutler, Stefanie; van Ryn, Joanne; Tillmann, Sabine; Rossaint, Rolf; Grottke, Oliver

    2015-04-01

    Urgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.

  8. Cognitive function and adherence to anticoagulation treatment in patients with atrial fibrillation

    PubMed Central

    Jankowska-Polańska, Beata; Katarzyna, Lomper; Lidia, Alberska; Joanna, Jaroch; Dudek, Krzysztof; Izabella, Uchmanowicz

    2016-01-01

    Background Medication adherence is an integral part of the comprehensive care of patients with atrial fibrillation (AF) receiving oral anticoagulations (OACs) therapy. Many patients with AF are elderly and may suffer from some form of cognitive impairment. This study was conducted to investigate whether cognitive impairment affects the level of adherence to anticoagulation treatment in AF patients. Methods The study involved 111 AF patients (mean age, 73.5 ± 8.3 years) treated with OACs. Cognitive function was assessed using the Mini Mental State Examination (MMSE). The level of adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8). Scores on the MMAS-8 range from 0 to 8, with scores < 6 reflecting low adherence, 6 to < 8 medium adherence, and 8 high adherence. Results 46.9% of AF patients had low adherence, 18.8% had moderate adherence, and 33.3% had high adherence to OACs. Patients with lower adherence were older than those with moderate or high adherence (76.6 ± 8.7 vs. 71.3 ± 6.4 vs. 71.1 ± 6.7 years) and obtained low MMSE scores, indicating cognitive disorders or dementia (MMSE = 22.3 ± 4.2). Patients with moderate or high adherence obtained high MMSE test results (27.5 ± 1.7 and 27.5 ± 3.6). According to Spearman's rank correlation, worse adherence to treatment with OACs was determined by older age (rS = −0.372) and lower MMSE scores (rS = 0.717). According to multivariate regression analysis, the level of cognitive function was a significant independent predictor of adherence (b = 1.139). Conclusions Cognitive impairment is an independent determinant of compliance with pharmacological therapy in elderly patients with AF. Lower adherence, beyond the assessment of cognitive function, is related to the age of patients. PMID:27605935

  9. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  10. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  11. 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.

  12. Is Anticoagulation Discontinuation Achievable with Citrate Dialysate during HDF Sessions?

    PubMed Central

    Oger, Emmanuel; Hamel, Didier; Lombart, Marie-Laure; Hermès, Isabelle

    2016-01-01

    Citrate dialysate has been developed for few years to replace acetate and HCl concentrates. In Online Postdilution Hemodiafiltration (OL-POST-HDF), several issues are remaining concerning the possibility of stopping anticoagulation during sessions and the side effects of citrate solutions on calcium metabolism. This 1-year monocentric retrospective study included all patients exposed to citrate in OL-POST-HDF with nadroparin decrease for more than one month. Clotting events, serum calcium, PTH, hemoglobin, CRP, depuration parameters, and treatments administrated were recorded for analysis. 27 patients experienced nadroparin decrease and 5 did not receive nadroparin at the end of the study. Nadroparin decrease and withdrawal were both associated with more clotting events whereas the use of vitamin K antagonists was protective. No significant metabolic side effects were observed. Citrate dialysate does not allow anticoagulation discontinuation or decrease but has no significant side effects on mineral bone metabolism or erythropoiesis. PMID:27803814

  13. The enhanced anticoagulation for graphene induced by COOH(+) ion implantation.

    PubMed

    Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun

    2015-01-01

    Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene) interacting with red blood cells and platelets. In this paper, COOH(+)/graphene was prepared by modified Hummers' method and implanted by COOH(+) ions. The structure and surface chemical and physical properties of COOH(+)/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH(+)/graphene has significant anticoagulation. In addition, at the dose of 5 × 10(17) ions/cm(2), COOH(+)/graphene responded best on platelet adhesion, aggregation, and platelet activation.

  14. Coagulant and anticoagulant activities in Jatropha curcas latex.

    PubMed

    Osoniyi, Omolaja; Onajobi, Funmi

    2003-11-01

    Jatropha curcas Linn. (Euphorbiaceae), a medicinal plant commonly grown in the Tropics, is traditionally used as a haemostatic. Investigation of the coagulant activity of the latex of Jatropha curcas showed that whole latex significantly (P<0.01) reduced the clotting time of human blood. Diluted latex, however, prolonged the clotting time: at high dilutions, the blood did not clot at all. This indicates that Jatropha curcas latex possesses both procoagulant and anticoagulant activities. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests on plasma confirm these observations. Solvent partitioning of the latex with ethyl acetate and butanol led to a partial separation of the two opposing activities: at low concentrations, the ethyl acetate fraction exhibited a procoagulant activity, while the butanol fraction had the highest anticoagulant activity. The residual aqueous fraction had no significant effect on the clotting time of blood and the PT but slightly prolonged the APTT.

