Teitel, Jerome M.
Venous thromboembolic diseases are among the most important causes of morbidity and mortality in Canada. Agents which interfere with the coagulation mechanism are highly effective in treating these disorders, but at the potentially high cost of serious hemorrhagic complications. The optimal prevention of both serious outcomes and complications of therapy can be achieved by prophylactic treatment of high risk patients. Heparin and vitamin K antagonists remain the mainstays of antithrombotic therapy. The pharmacology of these agents is reviewed, and a rational approach to their clinical use is presented. PMID:21279098
Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero
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
Harter, Katherine; Levine, Michael; Henderson, Sean O.
Historically, most patients who required parenteral anticoagulation received heparin, whereas those patients requiring oral anticoagulation received warfarin. Due to the narrow therapeutic index and need for frequent laboratory monitoring associated with warfarin, there has been a desire to develop newer, more effective anticoagulants. Consequently, in recent years many novel anticoagulants have been developed. The emergency physician may institute anticoagulation therapy in the short term (e.g. heparin) for a patient being admitted, or may start a novel anticoagulation for a patient being discharged. Similarly, a patient on a novel anticoagulant may present to the emergency department due to a hemorrhagic complication. Consequently, the emergency physician should be familiar with the newer and older anticoagulants. This review emphasizes the indication, mechanism of action, adverse effects, and potential reversal strategies for various anticoagulants that the emergency physician will likely encounter. PMID:25671002
Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe
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
Cundiff, David K
Context On the basis of theoretical rationale, heparoids and vitamin K antagonists are prescribed to prevent complications of venous thromboembolism (VTE, including pulmonary emboli [PE] and deep vein thrombosis [DVT]). They have been employed as the standard of care for treatment of VTE for over 40 years. Objective Critique the evidence supporting the efficacy of anticoagulants for the treatment of VTE in reducing morbidity and/or mortality. Data Sources This includes a search of reference lists and Medline. Study Selection This includes studies concerning the diagnosis and incidence of PE and DVT, efficacy of anticoagulants in preventing complications, risks of anticoagulant therapy, and the costs of diagnosis and the treatment of VTE. Data Extraction I analyzed references cited in reviews and meta-analyses of VTE, and from Medline searches concerning diagnosis and treatment. The data quality and validity of studies depended on the consistency of findings and statistical significance of the data. Data Synthesis No placebo-controlled trials of anticoagulants as treatment of PE with objective criteria for diagnosis have been published. Three randomized trials of anticoagulants vs no anticoagulants in DVT showed no benefit with heparin and vitamin K antagonists (combined all-cause mortality: anticoagulants = 6/66, un-anticoagulated controls = 1/60, P = .07). No placebo-controlled trials of low-molecular-weight heparins or thrombolytic drugs have been done; therefore, their efficacy in VTE depends entirely on randomized comparisons with unfractionated heparin. They have not been proven safer or more efficacious than unfractionated heparin. Thrombolysis causes more major and fatal bleeds than heparin and is no more effective in preventing PE. Diagnosing and treating VTE patients in the United States with anticoagulants costs $3.2 to $15.5 billion per year (1992 dollars). Bleeding and complications of angiography cause 1017-3525 deaths annually. Conclusion
Martí-Fàbregas, J; Delgado-Mederos, R; Mateo, J
Vitamin K antagonists have been shown to be effective in the primary and secondary prevention of systemic and cerebral emboli in patients with cardiac causes of embolism, especially atrial fibrillation. The reduced risk of stroke is greater in secondary prevention, although this reduction is accompanied by an inherent risk of hemorrhagic complications, among which cerebral hemorrhage is especially serious. The therapeutic window of these agents is limited and the best benefit/risk profile is obtained with an INR of between 2 and 3. The anticoagulant effect obtained shows marked variability, requiring frequent clinical and laboratory monitoring of the treatment. The introduction of oral anticoagulants that would aid the administration of these agents with equal or greater efficacy and lower risk is required.
Akagi, Satoshi; Kusano, Kengo Fukushima
Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.
Mariyanovski, Valeri; Hadzhiyska, Valeria
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
Francis, David O; Dang, Jennifer H; Fritz, Mark A; Garrett, C Gaelyn
Indications for antiplatelet and anticoagulation use are expanding. There is no evidence to direct therapeutic management in patients undergoing microlaryngeal surgeries. Our aim was to compare bleeding complications between microlaryngeal surgeries performed for patients preoperatively taken off and maintained on antiplatelet and/or anticoagulation therapy. Retrospective cohort study. Patients undergoing microlaryngeal surgeries (2008-2009) on baseline antiplatelet and/or anticoagulation therapy were identified. Records were reviewed to determine whether therapy was stopped preoperatively. The primary outcome, bleeding complication, was compared between those taken off and maintained on therapy. Patient characteristics, surgical data, and outcomes were assessed. Of 287 microlaryngeal surgeries, 26% were performed for patients on antiplatelet (23%) and/or anticoagulation (3%) therapy. There was no difference in bleeding complications between patients' naïve to and on baseline antiplatelet or anticoagulation therapy [naïve: 3.8% vs. on: 5.3%, P = 0.58] and no thromboembolic events. Among surgeries performed for patients on baseline antiplatelet therapy, 35% preoperatively stopped therapy. No observed difference in bleeding complications was observed between those taken off or maintained on therapy [off: 8.0% vs. on: 4.9%, P = 0.63]. Of 3% of surgeries performed for patients on warfarin, no bleeding complications occurred, even among the 8/10 with therapeutic international normalized ratios. Perioperative management decisions regarding antiplatelet and anticoagulation therapy are becoming more common. Results suggest that antiplatelet therapy can be maintained during microlaryngeal surgery without increasing bleeding risk. Further prospective research is required to confirm findings and rigorously investigate the safety of continuing warfarin and other anticoagulation therapy in these surgeries. 4. © 2013 The American Laryngological, Rhinological and
Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.
Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259
Witt, Daniel M; Sadler, Melanie A; Shanahan, Roberta L; Mazzoli, Georgann; Tillman, Donald J
A growing body of reports has documented the ability of anticoagulation management services to help patients receiving warfarin therapy achieve better outcomes compared to the care provided by their personal physicians (ie, usual care). To compare clinical outcomes associated with anticoagulation therapy provided by a clinical pharmacy anticoagulation service (CPAS) to usual care. Retrospective, observational cohort study, 6 months in duration. Large nonprofit, group-model health maintenance organization. A total of 6,645 patients receiving warfarin therapy were included in the final analyses (intervention group, 3,323 patients; control group, 3,322 patients). Anticoagulation therapy for patients in the intervention group was managed by a centralized, telephonic CPAS. Therapy for patients in the control group was managed in the usual manner by their personal physicians. The primary outcome was the occurrence of anticoagulation therapy-related complications. A secondary outcome was the proportion of time spent in the target international normalized ratio (INR) range for each patient. Cox proportional hazards regression analyses were used to examine the risk of complications in relation to the study group. Patients in the CPAS were 39% less likely to experience an anticoagulation therapy-related complication than were patients in the control group (hazard ratio, 0.61; 95% confidence interval, 0.42 to 0.88). The number of patients needed to treat to prevent an anticoagulation therapy complication was 52. Additional analyses revealed that improved outcomes associated with CPAS were mediated largely through improved therapeutic INR control. Patients in the CPAS group spent 63.5% of study period days within their target INR range compared to 55.2% in the control group (p < 0.001). A centralized, telephonic, pharmacist-managed anticoagulation monitoring service reduced the risk of anticoagulation therapy-related complications compared to that with usual care. The
Herman, W W; Konzelman, J L; Sutley, S H
Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in a patient receiving this therapy. The authors review the topic in depth and offer detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy.
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
Hernández Olmedo, Miguel; Suárez Fernández, Carmen
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.
Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A
To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of
Weibert, R T
The literature on dental surgery in patients receiving oral anticoagulants is reviewed, and methods of managing anticoagulant therapy to minimize the risk of complications are discussed. Although blood loss during and after oral surgery in patients receiving oral anticoagulant drugs can be substantial, research indicates that most bleeding incidents are not serious and can be controlled by local measures. Studies of 241 anticoagulant-treated patients undergoing more than 500 dental extractions during the 1950s and 1960s showed that only 9 had postoperative bleeding. More recent studies indicate that continued anticoagulation can increase the frequency of prolonged bleeding and delay wound healing. An antifibrinolytic mouthwash containing tranexamic acid can effectively suppress postoperative bleeding. Gelatin sponges, oxidized cellulose, and microcrystalline collagen are other useful hemostatic agents. A reduction in the intensity of anticoagulation therapy has been recommended; the prothrombin time should be measured shortly before the procedure in such patients. In many patients the duration of subtherapeutic anticoagulation must be minimized to reduce the possibility of thromboembolism. An option for high-risk patients is to switch them to heparin. Each patient must be evaluated individually, and the level of risk of the dental procedure and the risk of thromboembolism should be taken into account. In patients taking oral anticoagulants who must undergo dental surgery, careful control of the intensity of anticoagulation and improved methods of local hemostasis can minimize the risk of hemorrhagic complications and thromboembolism.
Yoshioka, Daisuke; Toda, Koichi; Hidaka, Takayuki; Yasuda, Soichiro; Saito, Shunsuke; Domae, Keitaro; Sawa, Yoshiki
Anticoagulation therapy with warfarin is essential for postoperative management in patients with left ventricular assist device (LVAD). In this manuscript, we report the case of a patient who developed warfarin resistance after LVAD implantation. Although we administered a novel anticoagulant drug in addition to warfarin and aspirin therapy, the patient developed a major stroke. The patient needed continuous intravenous heparinization until heart transplantation for approximately 2 years. Meticulous management of anticoagulation therapy is essential for a LVAD with warfarin resistance. To our best knowledge, our case is the first case of warfarin resistance in a patient with LVAD.
Dang, Jennifer H; Liou, Nelson Eddie; Ongkasuwan, Julina
Vocal fold movement impairment (VFMI) due to neuronal injury occurs in 20% to 30% of surgeries in the region of the aortic arch. Early injection laryngoplasty can aid with postoperative pulmonary toilet in these high-risk cardiovascular patients. The purpose of this study is to determine whether continuing antiplatelet and anticoagulation therapy during awake transcervical injection laryngoplasty surgery is safe, and if there is any increase in bleeding complications in these patients. This is a retrospective review of patients undergoing awake injection laryngoplasty surgery for VFMI between 2013 and 2016 at a tertiary academic center specializing in aortic and mediastinal diseases. Records were reviewed for patients regarding baseline antiplatelet or anticoagulation therapy, and whether these medications were stopped or continued preoperatively. The primary outcome was bleeding complications. Of the 95 surgeries reviewed, 44 (46%) were performed for patients on antiplatelet therapy, and 71 (75%) for patients on anticoagulation therapy. None of the patients on antiplatelet therapy had their treatment discontinued. Of the patients on anticoagulation, 13 (16.4%) had their therapy held prior to surgery. There was no observed difference in bleeding complications between patients who were continued on antiplatelet or anticoagulation treatment versus those whose therapy was withheld. These results suggest that patients undergoing awake transcervical injection laryngoplasty for VFMI can be maintained on antiplatelet or anticoagulation therapy without increased risk of bleeding. Further larger studies are needed to confirm these findings. 4. Laryngoscope, 127:1850-1854, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.
Dahlberg, Katherine Willett
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
Yasaka, Masahiro; Okada, Yasushi
Novel anticoagulants including dabigatran and rivaroxaban have lower incidence of intracranial hemorrhage compared to warfarin. Therefore, in patients with high risks for intracranial hemorrhage, such as past history of brain infarction, brain hemorrhage, microbleeds on MRI, or concomitant use of antiplatelet, novel anticoagulant may be appropriate. Irrespective of any anticoagulants, it is essential to manage controllable risk factors, such as hypertension, diabetes mellitus, smoking habit, and excessive alcohol drinking. Combination therapy of other antithrombotic agents had better be avoided as long as possible. In emergency of hemorrhage complications, discontinuation of anticoagulants, procedure to stop bleeding, and appropriate intravenous infusion is quite important and lowering blood pressure is also important when intracranial hemorrhage happens. There is no antidote to novel anticoagulants. However, oral activated charcoal may be effective if early after taking medicine. The dabigatran can be dialysed. Some experimental evidences support the role of prothrombin complex concentrate to stop bleeding. However, their usefulness in clinical setting has not been established. Collecting and analyzing data regarding immediate reversal of novel anticoagulants is required in near future.
Mousa, Shaker A
Currently, there are several lines of evidence supporting the interplay between coagulation and inflammation in the propagation of various disease processes, including venous thromboembolism (VTE) and inflammatory diseases. Major advances in the development of oral anticoagulants have resulted in considerable progress toward the goal of safe and effective oral anticoagulants that do not require frequent monitoring or dose adjustment and have minimal food/drug interactions. Indirect inhibitors such as low-molecular-weight heparin (LMWH) and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of VTE, constituting a more targeted anticoagulant approach with predictable pharmacokinetic profiles and no requirement for monitoring. Vitamin K antagonist, with its inherent limitations in terms of multiple food and drug interactions and frequent need for monitoring, remains the only oral anticoagulant approved for long-term secondary thromboprophylaxis in VTE. The oral-direct thrombin inhibitor ximelagatran was withdrawn from the world market due to safety concerns. Newer anticoagulant drugs such as parenteral pentasaccharides (idraparinux, SSR126517E), novel oral-direct thrombin inhibitors (dabigatran), oral-direct factor Xa inhibitors (rivaroxaban, apixaban, YM-150, DU-176b), and tissue factor/factor VIIa complex inhibitors have been "tailor-made" to target specific procoagulant complexes and have the potential to greatly expand oral antithrombotic targets for both acute and long-term treatment of VTE, acute coronary syndromes, and for the prevention of stroke in atrial fibrillation patients.
Nowak-Göttl, U; Langer, F; Limperger, V; Mesters, R; Trappe, R U
Oral anticoagulants [Vitamin-K-Antagonists, Dabigatran, Rivaroxaban, Apixaban] or antiplatelet agents [Aspirin, Clopidogrel, Prasugrel, Ticagrelor] are effective in preventing thromboembolic diseases. In case of interventional of surgical procedures patients with indications for chronic anticoagulation [atrial fibrillation, valve prosthesis, venous thromboembolism] or use of antiplatelet agents [cerebrovascular events, cardiovascular events] will require interruption of antithrombotic/antiplatelet therapy with the need of replacement with a short-acting agent. Due to limited data available from randomized studies and meta-analyses the evidence level is low in the majority of recommendations. Therefore for each patient the bleeding and thrombosis risk depending on the individual patient constitution and the planned intervention must be weighted. In patients with an intermediate risk for thrombosis the bleeding risk of the scheduled intervention will influence the bridging recommendation: In patients with a low bleeding risk oral anticoagulation/antiplatelet therapy can be continued or reduced in intensity. In patients with an intermediate or high bleeding risk along with a low thrombosis risk a temporary interruption of the anticoagulation/antiplatelet therapy is feasible. In patients with a high thrombosis and bleeding risk anticoagulation should be bridged with unfractionated heparin [renal insufficiency] or low molecular weight heparin. In the latter risk situation, inhibition of platelet function can be achieved with short-lasting GPIIb-IIIa inhibitors [Eptifibatide, Tirofiban]. Prior to intervention patients treated with the new oral anticoagulants [Dabigatran; Rivaroxaban; Apixaban] are requested to temporary interrupt the anticoagulation depending on the individual drug half-life and their renal function. Bridging therapy with heparin prior to intervention is not necessary with the new oral anticoagulants.
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
So, Charlotte H; Eckman, Mark H
The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Of 948 patients receiving OAC, 430 (45 %) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49 and 42 % of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27 % had a diagnosis of CAD and 14 % had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn't discontinued. A surprisingly large proportion of patients (22.8 %) had no obvious indication for dual therapy. Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events.
Jonas, Daniel E; Bryant Shilliday, Betsy; Laundon, W Russell; Pignone, Michael
Most patients receiving warfarin are managed in outpatient office settings or anticoagulation clinics that require frequent visits for monitoring. To measure the amount and value of time required of patients for chronic anticoagulation therapy with warfarin. /Participants. Prospective observation of a cohort of adult patients treated at a university-based anticoagulation program. Measurements. Participants completed a questionnaire and a prospective diary of the time required for 1 visit to the anticoagulation clinic, including travel, waiting, and the clinic visit. The authors reviewed subjects' medical records to obtain additional information, including the frequency of visits to the anticoagulation clinic. They used the human capital method to estimate the value of time. Eighty-five subjects completed the study. The mean (median) total time per visit was 147 minutes (123). Subjects averaged 15 visits per year (14) and spent 39.0 hours (29.3) per year on their visits. Other anticoagulation-related activities, such as communication with providers, pharmacy trips, and extra time preparing food, added an average of 52.7 hours (19.0) per year. The mean annual value of patient time spent traveling, waiting, and attending anticoagulation visits was $707 (median $591). The mean annual value when also including other anticoagulation-related activities was $1799 (median $1132). The time required of patients for anticoagulation visits was considerable, averaging approximately 2.5 hours per visit and almost 40 hours per year. for reducing patient time requirements, such as home-based testing, could reduce costs for patients, employers, and companions.
Nerli, R B; Reddy, M N; Devaraju, S; Hiremath, M B
Percutaneous nephrolithotomy (PCNL) is an integral component in the management of large volume renal stone disease either as monotherapy or in combination with shock wave lithotripsy. Stone disease in patients on chronic anticoagulation/antiplatelet therapy, however, poses a difficult scenario. Bleeding is a major concern for any patient undergoing PCNL. We retrospectively analyzed our series of patients with renal calculi who were on chronic anticoagulant therapy and who underwent PCNL. We reviewed the case records of patients undergoing PCNL during the period from January 2005 to December 2011. We analyzed the changes in preoperative and postoperative hemoglobin, serum creatinine, and clotting parameters, as well as intraoperative and postoperative bleeding and thromboembolic complications. During the 5-year study period, a total of 36 patients (30 males and 6 females) with a mean age of 46.33±9.96 years (range, 29-61 years) who were on chronic anticoagulant/antiplatelet therapy underwent PCNL for urolithiasis. The mean size of the stone was 6.40±1.98 cm(2) (range, 2.8-9 cm(2)). The mean operating time was 62.08±10.10 min. The bleeding was successfully managed in all patients and the anticoagulant/antiplatelet agents were restarted after an appropriate duration. The mean rise in serum creatinine at discharge was 0.05±0.03 mg/dl and the mean fall in serum hemoglobin was 1.63±0.77 g/dl. At 3 months after surgery, the stone-free rate was 100%. With careful preoperative care and regulation of anticoagulation/antiplatelet therapy and appropriate intraoperative management, PCNL can be performed safely and successfully in properly selected patients with renal calculi who are on chronic anticoagulant/antiplatelet therapy.
Jonas, Daniel E.; Shilliday, Betsy Bryant; Laundon, W. Russell; Pignone, Michael
Background Most patients receiving warfarin are man- aged in outpatient office settings or anticoagulation clinics that require frequent visits for monitoring. Objective To measure the amount and value of time required of patients for chronic anticoagulation therapy with warfarin. Design/Participants Prospective observation of a cohort of adult patients treated at a university-based anticoagulation program. Measurements Participants completed a questionnaire and a prospective diary of the time required for 1 visit to the anticoagulation clinic, including travel, waiting, and the clinic visit. The authors reviewed subjects’ medical records to obtain additional information, including the frequency of visits to the anti- coagulation clinic. They used the human capital method to estimate the value of time. Results Eighty-five subjects completed the study. The mean (median) total time per visit was 147 minutes (123). Subjects averaged 15 visits per year (14) and spent 39.0 hours (29.3) per year on their visits. Other anticoagulation-related activities, such as communication with providers, pharmacy trips, and extra time preparing food, added an average of 52.7 hours (19.0) per year. The mean annual value of patient time spent traveling, waiting, and attending anticoagulation visits was $707 (median $591). The mean annual value when also including other anticoagulation-related activities was $1799 (median $1132). Conclusions The time required of patients for anticoagulation visits was considerable, averaging approximately 2.5 hours per visit and almost 40 hours per year. Methods for reducing patient time requirements, such as home-based testing, could reduce costs for patients, employers, and companions. PMID:19773584
González Bárcenas, Martha L; Pérez Aisa, Ángeles
The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
Saour, J N; Ali, H A; Mammo, L A; Sieck, J O
Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.
Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P
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
Grzybowski, Andrzej; Kupidura-Majewski, Konrad; Kupidura, Paulina
The number of elderly patients using anticoagulant and antiplatelet treatment in prevention of thromboembolism has significantly increased in recent years. It was believed for many years that those patients may be at higher risk for hemorhages during ocular surgery. Different strategies were proposed to prevent these complications, including discontinuation of anticoagulants, dose reduction, or substitution with low molecular weight heparin. The objective of this work was to evaluate the results of studies presenting the results of vitreoretinal surgeries in patients continuing antiplatelet and/or anticoagulant treatment. We performed a PubMed search of possible intraoperative and postoperative hemorrhages in patients receiving anticoagulant and/or antiplatelet therapy during vitreoretinal surgery in 2007-2014. In most of the studies reviewed there was no substantial increase in intraoperative and postoperative hemorrhages risks during vitreoretinal surgery. However, in some studies, a substantially increased risk has been identified. We conclude that the available data is insufficient to decide whether to continue or discontinue anticoagulant and/or antiplatelet therapy during vitreoretinal surgery and we recommend an individualized approach in consultation with the patient's medical doctors and anesthesiologists.
ten Berg, Jurriën M; Plokker, HW Thijs; Verheugt, Freek WA
Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used.
ten Berg, Jurriën M; Plokker, HW Thijs; Verheugt, Freek WA
Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used. PMID:11806786
Spyropoulos, Alex C
The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.
Horstkotte, Dieter; Piper, Cornelia
Thromboembolic complications after valve replacement are significantly reduced if the INR is increased from 1.0 to 2.0. Hemorrhagic events increase exponentially with more intensive oral anticoagulation. In INR (patient) self-testing (PST), patients self-check their INR after being appropriately educated and supplied with a coagulometer. Patients contact their home physician if the actual INR tends to run outside an individually defined target INR corridor for correction. For patient self-management (PSM), subjects are trained to self-test their INR and to adjust the anticoagulant dose according to their anticoagulation state. The median difference between self-tested and laboratory-tested INRs was < 5.0%, indicating no significant differences between the two methods. PSM resulted in a significantly more stable oral anticoagulation therapy (OAT), which was the strongest predictor for a low complication rate after valve replacement surgery. Lower rates of thromboembolism (0.9 versus 3.6% per patient-year; pt-yr) and bleeding (4.5 versus 10.9% per pt-yr) (p < 0.001) were seen in PSM subjects than with conventional INR management. A switch from conventional to PSM resulted in a 30% reduction in complication rates in the German Experience with Low Intensity Anticoagulation (GELIA) study. After appropriate education and provision with a handy coagulometer, the vast majority of patients after valve replacement can self-check INRs and adjust the anticoagulant dosage accordingly. PSM results in a significantly more stable oral anticoagulation treatment and consequently in lower incidences of thromboembolic and bleeding events.
Gunasekaran, Kulothungan; Rudd, Kelly M.; Murthi, Swetha; Kaatz, Scott; Lone, Nazir
Even though highly vascularized, the thyroid gland rarely has spontaneous bleeding. Bleeding into the thyroid gland can result in potentially lethal acute airway compromise. This case report describes an elderly patient on warfarin for atrial fibrillation, who presented with swelling on the right side of her neck causing acute airway obstruction. An urgent computed tomography of the neck showed an enlarging hemorrhage into the right lobe of the thyroid gland. She was initially intubated for airway protection and her anticoagulation was reversed to stop the bleeding. She was closely monitored in the intensive care unit. After an uncomplicated tracheal extubation and recovery, she was discharged and scheduled for an elective total thyroidectomy. We desire that physicians be aware of this rare, potentially lethal bleeding complication. PMID:28243434
Trujillo-Santos, Javier; Nieto, José Antonio; Ruíz-Gamietea, Angeles; López-Jiménez, Luciano; García-Bragado, Ferran; Quintavalla, Roberto; Monreal, Manuel
Cancer patients with venous thromboembolism (VTE) have an increased incidence of bleeding complications while on anticoagulant therapy. RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for major bleeding. Up to May 2009, 4,709 patients with active cancer had been enrolled in RIETE registry. During the first 3 months of anticoagulant therapy, 200 (4.2%) patients developed major bleeding. Then, 38 (0.8%) further patients bled beyond the first 90 days of therapy, 3 bled after withholding anticoagulant therapy. The most common sites of bleeding were the gastrointestinal tract (118 patients, 49%), genitourinary system (43 patients, 18%) and the brain (27 patients, 11%). In all, 160 patients (66%) died within 30 days after bleeding: 88 (55%) died of bleeding, 3 (1.9%) died of recurrent pulmonary embolism. Major bleeding is a frequent and severe complication in cancer patients with VTE, even beyond the third month. One third of the patients who bled died due the bleeding event.
Mierzynski, Radzisław; Poniedzialek-Czajkowska, Elzbieta; Kimber-Trojnar, Zaneta; Leszczynska-Gorzelak, Bozena; Oleszczuk, Jan
Pregnancy is a specific state of heightened coagulability related to the increase in procoagulant agents and to the reduced fibrinolysis. Pregnancy is associated with a 4-fold increased risk of developing venous thromboembolism (VTE) and this risk still increases to 14-fold during puerperium. A correlation between the metabolic syndrome and development of cardiovascular events and cerebrovascular incidents has been described. Such a relationship is referred to a hypercoagulable state due to increased serum levels of the plasminogen activator inhibitor-1 (PAI-1), fibrinogen, factor (F) VII and VIII, von Willebrand factor and from endothelial activation, caused by increased circulating adhesion molecules. As to the risk of VTE, the probability for its association with cardiovascular incidents is increased by common underlying mechanisms such as the activation of platelets and the blood coagulation. A correlation between idiopathic VTE and the metabolic syndrome has been reported. The anticoagulant therapy may be recommended during the pregnancy for the treatment or the prophylaxis of VTE and, in women with artificial heart valves, for the prevention of the valve thrombosis and systemic embolisation. There are also specific conditions during pregnancy which benefit from anticoagulant use, such as recurrent fetal loss, thrombophilia and assisted reproductive technology. There are no published specific data about using of anticoagulant agents in pregnant patients with the metabolic syndrome except for a few articles addressing reproductive problems. The mechanisms of anticoagulant action were studied with the focus on heparinoids, because of their safety not only for the patient but also for the fetus. The new oral anticoagulants were also shortly described although they have been contraindicated during the pregnancy.
Pandya, Ekta Y; Bajorek, Beata
The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present
Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.
Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323
Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk
Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12–16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well. PMID:28042559
Park, Hyun Oh; Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Yang, Jun Ho; Lee, Chung-Eun; Kim, Jong-Duk
Hypercoagulable states have been associated with aortic thrombosis. Antiphospholipid syndrome (APS) is one of the commonest types of acquired thrombophilia. We report the case of successful anticoagulation management in an APS patient with mobile thrombi within the aorta. A 58-year-old male patient presented to the emergency department (ED) with right-sided hemiparesis. His first symptoms were noted approximately 12-16 hours before presentation to the ED. Magnetic resonance imaging of the brain showed acute embolic infarction of the left frontal and parietotemporal lobes. Transesophageal echocardiography (TEE) and computed tomography angiography (CTA) demonstrated mobile thrombi attached to the wall of the ascending aorta and aortic arch. The patient was diagnosed with APS based on positivity of anti-beta-2 glycoprotein 1 antibodies, and was initiated on anticoagulation therapy. Repeated TEE and CTA revealed complete resolution of the thrombi after 12 days of treatment; the patient was discharged well.
Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva
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.