  15. [Anticoagulant activity of coumarins from Ferula communis L].

    PubMed

    Lamnaouer, D

    1999-01-01

    Ferula communis is an ombelliferous plant of the Mediterranean regions. It is represented in Morocco by two varieties: brevifolia and genuina. The later is very rich in a soap or resinous gum. This product, collected from the roots, is largely used in traditional medicine. It is know as fessoukh in Morocco and other Arab countries. This plant is also well known for its toxicity and its anticoagulant activity. In the present review, are discussed: (1) the ethnobotany of the plant, especially medicinal uses of fessoukh in traditional medicine as well as alimentary use of young stems as legumes; (2) clinical and biochemical data of intoxication by this plant, which are dominated by haemorrhage as a consequence of blood coagulation disturbance; (3) 4-hydroxycoumarins isolated from Ferula communis L. and their anticoagulant activity; (4) the role of vitamin K1 in the treatment of poisoning by this plant.

  16. [Bilateral renal infarction after discontinuation of anticoagulant therapy].

    PubMed

    Lavoignet, Charles-Éric; Le Borgne, Pierrick; Ugé, Sarah; Veneziano, Rinaldo; Brunhuber, Claudia; Kam, Claire; Bilbault, Pascal

    2016-07-01

    Acute renal infarction is an uncommon and often under diagnosed condition mostly because of misleading symptoms. Accurate data regarding clinical presentation, laboratory tests, diagnostic and treatment are lacking. Detection is often delayed or missed because of non-specific clinical presentation. The mechanisms of acute renal infarction are various, mainly embolic or thrombotic. Abdominal CT scan remains the most valuable exam to confirm the diagnosis. Therapeutic guidelines for the treatment of renal embolism have not been well established. The standard treatment strategy includes anticoagulation with or without thrombolysis. Despite the uncertainty regarding management, the renal outcome remains favorable. Some patients do develop some degree of renal insufficiency during the acute episode. We report here the case of a 73-year-old woman with bilateral acute renal infarction after discontinuation of anticoagulant therapy.

  17. New anticoagulant and antiplatelet agents: a primer for the gastroenterologist.

    PubMed

    Baron, Todd H; Kamath, Patrick S; McBane, Robert D

    2014-02-01

    A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed. PMID:23735447

  18. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management

    PubMed Central

    Shamoun, Fadi; Obeid, Hiba; Ramakrishna, Harish

    2015-01-01

    Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. PMID:26221593

  19. Evaluation of anticoagulant activity of two algal polysaccharides.

    PubMed

    Faggio, C; Pagano, M; Dottore, A; Genovese, G; Morabito, M

    2016-09-01

    Marine algae are important sources of phycocolloids like agar, carrageenans and alginates used in industrial applications. Algal polysaccharides have emerged as an important class of bioactive products showing interesting properties. The aim of our study was to evaluate the potential uses as anticoagulant drugs of algal sulphate polysaccharides extracted from Ulva fasciata (Chlorophyta) and Agardhiella subulata (Rhodophyta) collected in Ganzirri Lake (Cape Peloro Lagoon, north-eastern Sicily, Italy). Toxicity of algal extracts through trypan blue test and anticoagulant action measured by activated partial thromboplastin time (APTT), prothrombin time (PT) test has been evaluated. Algal extracts showed to prolong the PT and APTT during the coagulation cascade and to avoid the blood coagulation of samples. Furthermore, the algal extracts lack toxic effects towards cellular metabolism and their productions are relatively at low cost. This permits to consider the algae as the biological source of the future.