Toth, Peter P
Background Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Methods Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. Conclusion NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism. PMID:26929637
Davis, T Keefe; Neumayr, Tara; Geile, Kira; Doctor, Allan; Hmeil, Paul
To provide the pediatric intensivist an in-depth understanding of citrate as regional anticoagulant during continuous renal replacement therapy. We searched the PubMed.gov database using the initial key words: citrate anticoagulation [title] AND continuous; citrate [title] AND pediatric AND continuous; prospective pediatric renal replacement AND citrate; and regional citrate anticoagulation. Additional searchers were performed using EMBASE, CINAHL, and SCOPUS with similar keywords and limits. Further articles were gathered from bibliographic references of relevant studies and reviews. Only articles published in English were reviewed. In the pediatric population, there are no prospective interventional or randomized studies comparing regional versus systemic anticoagulation. However, there are 11 (retrospective and prospective observational studies) in the pediatric population using citrate anticoagulation. These studies have shown that regional citrate anticoagulation in the pediatric population can be effective, provide equivalent circuit survival, and decrease bleeding compared with heparin anticoagulation. In the adult population, there are six prospective randomized controlled trials comparing the efficacy of regional citrate anticoagulation versus heparin. Two systematic reviews with meta-analysis of these six trials have been performed. The adult data on the use of regional citrate anticoagulation during continuous renal replacement therapy show a decreased risk of bleeding and at the least equivalent circuit survival as compared to heparin. Current pediatric and adult studies support regional citrate anticoagulation as an effective alternative to systemic heparin anticoagulation in most patient populations. Continuous renal replacement therapy is the most common modality of renal replacement in the critical care setting. Regional anticoagulation is an ideal option in a critically ill child after recent surgery or with coagulopathy. Therefore, regional
Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe
The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.
Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus
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
Cantin, Ariane; Lahaie, Alexandre; Odobasic, Bojan; Tremblay, Marie-Philip; Wazzan, Dana; Caron, Stéphanie; Leblanc, Caroline; Martineau, Josée; Lalonde, Lyne
Background: The ACO Program (Programme ACO), a continuous quality improvement program (CQIP) in anticoagulation therapy, was offered in community pharmacies as a pilot project. Objective: To evaluate the participants’ appreciation for the various activities of the program. Methods: Participants had access to training activities, including an audit with feedback, online training activities (OTA), clinical tools and support from facilitators. Cognitive behavioural learning determinants were evaluated before and 5 months after the beginning of the program. Participants’ satisfaction and perception were documented via online questionnaires and a semistructured interview. Results: Of the 52 pharmacists in the ACO Program, 47 participated in this evaluation. Seventy-seven percent of the participants completed at least 1 OTA and 6% published on the forum. The feeling of personal effectiveness rose from 8.01 (7.67-8.35) to 8.62 (8.24-8.99). The audit and feedback, as well as the high-quality OTA and their lecturers, were the most appreciated elements. Discussion: There was a high OTA participation rate. The facilitators seemed to play a key role in the CQIP. The low level of participation in the forum reflects the known phenomenon of social loafing. Technical difficulties affecting the platform and data collection for the audit with feedback constituted limitations. Conclusion: The CQIP in anticoagulation therapy is appreciated by community pharmacists and is associated with an improved feeling of personal effectiveness. PMID:27829859
Somma, Francesco; Grande, Nicola Maria; Plotino, GianLuca; Cameli, Giorgio; Pameijer, Cornelis H
This clinical study reviewed dental surgical extractions that were performed on 532 patients diagnosed at risk of thromboembolism without interrupting their anticoagulant therapy. The results confirmed that anticoagulant therapy can be modified successfully and does not need to be interrupted, which can carry significant risks.
Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel
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
Krasny, Marta; Krasny, Kornel; Fiedor, Piotr
Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.
Lopes, Antonio Augusto
In pulmonary hypertension (PH), thrombosis and thromboembolism may occur as primary events associated with inherited or acquired thrombophilia. Alternatively, in situ thrombosis may develop as a complication of pre-existing vasculopathy as in the case of idiopathic PH and related disorders (so called pulmonary arterial hypertension). In these disorders, a number of abnormalities has been described involving endothelial cells, platelets and other circulating cellular and soluble elements. These abnormalities are suggestive of a shift of pulmonary vascular microenvironment toward a procoagulant, prothrombotic and antifibrinolytic pattern. The abnormalities described so far include circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P-selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and cytokines. Also, decreased endothelial production of natural anticoagulants (thrombomodulin) and platelet antiaggregating substances (nitric oxide, prostacyclin) have been demonstrated. The present review is focused on the procoagulant, prothrombotic and antifibrinolytic mechanisms so far identified in PH, in both clinical setting and animal models. Understanding of these mechanisms is crucial for a proper selection of anticoagulant and antithrombotic therapies and provides the rationale for development of novel therapeutic options.
de Vicente Cámara, M P; Lucía Cuesta, J F; Aguilar Franco, C; Solano Bernad, V; Serrano González, C; García-Erce, J A
The incidence of major thromboembolic complications in patients on oral anticoagulant therapy (OAT) and the correlation of this with the intensity of the OAT and the INR level at the time of the episode have been assessed in our study. We have carried out a retrospective study including 1350 patients with an overall follow-up period of 6432 patient-years. The mean INR level throughout OAT and at the time of the mayor thromboembolic event were considered. The statistical analysis was performed by means of a survival analysis test. The incidence of major thromboembolic complications found in our study was 1.18/100 patient-years. Those patients with a mean INR below the therapeutic range showed significantly a higher risk (3.31 times higher) of suffering from some sort of major thromboembolic complication. Mean INR level at the time of the event was 1.9 and 47% of those patients had an INR level < 2 at the time of the thromboembolic complication. The probability of suffering a major thromboembolic complication for those subjects on OAT increases as the INR falls below the therapeutic range; therefore we must pay special attention to this factor in order to avoid any further recurrences.
Thean, D; Alberghini, M
Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment.
Zullo, Angelo; Hassan, Cesare; Radaelli, Franco
Periprocedural management of antithrombotics for gastrointestinal endoscopy is a common clinical issue, given the widespread use of these drugs for primary and secondary cardiovascular prevention. For diagnostic procedures, with or without biopsy, no adjustments in antithrombotics are usually needed. For operative procedures, balancing the risk of periprocedural hemorrhage with the continuation of antithrombotics against the chance of recurrent thromboembolic events with their discontinuation may be challenging. Oral anticoagulants need to be temporarily withheld, and consideration must be given to whether a periendoscopic “bridge” therapy, typically a low-molecular-weight heparin, should be used in order to minimize the risk of thromboembolic events. Although some emerging evidence has shown that patients receiving heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to controls, bridging therapy is still recommended for patients on vitamin K antagonists who are at high thrombotic risk. Conversely, bridging therapy is usually not needed for patients taking new oral agents, which are characterized by shorter half-lives, and a rapid offset and onset of action. Management of antiplatelet therapy requires special care in patients on secondary prevention, especially those with coronary stents. This review is intended to summarize the recommendations of updated International Guidelines designed to help the decision-making process in such an intricate field. PMID:28042233
Isola, G; Matarese, G; Cordasco, G; Rotondo, F; Crupi, A; Ramaglia, L
Patients treated with oral anticoagulant therapy (OAT) represent an issue to the dentist, as an increasing number of people are using anticoagulant drugs for cardiovascular disease. The choice of an eventual suspension or continuation of anticoagulant therapy is important when considering an efficient management of the patient. Patients in anticoagulant therapy and requiring dental procedures sometimes represent therapeutic concerns especially concerning the suspension of the anticoagulant treatment. At the moment there is no consensus among international experts of a possible discontinuation of therapy before invasive dental procedures. In this paper, the authors try to focus on this topic through a critical review of the literature. Most of the studies suggest the continuation of the anticoagulant treatment with heparin before invasive oral surgical interventions. Based on the data of the literature, two rules must be adopted in clinical practice: 1) maintenance of anticoagulation related to the international normalized ratio (INR); 2) local application of antifibrinolytic agents to ensure a proper hemostatic process. Given the widespread use of anticoagulant drugs in cardiovascular disease, dentists must often face the problem of the therapy and, since there is no consensus on the management of these patients, the authors propose, after a thorough critical review of the literature, the implementation of a multiphase protocol of surgical approach to be implemented with safety in daily clinical practice.
Soltysiak, Jolanta; Warzywoda, Alfred; Kociński, Bartłomiej; Ostalska-Nowicka, Danuta; Benedyk, Anna; Silska-Dittmar, Magdalena; Zachwieja, Jacek
Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± 5.63 kg. RCA-CRRT was performed with a commercially available pre-dilution citrate solution (Prismocitrate 18/0). The mean time on RCA-CRRT and HA-CRRT was 148.73 ± 131.58 and 110.24 ± 105.38 h, respectively. Circuit lifetime was significantly higher in RCA-CRRT than in HA-CRRT (58.04 ± 51.18 h vs. 37.64 ± 32.51 h, respectively; p = 0.030). Circuit clotting was observed in 11.63 % of children receiving RCA-CRRT and 34.15 % of those receiving HA-CRRT. Episodic electrolyte and metabolic disturbances were more common in children receiving RCA-CRRT. The survival at discharge from the hospital was 37.5 and 14.3 % among children receiving RCA-CRRT and HA-CRRT, respectively. In critically ill children with a low body weight, RCA appeared to be safe and easy to used. Among our patient cohort, RCA was more effective in preventing circuit clotting and provided a better circuit lifetime than HA.
Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Lip, Gregory Y H; Lam, Karen Siu-Ling; Tse, Hung-Fat; Siu, Chung-Wah
Existing data on the risk of ischemic stroke in hyperthyroidism-related atrial fibrillation (AF) and the impact of long-term anticoagulation in these patients, particularly those with self-limiting AF, remain inconclusive. Risk of stroke in hyperthyroidism-related AF is the same as nonhyperthyroid counterparts. This was a single-center observational study of 9727 Chinese patients with nonvalvular AF from July 1997 to December 2011. Patients with AF diagnosed concomitantly with hyperthyroidism were identified. Primary and secondary endpoints were defined as hospitalization with ischemic stroke and intracranial hemorrhage in the first 2 years. Patient characteristics, duration of AF, and choice of antithrombotic therapy were recorded. Self-limiting AF was defined as <7 days' duration. Out of 9727 patients, 642 (6.6%) had concomitant hyperthyroidism and AF at diagnosis. For stroke prevention, 136 and 243 patients (21.1% and 37.9%) were prescribed warfarin and aspirin, respectively, whereas the remaining patients (41.0%) received no therapy. Ischemic stroke occurred in 50 patients (7.8%), and no patient developed hemorrhagic stroke. Patients with CHA2 DS2 -VASc of 0 did not develop stroke. Warfarin effectively reduced the incidence of stroke compared with aspirin or no therapy in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF, but not in those with self-limiting AF or CHA2 DS2 -VASc of 0. Presence of hyperthyroidism did not confer additional risk of ischemic stroke compared with nonhyperthyroid AF. Patients with hyperthyroidism-related AF are at high risk of stroke (3.9% per year). Warfarin confers stroke prevention in patients with CHA2 DS2 -VASc ≥1 and non-self-limiting AF. Overall stroke risk was lower in hyperthyroid non-self-limiting AF patients compared with nonhyperthyroid counterparts. © 2015 Wiley Periodicals, Inc.
Zektser, Miri; Bartal, Carmi; Zeller, Lior; Nevzorov, Roman; Jotkowitz, Alan; Stavi, Vered; Romanyuk, Vitaly; Chudakov, Gregory; Barski, Leonid
Objective The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options. Methods A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson’s index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE. Results We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson’s score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson’s score index there were no significant differences in primary outcomes. Conclusion Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy. PMID:27487310
Lippert, S; Gutschik, E
By administering a questionnaire to 253 patients with cardiac-valve prostheses (89.3% responding), and another to 136 of their attending dentists (79% responding), the level of knowledge among both groups of anticoagulant therapy in connection with dental treatment was investigated. The cardiothoracic department monitored all anticoagulation therapies. Of the anticoagulated patients, 96.6% were able to state their medication (94.1% received phenprocoumon); and of 86 dentists with patients on anticoagulation treatment, 94% were aware of their patients' medication. All 20 dentists stating that their patients did not receive anticoagulants were correct. The great majority (98%) of the dentists employed a special measure to reduce the risk of bleeding associated with invasive dental procedures, most commonly (86%) referring patients to their general practitioner or hospital department for adjustment of the anticoagulant therapy. Around 60% of the dentists considered extractions and operations to require measures to reduce the risk of bleeding complications. We recommend referral of patients to the attending physician for adjustment of anticoagulation to a target International Normalized Ratio (INR) of 4.0 or possibly 3.0 before undergoing dental procedures involving the risk of bleeding. Additional reduction of the bleeding risk can be obtained by local application of an inhibitor of fibrinolysis (tranexamic acid).
Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José
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.
Taherkhani, Maryam; Taherkhani, Adineh; Hashemi, Seyed Reza; Faghihi Langroodi, Taraneh; Sadeghi, Roxana; Beyranvand, Mohammadreza
The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE) remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE. We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin (1 mg/kg twice a day)] plus a thrombolytic [Alteplase (100 mg) or Streptokinase (1500000 u/2 hours)] or an anticoagulant [Enoxaparin (1 mg/kg twice a day)] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month. Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.022). At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.018); however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association (NYHA) functional class between the two groups at the end of the first month (p value = 0.213). No fatal bleeding or cerebral bleeding occurred in the patients receiving an
Taherkhani, Maryam; Taherkhani, Adineh; Hashemi, Seyed Reza; Faghihi Langroodi, Taraneh; Sadeghi, Roxana; Beyranvand, Mohammadreza
Abstract Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE) remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE. Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin (1 mg/kg twice a day)] plus a thrombolytic [Alteplase (100 mg) or Streptokinase (1500000 u/2 hours)] or an anticoagulant [Enoxaparin (1 mg/kg twice a day)] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month. Results: Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.022). At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.018); however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association (NYHA) functional class between the two groups at the end of the first month (p value = 0.213). No fatal bleeding or cerebral bleeding
Brown, Deanna G; Wilkerson, Eric C; Love, W Elliot
Dermatologic surgeons will increasingly encounter patients on novel oral antiplatelet and anticoagulant medications. We conducted a complete overview of the pharmacokinetics, pharmacodynamics, and side effects of traditional and novel oral anticoagulant and antiplatelet therapies along with dietary supplements with anticoagulant or antiplatelet properties. A PubMed search was completed for "aspirin," "warfarin," "clopidogrel," "dabigatran," "rivaroxaban," "apixaban," "prasugrel," and "ticagrelor." Review articles and publications emphasizing perioperative management of oral anticoagulant or antiplatelet medications were selected. An additional PubMed search was completed for "hemorrhage," "bleeding," and "thrombosis" in conjunction with "dermatology," "dermatologic surgery," and "cutaneous surgery." Aspirin, clopidogrel, and warfarin have shortfalls in dosing, monitoring, and efficacy. Several trials show superior efficacy with dabigatran, rivaroxaban, and apixaban, with equal or reduced risk of bleeding compared with warfarin. Prasugrel and ticagrelor may be associated with an increased bleeding risk. Many over-the-counter medications also have anticoagulant properties with associated bleeding risks that cannot be overlooked. There are few publications evaluating the novel oral anticoagulants' effects on outpatient surgical procedures. Novel anticoagulant and antiplatelet drugs are revolutionizing therapy for cardiovascular diseases. As these medications become more prevalent, dermatologists and dermatologic surgeons must be mindful of the bleeding risk that will apply in our everyday practices. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Kovac, Mirjana; Mikovic, Zeljko; Mitic, Gorana; Djordjevic, Valentina; Mandic, Vesna; Rakicevic, Ljiljana; Radojkovic, Dragica
The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.
Ercan, Metin; Bostanci, Erdal B; Ozer, Ilter; Ulas, Murat; Ozogul, Yusuf B; Teke, Zafer; Akoglu, Musa
Among patients on long-term anticoagulant therapy who undergo laparoscopic cholecystectomy (LC), bleeding complications have not been extensively investigated. The objective of this study was therefore to investigate postoperative bleeding complications prospectively in patients on chronic oral anticoagulation. In the period of January 2002 to December 2007, 44 patients on long-term anticoagulation with warfarin, an oral anticoagulant (OAC), underwent LC in our center. Oral anticoagulant was discontinued 5 days before the planned date of surgery, and patients were admitted to the hospital 3 days before. Upon admission, bridging anticoagulation with enoxaparin, a low molecular weight heparin (LMWH), was started. When their international normalized ratio (INR) decreased to <1.5, patients underwent LC. In the absence of postoperative bleeding complications, OAC and LMWH were resumed on the evening of the day of surgery, and LMWH was continued until each patient's target INR was reached. A comparison group was comprised by 1,421 consecutively enrolled patients with no comorbid disease who underwent LC during the same period. In the comparison group, postoperative bleeding was encountered in 21 patients (1.5%). In the anticoagulation group, postoperative bleeding was encountered in 11 patients (25%) and ranged from minor oozing from a port incision in one patient to hemorrhage, sepsis, and fatality in one patient. In the anticoagulation group, no significant differences were found between patients with and without postoperative bleeding in terms of age, gender, body mass index, American Society of Anesthesiologists score, INR, or other hemostasis parameters. In patients who underwent LC with bridging anticoagulation, postoperative bleeding was markedly more frequent than expected and was not predicted by the usual coagulation parameters. This suggests a need for methods that can indicate which patients on long-term anticoagulation are at risk for postoperative bleeding.
Lai, Wei; Lu, Shi-Chun; Li, Guan-Yin; Li, Chuan-Yun; Wu, Ju-Shan; Guo, Qing-Liang; Wang, Meng-Long; Li, Ning
AIM: To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion after splenectomy with gastroesophageal devascularization. METHODS: We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010. Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation, respectively. Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly. Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery, followed by oral warfarin and aspirin for one month regularly. The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50. Platelet and PT/INR were monitored. Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy. RESULTS: The patients’ data were collected and analyzed retrospectively. Among the patients, 94 developed early postoperative mural PSVT, including 63 patients in group A (63/153, 41.17%) and 31 patients in group B (31/148, 20.94%). There were 50 (32.67%) patients in group A and 27 (18.24%) in group B with mural PSVT in the main trunk of portal vein. After the administration of thrombolytic, anticoagulant and anti-aggregation therapy, complete or partial thrombus dissolution achieved in 50 (79.37%) in group A and 26 (83.87%) in group B. CONCLUSION: Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization, and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy. Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT. PMID:22807615
Anderson, D. R.; Fernandez, L. A.
Indications for using standard anticoagulants, heparin and warfarin; the dosage and route of administration; the importance of monitoring therapy with reliable laboratory indices; and complications of therapy are discussed. Acetylsalicylic acid and ticlopidine can be used as antiplatelet agents. Because their effect on platelet function is not monitored clinically, their clinical indications are emphasized. PMID:8495120
Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D
To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S
Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this
Odoom, J A; Sih, I L
One thousand lumbar epidural blocks in 950 patients undergoing vascular surgery are reported. All patients were receiving oral anticoagulants pre-operatively. Mean thrombotest (TT) was 19.3% (normal range 70-130%). During surgery intravascular heparin was administered. At the end of surgery, the kaolin cephalin clotting time (KCCT) was 68 (+/- 0.8) seconds (normal range 35-60 seconds), and partial thromboplastin time (PTT) was 536 (77.9%, normal control of 100%). Despite the anticoagulant therapy, no side effects were observed in any patient which could be related to haemorrhage or haematoma formation in the epidural space. It is concluded that, provided adequate precautions are taken, epidural analgesia can be safely used in patients receiving anticoagulant therapy.
Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin
A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Ullrich, Helen; Gori, Tommaso
Triple anticoagulant therapy is necessary in patients who are at increased risk for both arterial (in stent) and venous thrombosis, or have atrial fibrillation. Triple therapy however also poses a very high risk for bleeding events, particularly because this subset of patients is particularly frail due to the high incidence of comorbidities and advanced age. Very little randomized studies have tested the impact of the many possible combinations of anticoagulant/antiaggregant drugs, and surveys among practicing physicians show that the use of off-label therapies is very common. In a recent survey from our group, we observed that physicians are very divided in terms of what therapy should be recommended to patients with indication to anticoagulation and with a history of stenting. The use of novel anticoagulants was as frequent as that of vitamin K antagonists, and the duration of triple therapy was very variable.While these data probably show that decisions are usually taken on an individual basis, considering the patient's risk of ischemia and hemorrhagic events, much of this variability probably depends on the fact that, failing randomized trials, guidelines in this area are relatively less specific than in other ones.
van der Meer, F J; Rosendaal, F R; Vandenbroucke, J P; Briët, E
Insufficient data are available about the safety of oral anticoagulant therapy. The specialized organization of thrombosis services in the Netherlands can provide important information on the bleeding risk and various risk factors for bleeding in patients receiving oral anticoagulant therapy. In a follow-up study over a 12-month period beginning in January 1988 on all patients treated by the Leiden Thrombosis Service, the frequency of bleeding complications was assessed. A Poisson regression model was used to assess the relative contribution to the bleeding risk of age, sex, target zone (intensity of anticoagulant effect aimed at), achieved intensity of anticoagulant therapy (International Normalized Ratio), and the type of coumarin derivative used. Six thousand eight hundred fourteen patients experienced 1003 bleeding complications (16.5 per 100 treatment-years), 162 of which were major bleeds (2.7 per 100 treatment-years). Bleeding increased significantly with age (32% increase for all bleeding, 46% for major bleeding for every 10-year increase in age in comparison with age < 40 years). Women had more minor bleeding complications than men, whereas both sexes experienced major bleeding in an equal frequency. There was no influence of target zone, while every one-point increase in International Normalized Ratio gave 42% more major bleeding (54% more regarding all bleeding). Use of acenocoumarol resulted in fewer bleeds (26% less regarding all bleeding and 46% less regarding major bleeding) than use of phenprocoumon. The risk of anticoagulant therapy in a routine, real-life situation is similar as in the setting of several well-organized clinical trials. The risk of bleeding complications rises significantly with age and with the achieved intensity of anticoagulation, and is dependent on the type of coumarin derivative that is used.
Escolar, G; Diaz-Ricart, M; Arellano-Rodrigo, E
Activated coagulation factor X (FXa) is a common target for classic and newer anticoagulants. Parenteral anticoagulants with an indirect inhibitory action on FXa (low-molecular-weight heparins) have a well-established clinical efficacy in the prophylaxis and therapy of thromboembolic conditions. More recently developed direct oral anticoagulants (DOACs) have emerged as a new class of antithrombotic drugs. Rivaroxaban, apixaban and edoxaban are direct inhibitors of FXa approved for the management of venous thromboembolism and stroke prevention in atrial fibrillation. Although these DOACs are associated with fewer hemorrhagic side effects than classic vitamin K antagonists, bleeding is still a main complication. FXa antagonists had no specific agents that could reverse their antihemostatic effects. Andexanet alfa is a modified, recombinant human FXa molecule with an enhanced ability to bind to both direct and indirect FXa inhibitors, but unable to contribute to blood coagulation mechanisms. Andexanet alfa is designed to reverse the anticoagulant effects of FXa inhibitors. This review will address the preclinical pharmacology and the main aspects of the clinical development of andexanet alfa for the reversal of anticoagulant therapies with an inhibitory action on FXa. It will also summarize additional completed or ongoing studies on andexanet alfa available to the scientific community until present. Copyright 2017 Clarivate Analytics.
Doonquah, Ladi; Mitchell, Anika D
Minor oral surgical procedures make up a significant part of the daily practice of dentistry. With the increased sophistication of medical technology and medications there is increased likelihood of performing surgery on patients who are being treated for conditions that require some type of anticoagulant therapy. These patients are at an increased risk for perioperative bleeding or thrombotic complications if anticoagulation is discontinued or the dosage is adjusted. Therefore, a fine balance needs to be obtained and adequate preparation of these patients is the key to establishing this balance. This article reviews suggested approaches to the management of such patients.
Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations. PMID:27106121
Umemura, Y; Yamakawa, K; Ogura, H; Yuhara, H; Fujimi, S
ESSENTIALS: Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population. We conducted separate meta-analyses of anticoagulant therapy in three different populations. Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population. Further randomized controlled trials should focus on specific populations with septic DIC. Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC). We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis. We conducted separate meta-analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis-induced coagulopathy, and (iii) population with sepsis-induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all-cause mortality as the primary outcome and bleeding complications as the secondary outcome. We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis-induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62-0.85) in the population with sepsis-induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations
Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H
Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. © 2016 by The American Society of Hematology.
Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.
Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010
Tzoran, Inna; Brenner, Benjamin; Sakharov, Gleb; Trujillo-Santos, Javier; Lorenzo, Alicia; Madridano, Olga; López-Sáez, Juan Bosco; Monreal, Manuel
Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis. Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course. 1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p<0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p<0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p<0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate. Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Moia, Marco; Mantovani, Lorenzo Giovanni; Carpenedo, Monica; Scalone, Luciana; Monzini, Mara Silvia; Cesana, Giancarlo; Mannucci, Pier Mannuccio
New anticoagulant drugs alternative to vitamin K antagonists are currently under clinical evaluation. Patient's preferences should be considered in the development of new therapeutic strategies. Our study aim was to elicit patient preferences, and estimate their willingness to pay for the different treatment options. A Discrete Choice Experiment was administered to patients consecutively attending an anticoagulation clinic, either on stable oral anticoagulant therapy, or during their first visit at the time of starting therapy. Six treatment characteristics were analysed: route and number of medication administrations, frequency of monitoring, risk of some minor bleeding, the amount of attention required for drug/food interactions, requirement for dose adjustment, and out-of-pocket treatment cost. Relationships between patient's preferences and their characteristics were analysed. 255 patients participated (55 % men, with a mean age 64 years; 35.7 % on stable therapy). A statistically significant importance was attributed to all but two characteristics (the amount of attention required for interaction with other drugs/food and for dose adjustment.) Monthly patient willingness to pay was
Mellado, Meritxell; Pijoan, José I; Jiménez, David; Muriel, Alfonso; Aujesky, Drahomir; Bertoletti, Laurent; Decousus, Herve; Barrios, Deisy; Clará, Albert; Yusen, Roger D; Monreal, Manuel
The aim of this study was to assess the effectiveness of inferior vena cava (IVC) filter use among patients who develop recurrent symptomatic venous thromboembolism (VTE) on anticoagulant therapy. There is a lack of efficacy evidence of IVC filter therapy in patients with VTE recurrence on anticoagulant therapy. In this cohort study of patients with acute VTE identified from the RIETE (Registro Informatizado de la Enfermedad Tromboembólica) registry, the associations between IVC filter placement for VTE recurrence in the first 3 months of anticoagulant therapy and the outcomes of all-cause mortality, pulmonary embolism (PE)-related mortality, second recurrent VTE, and major bleeding rates through 30 days after diagnosis of recurrence were assessed. Among 17 patients treated with filters and 49 matched patients treated without filters for VTE recurrence that presented as deep vein thrombosis, propensity score-matched groups showed no significant differences in death for filter insertion compared with no insertion (17.7% vs. 12.2%; p = 0.56). Among 48 patients treated with filters and 91 matched patients treated without filters for VTE recurrence that presented as PE, propensity score-matched groups showed a significant decrease in all-cause death for filter insertion compared with no insertion (2.1% vs. 25.3%; p = 0.02). The PE-related mortality rate was not significantly lower for filter insertion than no insertion (2.1% vs. 17.6%; p = 0.08), though the point estimates markedly differed. Among patients with VTE recurrence during the first 3 months of anticoagulant therapy, IVC filter insertion was not associated with a survival benefit in patients who recurred with deep vein thrombosis, although it was associated with a lower risk for all-cause death in patients who recurred with PE. Copyright Â© 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Truong, Teresa; Armor, Becky L
Warfarin is considered a high-risk drug because of its narrow therapeutic window, variability in dose response, and multitude of drug and food interactions. Although travel advice is available for patients who are taking warfarin, it is geared toward patients who are traveling to developed countries and tends to be lacking in detail. We describe a 53-year-old woman with two mechanical heart valves and chronic atrial fibrillation who was taking warfarin for thromboembolism prophylaxis and had plans to travel to Vietnam for 10 weeks. Three days before her departure, she was prescribed amiodarone for long-term use. As a result of the extended duration of her travel and the complexities of warfarin use, the pharmacists who managed the patient's anticoagulation reviewed several aspects of a comprehensive management approach with the patient for a safe international trip. They assessed the patient's thromboembolic and hemorrhagic risks, and determined which other drugs (e.g., enoxaparin, phytonadione), dosages, and adequate supplies would be required along with warfarin, as well as how to safely transport these drugs during travel. In addition, the logistics of effectively monitoring international normalized ratio (INR) levels were evaluated, and methods of managing multiple potential scenarios were carefully planned out. Contact with the patient was made through pharmacist-directed telephone visits throughout the travel period. A total of 12 telephone visits were conducted with the patient during the 10 weeks of travel. Her INR was supratherapeutic on three occasions and was subtherapeutic once; however, neither enoxaparin nor phytonadione were needed during the travel period, and the patient returned safely to the United States. Effective and safe use of high-risk drugs for patients leaving the United States requires extensive pretravel planning, and pharmacists can play a central role in optimizing therapeutic outcomes for these patients during international travel.
Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam
This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.