  20. Effect of citrate anticoagulants on factor VIII levels in plasma.

    PubMed

    Rock, G; Tittley, P; Fuller, V

    1988-01-01

    The citrate anticoagulants used during blood collection have been developed for their benefits to red cells. The concentrations in which they are used are strictly regulated in the United States: citrate-phosphate-dextrose-adenine (CPDA) is used in a 1:8 ratio for the collection of whole blood, whereas 4 percent sodium citrate (NaCit) is used in a 1:10 ratio for manual plasmapheresis. Acid-citrate-dextrose formula A (ACD-A) or formula B (ACD-B) and NaCit are commonly used in a 1:12 or 1:15 ratio during automated plasmapheresis. These anticoagulants have different initial and final pH values and citrate concentrations and different effects on the recovery of factor VIII (FVIII) in the plasma. NaCit has a higher initial pH (6.64) than ACD-A (4.98), ACD-B (5.60), or CPDA (5.12). The effects of these different anticoagulants on plasma constituents obtained from six healthy subjects were studied. In standard citrate concentrations, the FVIII level was significantly lower (p less than 0.05) in the NaCit used for manual plasmapheresis than in either of the ACD solutions used in automated plasmapheresis (104 U/dl vs. 153 and 160 U/dl). When various ratios of NaCit to blood were used, the pH increased from 7.62 at a 1:10 dilution to 7.65 at a 1:50 dilution. As expected, a progressive decrease in anticoagulant level was associated with an increase in ionized calcium and also in the level of FVIII, with the latter values rising from 104 U per dl at 1:10 to 137 at 1:20 and 148 U per dl at 1:30. Clot formation was detected only at a ratio of 1:35.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The Genetic Basis of Resistance to Anticoagulants in Rodents

    PubMed Central

    Pelz, Hans-Joachim; Rost, Simone; Hünerberg, Mirja; Fregin, Andreas; Heiberg, Ann-Charlotte; Baert, Kristof; MacNicoll, Alan D.; Prescott, Colin V.; Walker, Anne-Sophie; Oldenburg, Johannes; Müller, Clemens R.

    2005-01-01

    Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents. PMID:15879509

  2. The genetic basis of resistance to anticoagulants in rodents.

    PubMed

    Pelz, Hans-Joachim; Rost, Simone; Hünerberg, Mirja; Fregin, Andreas; Heiberg, Ann-Charlotte; Baert, Kristof; MacNicoll, Alan D; Prescott, Colin V; Walker, Anne-Sophie; Oldenburg, Johannes; Müller, Clemens R

    2005-08-01

    Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents. PMID:15879509

  3. Anticoagulation in chronic kidney disease patients—the practical aspects

    PubMed Central

    Hughes, Stephen; Szeki, Iren; Nash, Michael J.; Thachil, Jecko

    2014-01-01

    There is an increasing awareness about the risks of arterial and venous thromboembolism (TE) in hospital patients and general public which has led to consideration of thrombosis prevention measures in earnest. Early recognition of the symptoms of TE disease has led to timely administration of antiplatelet and anticoagulant drugs, translating to better outcome in many of these patients. In this respect, patients with chronic kidney disease (CKD) represent a special group. They indeed represent a high-risk group for thrombosis both in the cardiovascular territory and also in the venous circulation. At the same time, abnormalities in the platelet membranes put them at risk of bleeding which is significantly more than other patients with chronic diseases. Anticoagulation may be ideal to prevent the former, but the co-existing bleeding risk and also that the commonly used drugs for inhibiting coagulation are eliminated by renal pathways pose additional problems. In this review, we try to explain the complex thrombotic-haemorrhagic state of chronic kidney disease patients, and practical considerations for the management of anticoagulation in them with a focus on heparins. PMID:25878775

  4. Endovascular Embolization of Spontaneous Retroperitoneal Hemorrhage Secondary to Anticoagulant Treatment

    SciTech Connect

    Isokangas, Juha-Matti Peraelae, Jukka M.

    2004-11-15

    The purpose of this study was to report a single hospital's experience of endovascular treatment of patients with retroperitoneal hemorrhage (RPH) secondary to anticoagulant treatment. Ten consecutive patients treated in an intensive care unit and needing blood transfusions due to RPH secondary to anticoagulation were referred for digital subtraction angiography (DSA) to detect the bleeding site(s) and to evaluate the possibilities of treating them by transcatheter embolization. DSA revealed bleeding site(s) in all 10 patients: 1 lumbar artery in 4 patients, 1 branch of internal iliac artery in 3 patients and multiple bleeding sites in 3 patients. Embolization could be performed in 9 of them. Coils, gelatin and/or polyvinyl alcohol were used as embolic agents. Bleeding stopped or markedly decreased after embolization in 8 of the 9 (89%) patients. Four patients were operated on prior to embolization, but surgery failed to control the bleeding in any of these cases. Abdominal compartment syndrome requiring surgical or radiological intervention after embolization developed in 5 patients. One patient died, and 2 had sequelae due to RPH. All 7 patients whose bleeding stopped after embolization had a good clinical outcome. Embolization seems to be an effective and safe method to control the bleeding in patients with RPH secondary to anticoagulant treatment when conservative treatment is insufficient.