Farge, Dominique; Trujillo-Santos, Javier; Debourdeau, Philippe; Bura-Riviere, Alessandra; Rodriguez-Beltrán, Eva Maria; Nieto, Jose Antonio; Peris, Maria Luisa; Zeltser, David; Mazzolai, Lucia; Hij, Adrian; Monreal, Manuel
Abstract In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8–6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3–7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2–12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID:26266353
Thompson, Ashley; Li, Fanny; Gross, A Kendall
Providing safe and high-quality care to critically ill patients receiving continuous renal replacement therapy (CRRT) includes adequate drug dosing and evaluation of patients' response to medications during therapy. Pharmacokinetic drug studies in acute kidney injury and CRRT are limited, considering the number of medications used in critical care. Therefore, it is important to understand the basic principles of drug clearance during CRRT by evaluating drug properties, CRRT modalities, and how they affect medication clearance. Few published studies have addressed drug disposition and clinical response during CRRT. Additionally, clotting in the CRRT circuit is a concern, so a few options for anticoagulation strategies are presented. This article reviews (1) the CRRT system and drug property factors that affect medication management, (2) the evidence available to guide drug dosing, and (3) anticoagulation strategies for critically ill patients receiving CRRT. ©2017 American Association of Critical-Care Nurses.
Moeinipour, Aliasghar; Zarifian, Ahmadreza; Sheikh Andalibi, Mohammad Sobhan; Shamloo, Alireza Sepehri; Ahmadabadi, Ali; Amouzeshi, Ahmad; Hoseinikhah, Hamid
It is common practice for patients with prosthetic cardiac devices, especially heart valve prosthesis, arterial stents, defibrillators, and pacemaker devices, to use anticoagulation treatment. When these patients suffer from multiple trauma after motor vehicle accidents, the best medical management for this challenging position is mandatory. This strategy should include a rapid diagnosis of all possible multiple organ injuries, with special attention to anticoagulation therapy so as to minimize the risk of thromboembolism complication in prosthetic devices. In this review, we describe the best medical management for patients with multiple trauma who use anticoagulants after heart valve replacement. We searched electronic databases PubMed/Medline, Scopus, Embase, and Google Scholar using the following terms: anticoagulant, warfarin, heparin, and multiple trauma. Also, similar studies suggested by the databases were included. Non-English articles were excluded from the review. For patients who use anticoagulation therapy, teamwork between cardiac surgeons, general surgeons, anesthesiologists, and cardiologists is essential. For optimal medical management, multiple consults between members of this team is mandatory for rapid diagnosis of all possible damaged organs, with special attention to the central nervous system, chest, and abdominal traumas. With this strategy, it is important to take note of anticoagulation drugs to minimize the risk of thromboembolism complications in cardiac devices. The best anticoagulant agents for emergency operations in patients with multiple trauma who are using an anticoagulant after heart valve replacement are fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC).
Pacemaker lead malpositioning may lead to severe clinical adverse events. Rarely, cases of inadvertent placement of a lead into the left ventricle are reported in the literature. We herein report a case of pacemaker lead malpositioning into the left ventricle via a persistent foramen ovale in a male caucasian patient. After this procedural adverse event, the patient suffered from two ischemic strokes despite antiplatelet and anticoagulation therapy. PMID:24650169
Blanco-Molina, Ángeles; Trujillo-Santos, Javier; Pesavento, Raffaele; Rosa, Vladimir; Falgá, Conxita; Tolosa, Carles; Mazzolai, Lucia; Sampériz, Ángel; Duce, Rita; Monreal, Manuel
Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors. © 2017 Elsevier Ltd. All rights reserved.
Vicente Barrero, Mario; Knezevic, Milan; Tapia Martín, Manuel; Viejo Llorente, Aurora; Orengo Valverde, Juan Carlos; García Jiménez, Francisco; López Pérez, Omar; Domínguez Sarmiento, Sergio; Díaz Cremades, Jose Manuel; Castellano Reyes, Juan
There is an evident need for procedural protocol for oral surgery patients who undergo oral anticoagulant treatment (OAT) because of: 1) the possible severity of complications and 2) the growing demand for OAT, which in some cases may be as much as 8% of the oral surgery patients that are referred to the hospital from primary care centers. In this study, the authors define the parameters for creating a proto- col applicable to this group of patients. The conclusion is that it is not necessary to suspend OAT before surgery; rather, these procedures should be performed under multidisciplinary medical control. The authors demonstrate that it is possible to perform oral surgery on OAT patients, without having to sus- pend treatment beforehand. A longitudinal study was performed in OAT patients that required some type of oral surgical procedures. After an INR control, the patient underwent surgery and afterwards the patient was given tranexamic acid as a mouth rinse. Postoperative hemorrhage was classified as slight when it lasted less than 5 minutes, moderate when it lasted longer than five minutes, and severe when it required blood transfusion. The study was performed over a 5-year period (1996-2000), by the maxillofacial surgery department. In that time period, 125 patients with OAT were treated; 90 of them were males and 35 were females. Tooth extraction was per- formed in 229 sessions and a total of 367 teeth were extracted, with an average of 1.6% per session. With regards to postoperative hemorrahage, it was slight in 210 cases (91.7%), moderate in 18 (7.9%) and severe only in one case (0.4%). All the variables were compared and no statistically significant differences were found. We believe that OAT should not be suspended before oral surgery, but it surgery should be performed under multidisciplinary control-especially in the case of the elderly (over 65) or with those patients that have other concomitant illnesses such as renal insufficiency or anemia or other
Shaha, Maya; Wüthrich, Erika; Stauffer, Yvonne; Herczeg, Franziska; Fattinger, Karin; Hirter, Kathrin; Papalini, Marianne; Herrmann, Luzia
This study aimed at developing and implementing evidence-based patient and family education on oral anticoagulation therapy. The number of persons with chronic diseases who live at home is increasing. They have to manage multiple diseases and complex treatments. One such treatment is oral anticoagulation therapy, a high risk variable dose medication. Adherence to oral anticoagulation therapy is jeopardised by limited information about the medications, their risk and complications, the impact of individual daily routine and the limited inclusion of family members in education. Hence, improved and tailored education is essential for patients and families to manage oral anticoagulation therapy at home. A community-based participatory research design combined with the Precede-Proceed model was used including a systematic literature review, posteducation analysis, an online nurse survey, a documentation analysis and patient/family interviews. The study was conducted between April 2010-December 2012 at a department of general internal medicine in a teaching hospital in Switzerland. Participants were the department's nursing and medical professionals including the patients and their families. The evidence-based patient and family education on oral anticoagulation therapy emerged comprising a learning assessment, teaching units, clarification of responsibilities of nurse professionals and documentation guidelines. The inclusion of the whole department has contributed to the development and implementation of this evidence-based patient family education on oral anticoagulation therapy, which encompasses local characteristics and patient preferences. This education is now being used throughout the department. © 2015 John Wiley & Sons Ltd.
Singh, Prabhat; Kalita, J.; Misra, U.K.
Background & objectives: There is paucity of studies on the quality of anticoagulation in neurological patients from India. This study evaluates the quality of oral anticoagulation therapy in neurology patients. Methods: Consecutive patients attending a tertiary care neurology service in north India who were prescribed oral anticoagulant (OAC), were included. Their international normalized ratio (INR) values were prospectively monitored and the earlier INR values of the patients who were already on OAC were retrospectively analyzed. The patients with multi-organ dysfunction, pregnancy and those below 18 yr of age were excluded. The therapeutic INR range was defined as per standard recommendations. The level of anticoagulation, factors interfering with OAC and complications were noted. Results: The results were based on 77 patients with median age 40 yr. Fifty one patients received OAC for secondary stroke prevention, 23 for cerebral venous sinus thrombosis (CVST) and three for deep vein thrombosis (DVT). A total 167.9 person-years of follow up was done with a median of 1.2 (0.3-9.3) years. Of the 1287 INR reports, 505 (39.3%) reports were in the therapeutic range, 496 (38.5%) were below and 282 (21.91%) were above the therapeutic level. Stable INR was obtained in 33 (42.86%) patients only. INR level was improved by dose adjustment in 20 (26%), drug modification in two (2.6%), and dietary adjustment in six (7.8%) patients. Three patients were sensitive and five were resistant to OAC. Complications were noted in 28 instances; thromboembolic in 16 and haemorrhagic stroke in 12. The overall complication rate was 16.7 per 100 person-years. Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR. PMID:27377498
Chopra, Sandeep; Kakkar, Naveen
Maintaining the international normalized ratio (INR) within the therapeutic range in patients on oral anticoagulant treatment is a challenge for the physician. Excessive anticoagulation poses the risk of bleeding in patients. Management strategies vary among clinicians although standard guidelines exist for the same. We conducted an audit in patients on oral anticoagulant therapy in our hospital with excessive anticoagulation. This retrospective study was carried out among patients on oral anticoagulant therapy for various thrombotic conditions with at least a single INR recording of 5 or more. Other than demographic details, the type of oral anticoagulant used, indication, duration of treatment, dosage and concomitant use of interacting drugs or alcohol were also recorded. Detail of the nature and site of bleed and management for the same was also noted. Data were analyzed using descriptive statistics. Fifty episodes with INR ≥ 5 (5.0-10.75) were noted in 44 patients (M:F = 1:1). Their age ranged from 20 to 88 years (mean 50.3 ± 16.4 years). The duration of anticoagulant therapy varied from 3 days to 180 months. Of the 43 episodes in patients who had no bleeding, the anticoagulant was stopped on 32 occasions for variable periods with dose reduction in the rest of the patients. Spontaneous bleeding was seen in seven patients (6 major and 1 minor). Among the seven patients with bleeding, other than stopping he oral anticoagulant drug, other measures taken were vitamin K therapy, fresh frozen plasma or packed red cell transfusion. Overall management strategy of patients with high INR was in compliance with standard recommendations.
Collins, R.; MacMahon, S.; Flather, M.; Baigent, C.; Remvig, L.; Mortensen, S.; Appleby, P.; Godwin, J.; Yusuf, S.; Peto, R.
OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer
Ho, L Y; Siu, C W; Yue, W S; Lau, C P; Lip, G Y; Tse, H F
Limited evidence is available on the safety and efficacy of anticoagulants in non-valvular atrial fibrillation (AF) patients with concomitant hypertension. We investigated the safety and efficacy of 476 consecutive anticoagulated Chinese outpatients with non-valvular AF and hypertension. Occurrence of ischaemic stroke and major bleeding, and international normalized ratio (INR) values during these events were recorded. There was no significant difference in anticoagulation control between patients with or without hypertension. INR-specific incidence rates of the events were calculated, which showed no excessive risk for ischaemic stroke (2.5 vs 1.6% per year, P=0.22) or major bleeding (3.9 vs 3.2% per year, P=0.29) in non-valvular AF patients with or without hypertension. In multivariate analysis, congestive heart failure, smoking and high CHADS2 score were independent predictors for ischaemic stroke, whereas use of antiplatelet agents was an independent predictor for bleeding. It can be noted that hypertension was not associated with ischaemic stroke or major bleeding. Hypertensive patients who achieved target blood pressure control (<130/80 mm Hg) had a lower ischaemic stroke (0.9 vs 3.1% per year, P=0.01), but similar bleeding risk compared with those not achieving target blood pressure. Our findings demonstrate the effects of hypertension on the outcomes of warfarin therapy; further investigation is needed to clarify whether more aggressive antihypertensive therapy could result in better outcomes in hypertensive patients with non-valvular AF.
Divchev, D; Nienaber, C; Ince, H
There is ongoing development of new therapeutic regimens in the use of antithrombotic agents and anticoagulants focussing on acute coronary syndrome (ACS) with an increasing impact on current guidelines over the last years. This was especially accompanied by an increase in innovative percutaneous coronary interventional (PCI) methods in patients with ACS, non-ST-segment elevation myocardial infarction (NSTEMI) or ST-segment elevation myocardial infarction (STEMI) with a need for therapeutics with more sufficient and effective antiplatelet action. On the other hand, newer direct and indirect thrombin inhibitors with primary use in prevention and therapy of thromboembolic events have been shown to have beneficial and even superior effects in ACS with or without PCI. The current review aims to report on the evidence-based use of approved antithrombotic agents and anticoagulants in ACS with special focus on PCI according to the actualized European guidelines.
Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety.
DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN
The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612
Iba, T; Gando, S; Thachil, J
The current management of disseminated intravascular coagulation (DIC) is based on aggressive treatment of the underlying condition and resuscitation with appropriate blood products. Anticoagulant therapy has appeared and disappeared in the different guidelines and important documents detailing the treatment of DIC. For example, Surviving Sepsis Campaign (SSC) guidelines, the 'global standard' for the management of severe sepsis, had recombinant activated protein C highly recommended in the original version, but this was withdrawn in the latest version due to the lack of evidence. In contrast, recent international guidance released from the International Society on Thrombosis and Haemostasis has introduced the potential efficacy of other agents. In sepsis-related DIC, the basis for anticoagulant therapy comes from the mounting evidence for the anti-inflammatory effects which these agents possess and can prove beneficial in septic situations. Several studies have clearly shown the important cross-talk between coagulation and inflammation in patients with sepsis. More recently, neutrophil extracellular traps and damage-associated molecular patterns (DAMPs), especially histones, have been demonstrated to play a crucial role in the coagulopathy of sepsis. Once again, the natural anticoagulants have an important function in neutralizing the effects of DAMPs and histones. In this review, in addition to examining the important role of anticoagulants in the septic milieu, the clinical studies examining antithrombin, recombinant thrombomodulin and plasma-derived activated protein C are detailed. However, large-scale randomized controlled trials are yet to be performed, with important consideration of the timing, dosage and duration of treatment. © 2014 International Society on Thrombosis and Haemostasis.
Rodriguez, Keila; Srivaths, Poyyapakkam R.; Tal, Leyat; Watson, Mary N; Riley, Alyssa A.; Himes, Ryan W.; Desai, Moreshwar S.; Braun, Michael C.