  5. Popular naturally occurring antioxidants as potential anticoagulant drugs.

    PubMed

    Bijak, Michal; Saluk, Joanna; Szelenberger, Rafal; Nowak, Pawel

    2016-09-25

    Blood coagulation is a physiological process whose main task is prevention of blood loss from injured vessels. This process consists of a series of zymogens proteolytic activation leading to the generation of the main coagulation enzyme - thrombin. Besides its important role in blood coagulation process, thrombin is involved in many cardiovascular diseases, which are responsible for almost half of fatalities in economically developed countries. The evidence for the increased generation and in vivo activity of thrombin was observed in the plasma of individuals at high risk for clinically significant venous and arterial thromboembolic complications. Antioxidants activity of plants extracts has been well known for many years and was confirmed by many publications. However, during the last decade many research centers presented results suggesting anticoagulant potential of various plant extracts. Many researchers have also provided evidence that polyphenol compounds are able to inhibit the activity of many enzymes, including serine proteases. All research described in this review clearly indicate that polyphenols and polyphenol-rich extracts possess not only antioxidative but also anticoagulant properties and may be useful in creation of new therapeutic agents or dietary supplements. Based on described properties polyphenols would be very helpful with both prevention and treatment of thromboembolic complications associated with multiple failures of haemostasis, because the available therapeutic agents do not offer such double-effects (antioxidant and anticoagulant). PMID:27475864

  6. Anticoagulation in pregnant women with prosthetic heart valves.

    PubMed

    Danik, Stephan; Fuster, Valentin

    2004-10-01

    The combination of heart disease and pregnancy can present a formidable challenge to the clinician entrusted to care for both the mother and fetus. Since most data is retrospective, a definitive prognosis for such a patient may be difficult to obtain. Nevertheless, certain cardiac conditions carry greater risks of maternal mortality than do others. However, even for certain preexisting conditions, a tremendous amount of debate persists with respect to risks during pregnancy and optimal peripartum management. One such area of controversy concerns anticoagulation in pregnant women with prosthetic heart valves. For patients who require anticoagulation for mechanical valves, the choice of some combination of warfarin, unfractionated heparin, and low-molecular-weight heparin (LMWH) has resulted in many small-scale trials, which have not yet provided definite guidance as to the best course of action. Even more controversial has been the recent labeling change that advises against the use of LMWH in all patients with prosthetic heart valves, as a result of two cases of prosthetic valve thrombosis in women using LMWH while pregnant. Although the latest product labeling, in the summer of 2003, was changed to a less restrictive recommendation, debate persists. A discussion of the available data on anticoagulation in pregnant women with prosthetic heart valves is presented here, to inform the clinician and the patient of the risks and benefits of the options presently available. PMID:15543433

  7. Anticoagulation in chronic kidney disease patients-the practical aspects.

    PubMed

    Hughes, Stephen; Szeki, Iren; Nash, Michael J; Thachil, Jecko

    2014-10-01

    There is an increasing awareness about the risks of arterial and venous thromboembolism (TE) in hospital patients and general public which has led to consideration of thrombosis prevention measures in earnest. Early recognition of the symptoms of TE disease has led to timely administration of antiplatelet and anticoagulant drugs, translating to better outcome in many of these patients. In this respect, patients with chronic kidney disease (CKD) represent a special group. They indeed represent a high-risk group for thrombosis both in the cardiovascular territory and also in the venous circulation. At the same time, abnormalities in the platelet membranes put them at risk of bleeding which is significantly more than other patients with chronic diseases. Anticoagulation may be ideal to prevent the former, but the co-existing bleeding risk and also that the commonly used drugs for inhibiting coagulation are eliminated by renal pathways pose additional problems. In this review, we try to explain the complex thrombotic-haemorrhagic state of chronic kidney disease patients, and practical considerations for the management of anticoagulation in them with a focus on heparins. PMID:25878775

  8. Utilization of Anticoagulation Therapy in Medicare Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Fitch, Kate; Broulette, Jonah; Pyenson, Bruce; Iwasaki, Kosuke; Kwong, Winghan Jacqueline

    2012-01-01

    Background Clinical guidelines recommend oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) at moderate or high risk for stroke but not at high risk for bleeding; however, studies consistently report suboptimal use of such therapy. This study used Medicare Part D claims data to assess the use of warfarin in the Medicare population. Objectives To compare real-world warfarin utilization with current treatment guideline recommendations, and to assess the effect of warfarin exposure level on patient outcomes in Medicare beneficiaries with nonvalvular AF (NVAF). Methods Patients who were recently diagnosed with NVAF were identified using a random 5% sample of Research Identifiable Files of Medicare beneficiaries in 2006 or 2007. Individuals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of ≥1 warfarin prescription claims within 12 months after the index diagnosis. Warfarin exposure level was assessed by the proportion of days covered during the 12-month follow-up period. The effect of warfarin exposure on ischemic stroke and major bleeding event rates during the 12-month follow-up period were assessed using multivariate logistic regression. Results Data from 14,149 newly diagnosed patients with NVAF (mean age, 79 years; 58.7% female) were analyzed, and of these, 7524 (53.2%) patients were identified as having moderate-to-high stroke risk and not being at high bleeding risk. Of these patients, 3110 (41.3%) did not receive warfarin within 12 months of the index diagnosis. The risk for ischemic stroke was significantly lower in those with warfarin exposure versus no warfarin exposure (adjusted odds ratio [OR], 0.51; confidence interval [CI], 0.43–0.61; P <.001) and in patients with warfarin proportion of days covered ≥80% versus those with proportion of days

  9. Oral cysticercosis.

    PubMed

    Chunduri, Nagendra S; Goteki, Venkateswarulu; Gelli, Vamsi; Madasu, Krishnaveni

    2013-03-01

    Cysticercosis is a common disease in developing countries, but oral lesions caused by this parasitic infestation are rare. We report here a rare case of oral cysticercosis in a 17 year old male who sought treatment for an asymptomatic nodule of the lower lip that had previously been diagnosed as a mucocele. PMID:23691623

  10. X-ray structures of the anticoagulants coumatetralyl and chlorophacinone. Theoretical calculations and SAR investigations on thirteen anticoagulant rodenticides

    NASA Astrophysics Data System (ADS)

    Dolmella, A.; Gatto, S.; Girardi, E.; Bandoli, G.

    1999-12-01

    Coumatetralyl and chlorophacinone, two substances related to 4-hydroxycoumarin (HC) and to 1,3-indandione (ID), respectively, show activity as anticoagulant rodenticides. In the present study we have investigated the solid-state structures of coumatetralyl and chlorophacinone by means of X-ray single-crystal and powder diffraction, along with thermal analysis. The crystal structures of the two compounds have been used as input geometries for a series of computational chemistry efforts, involving other anticoagulant derivatives as well. Thus, ab initio, semiempirical molecular orbital, molecular mechanics and molecular dynamics/simulated annealing calculations have been performed on thirteen anticoagulant rodenticides. In particular, the annealing calculations have been made to assess the conformational freedom of the compounds under scrutiny. All the generated conformers have been classified into families. The classification has first been made empirically, and then validated by means of a cluster analysis. A number of structural and physico-chemical parameters derived from the calculations has been used in turn for structure-activity relationships (SARs) investigations. In the latter, we have assessed how the selected parameters affect toxicity. The results seem to be consistent with a three-dimensional biophore model, in which higher toxicity is predicted for the more voluminous rodenticides. We suggest that these compounds better fit the active site of the target enzyme vitamin K 2,3-epoxide reductase (KO-reductase).

  11. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

  12. Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

    PubMed

    Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

  13. Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

    PubMed

    Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation. PMID:26273933

  14. Variation in Anticoagulant Recommendations by the Guidelines and Decision Tools among Patients with Atrial Fibrillation.