Pediatric liver failure patients frequently develop multiple organ failure and require continuous renal replacement therapy (CRRT) as part of supportive therapy in the pediatric intensive care unit. While many centers employ no anticoagulation for fear of bleeding complications, balanced coagulation disturbance predisposes these patients to clotting as well as bleeding, making maintenance of longer circuit life to deliver adequate dialysis clearance challenging. Regional citrate anticoagulation (RCA) is an attractive option as it avoids systemic anticoagulation, but since citrate metabolism is impaired in liver failure, concerns about toxicity has limited its use. Pediatric data on RCA with liver failure is very scarce. We aimed to establish safety and efficacy of RCA in pediatric liver failure patients on CRRT. Retrospective review of pediatric patients with liver failure receiving CRRT over 30 months. Demographic data and CRRT related data were collected by chart review. Citrate accumulation (CA) was defined as total calcium (mg/dl) /ionized calcium (mmol/L) ratio >2.5 for > 48 hours. Efficacy was assessed by filter life. Safety was assessed by frequency of adverse events ((AEs) defined as bleeding, hemodynamic instability, arrhythmias). Fifty-one patients (median age 3.5 (IQR 0.75–14.2) years) received 861 CRRT days; 70% experienced at least one episode of CA, only 37% were recorded as such in the medical record. AE rate was 93/1000 CRRT days and did not differ between CA days and others. Median filter life was 66 hours (IQR 29–74); 63% filters lasted longer than 48 hrs. Though common, CA was not associated with increased AEs on in pediatric liver failure patients on CRRT receiving RCA. Filter life was adequate. RCA appears an effective anticoagulation for CRRT in pediatric liver failure. Application of a structured definition would increase recognition of CA to allow timely intervention. PMID:28792509
Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel
Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483
LaVallee, Jeffrey; Royer, Regan; Smith, Geoffrey
Patients on anticoagulation or antiplatelet therapy may be at higher risk for bleeding complications following intramuscular chemodenervation injections. Musculoskeletal ultrasound may be able to reduce the risk of bleeding complications by providing real-time visualization of vascular structures and postinjection monitoring. Limited data exist addressing the risk of bleeding complications following ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures in the setting of anticoagulation or antiplatelet therapy. To provide initial outcome data regarding bleeding complications in patients on anticoagulation or antiplatelet therapy who have received ultrasound-guided botulinum neurotoxin intramuscular chemodenervation procedures. Retrospective, medical record review. Academic institution outpatient spasticity clinic. Total of 328 ultrasound-guided intramuscular botulinum toxin injections performed in 15 patients (mean age 53.8 years) with the predominant indication for chemodenervation being spastic paresis secondary to stroke. The medical records of all patients receiving ultrasound-guided intramuscular chemodenervation procedures performed between July 1, 2011, and October 16, 2015, were reviewed for demographic information, details regarding anticoagulation therapy, procedure specifics, and postinjection bleeding complications. All patients had a postinjection ultrasound to screen for hematoma. Prevalence of clinically significant bleeding complications and of sonographically documented subclinical bleeding complications following ultrasound-guided chemodenervation procedures in patients on anticoagulation or antiplatelet therapy. Of 328 procedures, only 2 subclinical hematomas were detected, resulting in a bleeding complication rate of 0.61% in this patient population. The target muscles in these cases were tibialis posterior and pronator teres, and both cases were in patients on anticoagulation therapy (as opposed to antiplatelet
Armstrong, Melissa J; Schneck, Michael J; Biller, José
Growing evidence suggests that perioperative withdrawal of ASA for secondary stroke prevention increases thromboembolic risk without the associated benefit of decreased bleeding complications. ASA maintenance is acceptable in many procedures, including invasive ones. Many procedures, in particular ophthalmologic, dermatologic, and dental surgeries, also are safe while continuing oral AC. Warfarin has been continued successfully even in some surgeries that have high bleeding risk. When the risk is too high, temporary bridging therapy with LWMH is safe in many populations. Although the exact thromboembolic risks associated with temporary cessation of AP and AC are unknown and likely low, morbidity and mortality associated with thromboembolism are high. Further studies investigating the risks and benefits of maintaining AP and AC during procedures, particularly invasive ones, are needed. Meanwhile, it is critical that physicians understand the risks and benefits of perioperative AP and AC and the variety of procedures in which these agents can be safely continued.
ten Berg, J M; Hutten, B A; Kelder, J C; Verheugt, F W; Plokker, H W
In the randomized Balloon Angioplasty and Anticoagulation Study (BAAS), the addition of oral anticoagulants to aspirin significantly reduced early and late events after coronary angioplasty. However, bleeding episodes were increased. The present report studied the intensity and the duration of anticoagulation as predictors of thrombotic and bleeding events. A total of 530 patients, 34% of whom received a stent, were treated with aspirin plus coumarins. Half of the patients were randomized to angiographic follow-up. The target international normalized ratio (INR) was 2.1 to 4.8 during angioplasty and 6-month follow-up. Thrombotic events were death, myocardial infarction, target lesion revascularization, and thrombotic stroke. Bleeding complications were hemorrhagic stroke, major extracranial bleeding, and false aneurysm. "Optimal" anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. There were 17 early thrombotic events (3.2%), 7 early bleeding episodes (1.3%), and 10 false aneurysms (1.9%). The incidence rate for both early thrombotic and bleeding events was lowest in patients in the target range. A total of 61 late thrombotic events occurred (11.6%). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19 to 0.57) and was associated with a 0.21 mm (95% CI, 0.17 to 0.42) larger vessel lumen at 6 months. Late bleeding episodes (1.4%) were lowest in patients in the target range. Coumarins started before coronary angioplasty with a target INR of 2.1 to 4.8 led to the lowest procedural event rate, without an increase in bleeding episodes. During follow-up, optimal anticoagulation was associated with a decrease in the incidence of late events by 67% and a significant improvement in 6-month angiographic outcome.
Degirmenci, S-E; Steib, A
Peri-operative management of the risks of hemorrhage and thrombosis related to gastrointestinal surgery tailored to patient characteristics are part of daily multidisciplinary practice tasks. The goal of this update is to discuss current practices concerning antithrombosis prophylaxis and the management of recently developed anticoagulants and antiplatelet agents. The duration of prophylaxis is 1 month for oncological surgery. The recommended doses in bariatric surgery are twice daily injections of low-molecular weight heparin without exceeding a total dose of 10,000 IU/day. Dual antiplatelet therapy is necessary for 6 weeks after placement of bare-metal stents, from 6-12 months for drug-eluting stents, and 12 months after an acute coronary artery syndrome. Abrupt discontinuation of antiplatelet therapy exposes the patient to an increased risk of thrombosis. Data are insufficient to make specific recommendations for antiplatelet therapy in gastrointestinal surgery. For major digestive surgery, prescription of daily aspirin should be discussed case by case. If discontinuation of treatment is absolutely necessary, this should be as short as possible (aspirin: 3 days, ticagrelor and clopidogrel: 5 days, prasugrel: 7 days). The modalities for elective management of new oral anticoagulants are similar to those for classical vitamin K antagonists (VKA) therapy, except that any overlapping with heparin administration must be avoided. In the emergency setting, an algorithm can be proposed depending on the drug, the available coagulation tests and the interval before performing surgery.
Mook-Kanamori, Barry B.; Fritz, Daan; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik
Objective To study the incidence, clinical presentation and outcome of intracranial hemorrhagic complications in adult patients with community associated bacterial meningitis. Methods Nationwide prospective cohort study from all hospitals in the Netherlands, from 1 March 2006, through 31 December 2010. Results Of the 860 episodes of bacterial meningitis that were included, 24 were diagnosed with intracranial hemorrhagic complications: 8 upon presentation and 16 during clinical course. Clinical presentation between patients with or without intracranial hemorrhage was similar. Causative bacteria were Streptococcus pneumoniae in 16 patients (67%), Staphylococcus aureus in 5 (21%), Pseudomonas aeruginosa and Listeria monocytogenes both in 1 patient (4%). Occurrence of intracranial hemorrhage was associated with death (63% vs. 15%, P<0.001) and unfavorable outcome (94% vs. 34%, P<0.001). The use of anticoagulants on admission was associated with a higher incidence of intracranial hemorrhages (odds ratio 5.84, 95% confidence interval 2.17–15.76). Conclusion Intracranial hemorrhage is a rare but devastating complication in patients with community-associated bacterial meningitis. Since anticoagulant therapy use is associated with increased risk for intracranial hemorrhage, physicians may consider reversing or temporarily discontinuing anticoagulation in patients with bacterial meningitis. PMID:23028898
Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate. PMID:21345279
Haibo, Zhang; Jinzhong, Li; Yan, Liu; Xu, Meng
The purpose of this study was to define the optimal international normalized ratio (INR) intensity of oral anticoagulant therapy in Chinese patients with valve replacement surgery. We studied 1,658 patients who underwent mechanical valve replacement in Beijing Anzhen Hospital; the focus of the study was on correlation between intensity of anticoagulant therapy and thromboembolism/hemorrhage complications. We further followed up 1,508 patients for 46 ± 16 months (range 1-61 months). Average INR was 2.13 ± 0.56, and warfarin dose was 3.09 ± 0.85 mg/day. The incidence rate of anticoagulation-related thromboembolism was 1.17 per 100 patient-years (%/pt-y), and the incidence rate of anticoagulation-related hemorrhage was 2.02%/pt-y. The incidence rate of total complications (i.e., combined thromboembolism and hemorrhages) was 3.24%/pt-y. The rate of total complications in group on INR 1.3-2.3 (aortic valve replacement: 1.3-1.8; mitral valve replacement and double valve replacement: 1.8-2.3) was the lowest among all anticoagulant therapy regimens followed. In conclusion, the relatively low anticoagulant strategy presented above efficiently prevents thrombosis and hemorrhage complications.
Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu
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.
Madridano, Olga; del Toro, Jorge; Lorenzo, Alicia; Martín, Mar; Gómez Cerezo, Jorge; Hernández, Luis; Prandoni, Paolo; Monreal, Manuel
Patients with acute venous thromboembolism (VTE) are at increased risk for the development of subsequent arterial ischemic events unrelated to the diagnosis of VTE. Accurate identification of VTE patients at increased risk for ischemic events during the course of anticoagulation may help to select those who would potentially benefit from concomitant therapy with anticoagulants and antiplatelets. We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry to assess the rate and severity of subsequent ischemic events (ie, stroke, myocardial infarction, lower limb amputation, or mesenteric ischemia) appearing during the course of anticoagulant therapy and tried to identify risk factors for these events. From February 2009 to March 2014, 23,370 patients were recruited: 12,397 initially presenting with pulmonary embolism (PE) and 10,973 with deep venous thrombosis. During the course of anticoagulation (mean, 9.2 months), 597 patients developed recurrent VTE, 652 bled, 162 had ischemic events (stroke, 86; myocardial infarction, 53; limb amputation, 13; mesenteric ischemia, 11), and 2063 died. Of these, 29 patients died of recurrent PE, 83 of bleeding, and 53 of the ischemic events. On multivariable analysis, cancer (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.21-2.61), chronic lung disease (HR, 1.54; 95% CI, 1.05-2.26), renal insufficiency (HR, 1.72; 95% CI, 1.25-2.36), anemia (HR, 1.54; 95% CI, 1.11-2.14), prior artery disease (HR, 1.84; 95% CI, 1.29-2.64), and diabetes (HR, 1.58; 95% CI, 1.10-2.27) independently predicted the risk for ischemic events. Most of these variables also predicted major bleeding (cancer, chronic lung disease, renal insufficiency, anemia, and prior artery disease) or recurrent PE (cancer, chronic lung disease, anemia, and prior artery disease). In patients receiving anticoagulation for VTE, the mortality due to PE recurrences was lower than the mortality due to ischemic events. Most independent predictors for
Davis, Estella M; Packard, Kathleen A; Knezevich, Jon T; Campbell, Jennifer A
Abstract Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low-molecular-weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin-bound thrombin, risk of heparin-induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmaco-dynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high-risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin
Virdee, Mandeep S; Stewart, Derek
Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA2DS2-VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA2DS2-VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA2DS2-VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA2DS2-VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re
Maeda, Koichiro; Koga, Masatoshi; Okada, Yasushi; Kimura, Kazumi; Yamagami, Hiroshi; Okuda, Satoshi; Hasegawa, Yasuhiro; Shiokawa, Yoshiaki; Furui, Eisuke; Nakagawara, Jyoji; Kario, Kazuomi; Nezu, Tomohisa; Minematsu, Kazuo; Toyoda, Kazunori
A nationwide survey was conducted regarding anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular atrial fibrillation (NVAF). A questionnaire on standard therapeutic strategy for warfarin-related ICH in patients with NVAF was mailed to 416 institutes. A total of 329 physicians (79%) responded with a completed questionnaire. On admission, all respondents stopped warfarin medication and 94% normalized the international normalized ratio (INR) mainly by Vitamin K (63%), followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%). Afterwards, 91% of the respondents restarted anticoagulation and 3% used antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed with restarting antithrombotic therapy. As contraindications for resuming anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were often chosen. Of those who restarted anticoagulation, the timing was within 4 days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29 days or later in 18%. The major key finding on follow-up CT to restart anticoagulation was the absorption tendency of hematomas (47%). When restarting anticoagulation, 76% of the respondents used warfarin alone and 20% used either unfractionated heparin plus warfarin or heparin alone. A large majority of respondents responsible for ICH management stopped oral warfarin medication and normalized INR on admission, and restarted anticoagulation after acute ICH in patients with NVAF. However, the strategies to normalize INR and to restart anticoagulant therapy varied greatly and depended on each individual physician's decision. Copyright © 2011 Elsevier B.V. All rights reserved.
Mutlu, Ilknur; Mutlu, Mehmet Firat; Biri, Aydan; Bulut, Berk; Erdem, Mehmet; Erdem, Ahmet
This study investigates the effects of anticoagulant therapy on pregnancy outcomes in 204 patients with thrombophilia and previous poor obstetric outcomes. Patients with poor obstetric history (pre-eclampsia, intrauterine growth retardation, fetal death, placental abruption, recurrent pregnancy loss) and having hereditary thrombophilia were included in this study. Poor obstetric outcomes were observed more frequently in patients who had not taken anticogulant therapy compared with treated group. Live birth rate, gestational age at birth and Apgar scores were significantly higher in the treated group when compared with the untreated group. There were no significant differences in terms of birthweight, mode of delivery and admission rates to the neonatal intensive care unit (NICU). Low-molecular-weight heparin (LMWH) plus acetylsalicylic acid (ASA) had higher gestational age at birth, Apgar scores, live birth rate and a lower abortion rates when compared with controls; in contrast, no significant difference was observed in terms of birthweight, mode of delivery, obstetric complications and admission rates to NICU. There were no significant differences between control group and both LMWH only and ASA only groups in terms of gestational age at birth, Apgar scores, birthweight, mode of delivery, obstetric complications and admission rates to NICU. Only LMWH group had higher live birth rate as compared with control group. The use of only ASA did not seem to affect the perinatal complication rates and outcomes. In conclusion, anticoagulant therapy with both LMWH and ASA seems to provide better obstetric outcomes in pregnant women with thrombophilia and previous poor obstetric outcomes.