    PubMed

    Shewale, Anand; Johnson, Jill; Li, Chenghui; Nelsen, David; Martin, Bradley

    2015-01-01

    Published atrial fibrillation (AF) guidelines and decision tools offer oral anticoagulant (OAC) recommendations; however, they consider stroke and bleeding risk differently. The aims of our study are: (i) to compare the variation in OAC recommendations by the 2012 American College of Chest Physicians guidelines, the 2012 European Society of Cardiology (ESC) guidelines, the 2014 American Heart Association (AHA) guidelines and two published decision tools by Casciano and LaHaye; (ii) to compare the concordance with actual OAC use in the overall study population and the population stratified by stroke/bleed risk. A cross-sectional study using the 2001-2013 Lifelink claims data was used to contrast the treatment recommendations by these decision aids. CHA₂DS₂-VASc and HAS-BLED algorithms were used to stratify 15,129 AF patients into nine stroke/bleed risk groups to study the variation in treatment recommendations and concordance with actual OAC use/non-use. The AHA guidelines which were set to recommend OAC when CHA₂DS₂-VASc = 1 recommended OAC most often (86.30%) and the LaHaye tool recommended OAC the least often (14.91%). OAC treatment recommendations varied considerably when stroke risk was moderate or high (CHA₂DS₂-VASc > 0). Actual OAC use/non-use was highly discordant (>40%) with all of the guidelines or decision tools reflecting substantial opportunities to improve AF OAC decisions.

  15. [Bleeding, the Achilles' heel in patients treated with anticoagulants. Approach in patients with atrial fibrillation].

    PubMed

    Morais, João

    2012-04-01

    Bleeding is always the Achilles' heel of all antithrombotic therapy, being unthinkable to use this type of therapy ignoring the complications that it may arise. The bleeding risk raises very particular problems, namely how to predict it and how to manage it. The withdrawal of antithrombotic drugs and transfusion are two important practical problems, involving clinical decisions that are generally very difficult. The new oral anticoagulants pose new problems. If on the one hand its bleeding risk appears to be less, specially in what concerns intracranial bleeding and potentially life-threatening bleeding, on the other hand the lack of an antidote or the lack of a quick and effective laboratory test to evaluate its efficacy, are arguments used by the critics. The risk of bleeding is conditioned by several factors, among them old age. The elderly patient is, by definition, the patient that can bleed more but also the one that, due to its ischemic risk, can reap more benefit. In this paper some of the tools used to predict the risk of bleeding and its clinical impact are also presented.

  16. Anticoagulation Quality and Complications of using Vitamin K Antagonists in the Cardiac Surgery Outpatient Clinic

    PubMed Central

    da Costa, Mário Augusto Cray; Krum, Lucas Kraeski; Geraldino, Juliana da Silva; Schafranski, Marcelo Derbli; Gomes, Ricardo Zanetti; Reis, Elise Souza dos Santos

    2016-01-01

    INTRODUCTION: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. OBJECTIVE: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. METHODS: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding) and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. RESULTS: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli); 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001). Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04). Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03), less annual consultations (P=0.02) and less dose adjustments (P=0.003). Patients with longer duration of anticoagulation have more complications (P=0.001). CONCLUSION: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of anticoagulation. PMID:27737407

  17. Ampicillin Oral

    MedlinePlus

    ... capsule, liquid, and pediatric drops to take by mouth. It is usually taken every 6 hours (four ... blood thinners') such as warfarin (Coumadin), atenolol (Tenormin), oral contraceptives, probenecid (Benemid), rifampin, sulfasalazine, and vitamins.tell ...

  18. Oral pathology.

    PubMed

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  19. Oral Cancer

    MedlinePlus

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  20. Oral Health

    MedlinePlus

    ... its box has the American Dental Association's (ADA) seal of acceptance, it is good for your oral ... dispensed solutions have the American Dental Association (ADA) seal. Other over-the-counter whitening products include whitening ...

  1. Oral Cancer

    MedlinePlus

    ... use. Some oral cancers are linked to human papilloma virus (HPV) infections of the mouth and throat. ... The number of oropharyngeal cancers linked to human papilloma virus (HPV) has risen dramatically over the past ...

  2. Sex Differences in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel

    2014-01-01

    Abstract In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice. PMID:25398066

  3. Challenges encountered with argatroban anticoagulation during cardiopulmonary bypass

    PubMed Central

    Agarwal, Shvetank; Ullom, Beth; Al-Baghdadi, Yasser; Okumura, Michael

    2012-01-01

    Use of argatroban as an alternative to heparin during cardiopulmonary bypass (CPB) in patients with heparin-induced thrombocytopenia has gained some attention in the past two decades. Dosing of argatroban during CPB is complex due to lack of complete understanding of its pharmacokinetic profile and the various elements during CPB that may alter its plasma levels. We report a case where the c