You, Joyce H S
The decision as to whether to use more expensive novel oral anticoagulants (NOACs) or invest resources for quality improvement of warfarin therapy requires input from both clinical and economic analyses. Cost-effectiveness of NOACs compared to warfarin therapy at various levels of patient-time in therapeutic range (TTR) in patients with atrial fibrillation was examined, from the healthcare provider's perspective. A Markov model was used to compare life-long economic and treatment outcomes of warfarin and NOACs in a hypothetical cohort of 65-year-old atrial fibrillation patients with CHADS2 scores of 2 or above. Model inputs were derived from clinical trials published in the literature. The outcome measure was incremental cost per quality-adjusted life-year (QALY) gained (ICER). Using United States Dollar (USD) 50,000 as the threshold of willingness-to-pay per QALY, NOACs therapy was cost-effective when TTR of warfarin therapy was 60 % or below, or monthly cost of warfarin management increased by two-fold or more to achieve 70 % TTR. Warfarin therapy was cost-effective when TTR of warfarin was 70 % with up to a 1.5-fold increment in monthly cost of care, or when TTR reached 75 % with monthly cost of warfarin care increased up to three-fold. At TTR 60 %, 70 % and 75 %, NOACs was cost-effective when monthly drug cost was < USD 200, < USD 122-185 and < USD 85-145, respectively. 10,000 Monte Carlo simulations showed NOACs to be cost-effective 83.6 %, 50.7 % and 32.7 % of the time at TTR of 60 %, 70 % and 75 %, respectively. The acceptance of NOACs as cost-effective was highly dependent upon drug cost, anticoagulation control for warfarin, and anticoagulation service cost.
Angiolillo, Dominick J; Ferreiro, José Luis
Coronary atherothrombotic disease, including chronic stable angina and acute coronary syndromes (ACS), is associated with significant global burden. The acute clinical manifestations of atherothrombotic disease are mediated by occlusive arterial thrombi that impair tissue perfusion and are composed of a core of aggregated platelets, generated by platelet activation, and a superimposed fibrin mesh produced by the coagulation cascade. Long-term antithrombotic therapies, namely oral antiplatelet agents and anticoagulants, have demonstrated variable clinical effects. Aspirin and P2Y12 adenosine diphosphate (ADP) receptor antagonists have been shown to reduce the risk for thrombosis and ischaemic events by blocking the thromboxane (Tx) A2 and platelet P2Y12 activation pathways, respectively, whereas the benefits of oral anticoagulants have not been consistently documented. However, even in the presence of aspirin and a P2Y12 receptor antagonist, the risk for ischaemic events remains substantial because platelet activation continues via pathways independent of TxA2 and ADP, most notably the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antithrombotic therapies include those targeting the platelet, such as the new P2Y12 antagonists and a novel class of oral PAR-1 antagonists, and those inhibiting the coagulation cascade, such as the new direct factor Xa antagonists, the direct thrombin inhibitors, and a novel class of factor IX inhibitors. The role of emerging antiplatelet agents and anticoagulants in the long-term management of patients with atherothrombotic disease will be determined by the balance of efficacy and safety in large ongoing clinical trials.
Cantin, Ariane; Lahaie, Alexandre; Odobasic, Bojan; Tremblay, Marie-Philip; Wazzan, Dana; Caron, Stéphanie; Leblanc, Caroline; Martineau, Josée; Lalonde, Lyne
The ACO Program (Programme ACO), a continuous quality improvement program (CQIP) in anticoagulation therapy, was offered in community pharmacies as a pilot project. To evaluate the participants' appreciation for the various activities of the program. Participants had access to training activities, including an audit with feedback, online training activities (OTA), clinical tools and support from facilitators. Cognitive behavioural learning determinants were evaluated before and 5 months after the beginning of the program. Participants' satisfaction and perception were documented via online questionnaires and a semistructured interview. Of the 52 pharmacists in the ACO Program, 47 participated in this evaluation. Seventy-seven percent of the participants completed at least 1 OTA and 6% published on the forum. The feeling of personal effectiveness rose from 8.01 (7.67-8.35) to 8.62 (8.24-8.99). The audit and feedback, as well as the high-quality OTA and their lecturers, were the most appreciated elements. There was a high OTA participation rate. The facilitators seemed to play a key role in the CQIP. The low level of participation in the forum reflects the known phenomenon of social loafing. Technical difficulties affecting the platform and data collection for the audit with feedback constituted limitations. The CQIP in anticoagulation therapy is appreciated by community pharmacists and is associated with an improved feeling of personal effectiveness.
Brodowska-Kania, Dorota; Niemczyk, Stanisław
Oral anticoagulant (OAC) therapy in haemodialysis patients causes a great deal of controversy. This is because a number of pro- and anticoagulant factors play an important role in end-stage renal failure due to the nature of the disease itself. In these conditions, the pharmacokinetic and pharmacodynamic properties of the OACs used change as well. In the case of the treatment of venous thromboembolism, the only remaining option is OAC treatment according to regimens used for the general population. Prevention of HD vascular access thrombosis with the use of OACs is not very effective and can be dangerous. However, OAC treatment in patients with atrial fibrillation in dialysis population may be associated with an increase in the incidence of stroke and mortality. Doubts should be dispelled by prospective, randomised studies; at the moment, there is no justification for routine use of OACs in the above-mentioned indications. In selected cases of OAC therapy in this group of patients, it is absolutely necessary to control and monitor the applied treatment thoroughly. Indications for the use of OACs in patients with end-stage renal disease, including haemodialysis patients, should be currently limited. PMID:24379737
Kobalava, Zh D; Villewalde, S V; Troitskaya, E A
Suboptimal medication adherence to anticoagulation therapy is a widespread problem and is associated with increases in risk of thromboembolic or haemorrhagic events. Standard therapy with warfarin is associated with suboptimal adherence due to narrow therapeutic window, frequent side effects and need for INR control. Much shorter half-life of NOACs raises the question of optimal dosing regimen. Higher efficacy and safety of twice-daily dosing regimen of NOACs is based on the results of pharmacokinetic models, data from phase 2 and phase 3 trials and metanalysis of 4 phase 3 trials. Twice-daily dosing regimen of apixaban reflects the priority of clinical outcomes. AVERROES, ARISTOTLE and AMPLIFY trials provide strong evidence of efficacy and safety of twice-daily dosing regimen of apixaban. First results of AEGEAN-trial have shown high adherence and persistence to apixaban.
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
Butticè, Salvatore; Macchione, Luciano; Netsch, Christopher; Tanidir, Yiloren; Dragos, Laurian; Pappalardo, Rosa; Magno, Carlo
Purpose Thulium vaporesection of the prostate (ThuVARP) is a new and safe approach for patients receiving anticoagulant therapy in whom transurethral resection of the prostate (TURP) may possess a high bleeding risk. We aimed to demonstrate the efficacy and safety of ThuVARP in patients receiving oral antiplatelet/anticoagulant (OAP/OAC) therapy. Materials and Methods A total of 103 patients who underwent ThuVARP between 2011 and 2013 were enrolled in the study. Patients were divided into 2 groups. Group A consisted of 47 patients who underwent low molecular weight heparin (LMWH) bridging and group B consisted of 56 patients who were operated on while receiving OAP/OAC therapy. Results The drop in hemoglobin levels in the pre- and postoperative periods was significantly higher in group A than in group B. When subgroups were analyzed, the mean drop in hemoglobin was significantly lower in the warfarin and ticlopidine subgroups of group B than in group A. International Prostate Symptom Scores were significantly lower 3, 12, 18, and 24 months after surgery in group A than in group B. Quality of life scores, maximal flow rate values, and postmicturition residual urine volumes (mL) were similar between the 2 groups. A total of 38 and 41 patients in groups A and B, respectively, had no complications. Conclusions Our study showed the safety profile of continuing different OAP/OAC therapies in terms of bleeding problems in patients undergoing ThuVARP. We strongly recommend abandoning LMWH bridging and maintaining the OAP/OAC regimen patients are already receiving. PMID:28480345
Paparella, Domenico; Di Mauro, Michele; Bitton Worms, Keren; Bolotin, Gil; Russo, Claudio; Trunfio, Salvatore; Scrofani, Roberto; Antona, Carlo; Actis Dato, Guglielmo; Casabona, Riccardo; Colli, Andrea; Gerosa, Gino; Renzulli, Attilio; Serraino, Filiberto; Scrascia, Giuseppe; Zaccaria, Salvatore; De Bonis, Michele; Taramasso, Maurizio; Delgado, Luis; Tritto, Francesco; Marmo, Joseph; Parolari, Alessandro; Myaseodova, Veronika; Villa, Emmanuel; Troise, Giovanni; Nicolini, Francesco; Gherli, Tiziano; Whitlock, Richard; Conte, Manuela; Barili, Fabio; Gelsomino, Sandro; Lorusso, Roberto; Sciatti, Edoardo; Marinelli, Daniele; Di Giammarco, Gabriele; Calafiore, Antonio Maria; Sheikh, Azmat; Alfonso, Juan Jaime; Glauber, Mattia; Miceli, Antonio
To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 ± 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six-month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Yang, Liyong; Zhao, Hongyou
Photodynamic Therapy (PDT) is one of the tumor-targeting therapeutics, and has been an established medical practice in recent years. PDT mediates tumor destruction mainly by killing tumor cells directly and damaging the tumor-associated vasculature, also inducing an immune response against tumor cells. For the Photofrin-mediated PDT, Vascular system injury is the predominant destruction that results in vascular collapse and blood plasma leakage, then leading to tumor infarction. However, thrombus formation during PDT may influence the light transmission and oxygen supply. Also some tumor cells not killed by PDT may irritate angiogenesis, causing the tumor recurrence under the condition of hypoxia after PDT. In our work, to prolong coagulation and formation of thrombus, an anticoagulant heparin was employed before the Photofrin-mediated PDT. After being administrated both Photofrin and anticoagulant heparin, the BALB/c mice with the subcutaneous EMT6 mammary carcinomas model were exposed to laser (635nm). And then an enhanced effect was received. Our experiments indicated that its antitumor effect may be attributed to the improvement of the light delivery to the deep part of tumor and oxygen supply for PDT. The results suggested that heparin can be used to enhance the effect of PDT in a solid tumor treatment.
Cromme, L; Völler, H; Gäbler, F; Salzwedel, A; Taborski, U
Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.
Stjepanović, Mihailo; Buha, Ivana; Raljević, Snezana; Babić, Uroš; Savić, Milan; Mašković, Jovana; Roksandić, Marina; Marić, Dragana
Retroperitoneal hematoma may occur as a result of trauma, but also from rapture of arterial aneurysms (aortic or iliac), surgical complications, tumors or anticoagulation therapy. We presented a patient on permanent anticoagulation therapy. On the day of admission to our institudon, the patient had the value of his INR 5.57 which required immediate suspension of the therapy. The main symptom in this patient was pain in the right inguinal canal with propagation along the right leg, which was indicated in clinical picture of spontaneous retroperitoneal haematoma. After three days the fall of hemoglobin occurred, so the additonal diagnostics was done. A computed tomography of the abdomen was performed showing well limited, large retroperitoneal hematoma (213 x 79 x 91 mm). Transfusion of concentrated red blood cells was performed twice with satisfactory correction of hemoglobin level, and four units of fresh frozen plasma. The patient was hemodynamically stabilized and discharged after a two-month long intensive care unit treatment, with the advice to use low-molecular weight heparin 2 x 0.4 mg subcutaneusly, due to persistent arrhythmia. In patients on anticoagulation therapy regular monitoring of the anticoagulant status is extremely important, because of the possibility of fatal complications development, such as retroperitoneal hematoma.
Avellana, Patricia; Segovia, Javier; Ferrero, Andreu; Vázquez, Rafael; Brugada, Josep; Borrás, Xavier; Alonso-Pulpón, Luis; Cinca, Juan
In patients with heart failure, left ventricular ejection fraction ≤35% and sinus rhythm without conditions such as atrial fibrillation, thrombus or history of thromboembolic events, the use of anticoagulation is controversial. Our objective was to evaluate the anticoagulation strategy in these patients, variables associated with its use, and its effects on various cardiovascular events. Of the patients included in the REDINSCOR registry with left ventricular ejection fraction ≤35% and sinus rhythm without other anticoagulation indications (including patients with heart failure from 19 Spanish centres), we compared those who received this treatment with the remaining patients. Between 2007 and 2010, 2263 patients were included, of whom 902 had left ventricular ejection fraction ≤35% and sinus rhythm. Of these, 237 (26%) were receiving anticoagulation therapy. Variables associated with this treatment were a lower left ventricular ejection fraction, ischemic etiology, advanced functional class, wider QRS, larger left atrial diameter, and hospitalization. After 21(11-32) months of median follow-up, there were no significant differences in total mortality (14% versus 12.5%) or stroke (0.8% versus 0.9%). A propensity score adjusted multivariate analysis showed a reduction in a combined end-point including cardiac death, heart transplantation, coronary revascularization, and cardiovascular hospitalization (hazard ratio: 0.74; 95% confidence interval, 0.56-0.97; P=.03) in patients receiving anticoagulation therapy. No information regarding bleeding was collected in the follow-up. In a large and contemporary series of patients with heart failure, left ventricular ejection fraction ≤35% and sinus rhythm, 26% received anticoagulation therapy. This was not associated with lower mortality or stroke incidence, although there was a reduction in major cardiac events. Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.
Holmgren, K; Andersson, G; Fagrell, B; Johnsson, H; Ljungberg, B; Nilsson, E; Wilhelmsson, S; Zetterquist, S
The length of time for which deep vein thrombosis (DVT) should be treated with oral anticoagulants (OA) is controversial. In this study, 135 patients with symptomatic first period DVT (83% with proximal DVT) were randomly allocated to OA for one or six months. The diagnosis of initial and recurrent DVT was confirmed by phlebography or plethysmography and thermography, or by a combination of all these methods. Pulmonary emboli were confirmed by lung scans or at autopsy. The patients were followed for at least one year. One patient had to discontinue OA prematurely because of haemorrhage. Seventeen patients left the project for other reasons, ten during and seven after therapy; in one of these DVT recurred. The recurrence rate during the first year was high (17% symptomatic recurrences) irrespective of whether OA had been given for one or six months.
Inchingolo, Francesco; Tatullo, Marco; Abenavoli, Fabio M; Marrelli, Massimo; Inchingolo, Alessio D; Scacco, Salvatore; Papa, Francesco; Inchingolo, Angelo M; Dipalma, Gianna
Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Among the 193 patients, only 2 had postoperative complications. We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients.
Introduction Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. Materials and methods A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Results Among the 193 patients, only 2 had postoperative complications. Conclusions We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients. PMID:21771331
Kabłak-Ziembicka, Anna; Bryniarski, Krzysztof; Wrotniak, Leszek; Ostrowska-Kaim, Elżbieta; Żmudka, Krzysztof; Przewłocki, Tadeusz
Introduction Triple anticoagulation therapy (TT), comprising dual antiplatelet therapy (DAPT) and oral anticoagulation (OAC), is essential in atrial fibrillation (AF) patients after percutaneous coronary intervention (PCI), but it increases the bleeding risk. Aim To assess TT models, in- and out-hospital bleeding and thromboembolic complications, and TT alterations. Material and methods During 12 months, consecutive AF post-PCI patients were scheduled for TT. Alterations in TT and thromboembolic events (death, myocardial infarction, ischemic stroke, in-stent thrombosis, peripheral embolization) were recorded. Major, non-major and minor bleeding episodes were assessed. Results One hundred and thirty-six out of 3171 patients, aged 73.0 ±8.4 years (90 male), were included. Intra-hospitally, thrombotic events occurred in 9 (6.6%), while bleeding events occurred in 71 (52.2%) patients. Access-site hematoma and blood transfusions during in-hospital stay predisposed physicians to heparin administration as part of TT on discharge (p = 0.018 and p = 0.033 respectively). Eventually, DAPT plus warfarin or plus novel oral anticoagulant (NOAC) or plus low molecular weight heparin was prescribed in 72 (52.9%), 53 (39%), and 11 (8.1%) patients, respectively. HAS-BLED and CHA2DS2-VASc scores were similar between subgroups (p = 0.63 and p = 0.64 respectively). During 10.2 ±4.2 months of follow-up, 11 (8.1%) deaths, and 9 (6.6%) non-fatal thromboembolic events occurred. Bleeding events occurred in 45 (34.6%) patients, including 14 (10.3%) major. TT was the only factor associated with increased risk of major bleeding (18.6% vs. 4.2%, p = 0.008). Early termination of any TT component, which concerned 59 (45.4%) patients, did not increase the risk of thromboembolic events (p = 0.89). Conclusions Our study indicates that TT is associated with high mortality and bleeding rates in a relatively short period of time. Discontinuation of any TT drug did not increase the thromboembolic event
Although anticoagulation therapy is the primary treatment for deep vein thrombosis (DVT), it has not been associated with the rapid recanalization of the venous occlusion. Moreover, it is associated with long-term disability due to post-thrombotic syndrome (PTS). In contrast, pharmacomechanical endovascular intervention (PMI) results in more rapid clinical improvement in DVT patients, but there are few reports on its long-term outcomes. This retrospective study evaluated the clinical effectiveness of PMI compared to conventional anticoagulation therapy (ACA) for acute and subacute iliofemoral DVT. We reviewed the medical records of 102 patients with iliofemoral DVT. A total of 46 patients for ACA and 56 patients for PMI were enrolled. We analyzed the clinical differences between the PMI and ACA groups by comparing the clinical signs, residual DVT free-rate, and PTS-free rate. There were no statistically significant differences in the demographic characteristics and risk factors except age between the groups (age: ACA, 52.0 ± 18.0 years; PMI, 59.0 ± 17.0 years; P = 0.035). The 1-, 3-, and 5-year residual DVT-free rate (ACA = 84.7%, 71.6%, and 46.0%; PMI = 82.1%, 76.8%, and 76.8%, respectively; P = 0.235) was not significantly different. However, the 1-, 3-, and 5-year PTS-free rate was significantly different (ACA = 93.5%, 74.0%, and 55.7%; PMI = 92.9%, 90.0%, and 90.0%, respectively; P = 0.019). There was no significant difference in the rate of other complications. PMI showed a lower incidence of PTS during the follow-up period. Therefore, PMI should be considered as an effective therapeutic modality for patients with iliofemoral DVT. PMID:27914131
Kim, In Sub; Jo, Won Min
Although anticoagulation therapy is the primary treatment for deep vein thrombosis (DVT), it has not been associated with the rapid recanalization of the venous occlusion. Moreover, it is associated with long-term disability due to post-thrombotic syndrome (PTS). In contrast, pharmacomechanical endovascular intervention (PMI) results in more rapid clinical improvement in DVT patients, but there are few reports on its long-term outcomes. This retrospective study evaluated the clinical effectiveness of PMI compared to conventional anticoagulation therapy (ACA) for acute and subacute iliofemoral DVT. We reviewed the medical records of 102 patients with iliofemoral DVT. A total of 46 patients for ACA and 56 patients for PMI were enrolled. We analyzed the clinical differences between the PMI and ACA groups by comparing the clinical signs, residual DVT free-rate, and PTS-free rate. There were no statistically significant differences in the demographic characteristics and risk factors except age between the groups (age: ACA, 52.0 ± 18.0 years; PMI, 59.0 ± 17.0 years; P = 0.035). The 1-, 3-, and 5-year residual DVT-free rate (ACA = 84.7%, 71.6%, and 46.0%; PMI = 82.1%, 76.8%, and 76.8%, respectively; P = 0.235) was not significantly different. However, the 1-, 3-, and 5-year PTS-free rate was significantly different (ACA = 93.5%, 74.0%, and 55.7%; PMI = 92.9%, 90.0%, and 90.0%, respectively; P = 0.019). There was no significant difference in the rate of other complications. PMI showed a lower incidence of PTS during the follow-up period. Therefore, PMI should be considered as an effective therapeutic modality for patients with iliofemoral DVT.
Cafolla, A; Melizzi, R; Baldacci, E; Pignoloni, P; Dragoni, F; Campanelli, M; Caraccini, R; Foà, R
The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.
Gutierrez-Bernays, David; Ostwald, Matthew; Anstey, Chris; Campbell, Victoria
Regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) has recently been recommended as first-line over heparin. Evidence suggests that RCA prolongs filter life and may reduce bleeding risk, but there is little research on the benefits to dialysis dose delivery or cost, or the effectiveness of transitioning to RCA first-line. The aim of the present study was to assess the effect on dialysis delivery, cost and safety when transitioning from systemic heparin to RCA for first-line anticoagulation for CRRT. A single-center, retrospective observational study was conducted from 2006 to 2012, during which a transition from heparin to a simplified RCA protocol occurred. Demographic and dialysis data, pathology results and costs were obtained. Data were analyzed for both heparin and RCA, and for before and after the transition. 166 patients had 992 dialysis days (heparin 334 vs. RCA 658); demographics were well matched; RCA used less filters per day (P = 0.03), had more days when prescribed dialysis was achieved (85% vs. 60%, P < 0.001), and less filter "down-time" per day (2.4 vs. 6.1 h, P = 0.02). RCA was estimated to cost AU$487 per day, compared to heparin at $479 per day. When the data were analyzed, comparing before and after the transition, these results remained statistically significant. There was no statistical difference in clinical safety events. Transition to first-line RCA was safe, provided more time on filter and consumed less filter circuits using a simple and user friendly protocol. The adjusted cost difference appears negligible. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
Eckman, Mark H
Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.
Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L.
Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receiving AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.
Mas, Jean-Louis; Derumeaux, Geneviève; Amarenco, Pierre; Arquizan, Caroline; Aubry, Pierre; Barthelet, Martine; Bertrand, Bernard; Brochet, Eric; Cabanes, Laure; Donal, Erwan; Dubois-Randé, Jean-Luc; Durand-Zaleski, Isabelle; Ernande, Laura; Finet, Gérard; Fraisse, Alain; Giroud, Maurice; Guérin, Patrice; Habib, Gilbert; Juliard, Jean-Michel; Leys, Didier; Lièvre, Michel; Lusson, Jean-René; Marcon, François; Michel, Patrick; Moulin, Thierry; Mounier-Vehier, François; Pierard, Luc; Piot, Christophe; Rey, Christian; Rodier, Gilles; Roudaut, Raymond; Schleich, Jean-Marc; Teiger, Emmanuel; Turc, Guillaume; Vuillier, Fabrice; Weimar, Christian; Woimant, France; Chatellier, Gilles
Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. Six hundred and sixty-four patients were included in the study. CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years. The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke. © 2016 World Stroke Organization.
Garwood, Candice L; Korkis, Bianca; Grande, Domenico; Hanni, Claudia; Morin, Amy; Moser, Lynette R
In 2011 we reviewed clinical updates and controversies surrounding anticoagulation bridge therapy in patients with atrial fibrillation (AF). Since then, options for oral anticoagulation have expanded with the addition of four direct oral anticoagulant (DOAC) agents available in the United States. Nonetheless, vitamin K antagonist (VKA) therapy continues to be the treatment of choice for patients who are poor candidates for a DOAC and for whom bridge therapy remains a therapeutic dilemma. This literature review identifies evidence and guideline and consensus statements from the last 5 years to provide updated recommendations and insight into bridge therapy for patients using a VKA for AF. Since our last review, at least four major international guidelines have been updated plus a new consensus document addressing bridge therapy was released. Prospective trials and one randomized controlled trial have provided guidance for perioperative bridge therapy. The clinical trial data showed that bridging with heparin is associated with a significant bleeding risk compared with not bridging; furthermore, data suggested that actual perioperative thromboembolic risk may be lower than previously estimated. Notably, patients at high risk for stroke have not been adequately represented. These findings highlight the importance of assessing thrombosis and bleeding risk before making bridging decisions. Thrombosis and bleeding risk tools have emerged to facilitate this assessment and have been incorporated into guideline recommendations. Results from ongoing trials are expected to provide more guidance on safe and effective perioperative management approaches for patients at high risk for stroke. © 2017 Pharmacotherapy Publications, Inc.
Wang, Zhu; Jiang, Ming-Shan; Zhang, Hai-Long; Weng, Ning-Na; Luo, Xue-Feng; Li, Xiao; Yang, Li
Purpose To determine whether posttransjugular intrahepatic portosystemic shunt (TIPS) placement anticoagulation therapy could benefit patients with cirrhosis and portal vein thrombosis (PVT) from the perspective of a change in portal vein patency status and clinical outcomes. Materials and Methods The study was approved by the institutional review board, and informed consent was obtained from each patient. From October 2012 to February 2014, patients with cirrhosis and PVT who underwent TIPS placement were randomly assigned to the anticoagulation therapy or control group. All patients were followed at 1, 3, 6, and 12 months after the TIPS procedure. Outcome measures were a change of portal vein patency status and clinical measures including gastrointestinal rebleeding, shunt dysfunction, hepatic encephalopathy, and survival. Student t test, χ(2) test, Fisher exact test, Mann-Whitney U test, and logistical regression were applied where appropriate. Results A total of 64 patients were enrolled in the study, with 31 allocated to the anticoagulation group and 33 allocated to the control group. Overall, thrombi were improved in 61 patients (96.8%) after the procedure. PVT recanalization (ie, complete disappearance; reconstruction of cavernous transformation) was achieved in 26 patients (83.9%) in the anticoagulation therapy group and in 23 (71.8%) patients in tthe control group (P = .252). The presence of a superior mesenteric vein thrombus may help predict recanalization failure (unadjusted relative risk = 0.243; 95% confidence interval: 0.070, 0.843; P = .026). Clinical outcomes were also similar between the two groups. Conclusion Anticoagulation therapy may not be necessary in certain patients with PVT because TIPS placement alone can achieve a high persistent recanalization rate. (©) RSNA, 2015.
Harris, Leanne F.; Rainey, Paul; Castro-López, Vanessa; O'Donnell, James S.; Killard, Anthony J.
Millions of patients worldwide are receiving anticoagulant therapy to treat hypercoagulable diseases. While standard testing is still performed in the central laboratory, point-of-care (POC) diagnostics are being developed due to the increasing number of patients requiring long-term anticoagulation and with a need for more personalized and targeted therapy. Many POC devices on the market focus on clot measurement, a technique which is limited in terms of variability, highlighting the need for more reliable assays of anticoagulant status. The anti-Xa assay, a factor specific optical assay, was developed to measure the extent to which exogenous factor Xa (FXa) is inhibited by heparinantithrombin complexes. We have developed a novel microfluidic device and assay for monitoring the effect of heparin anticoagulant therapy at the point-of-care. The assay which was also developed in our institute is based on the anti-Xa assay principle but uses fluorescence as the method of detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor®, which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure heparin in human plasma samples from 0 to 0.8 U/ml, with average assay reproducibility of 8% and a rapid result obtained within 60 seconds. Results indicate that with further development, the fluorogenic anti-Xa assay and device could become a successful method for monitoring anticoagulant therapy.
Boltz, Melissa M; Podany, Abigail B; Hollenbeak, Christopher S; Armen, Scott B
Fall risk for older adults is a multi-factorial public health problem as 90% of geriatric injuries are caused by traumatic falls. The CDC estimated 33% of adults >65 years incurred a fall in 2011, with 30% resulting in moderate injury. While much has been written about overall risk to trauma patients on oral anticoagulant (OAC) therapy, less has been reported on outcomes in the elderly trauma population. We used data from the National Trauma Data Bank (NTDB) to identify the types of injury and complications incurred, length of stay, and mortality associated with OACs in elderly patients sustaining a fall. Using standard NTDB practices, data were collected on elderly patients (≥65 years) on OACs with diagnosis of fall as the primary mechanism of injury from 2007 to 2010. Univariate analysis was used to determine patient variables influencing risk of fall on OACs. Odds ratios were calculated for types of injury sustained and post-trauma complications. Logistic regression was used to determine mortality associated with type of injury incurred. Of 118,467 elderly patients sampled, OAC use was observed in 444. Predisposing risk factors for fall on OACs were >1 comorbidity (p<0.0001). Patients on OACs were 188% and 370% more likely to develop 2 and >3 complications (p<0.0001); the most significant being ARDS and ARF (p<0.0001). The mortality rate on OACs was 16%. Injuries to the GI tract, liver, spleen, and kidney (p<0.0002) were more likely to occur. However, if patients suffered a mortality, the most significant injuries were skull fractures and intracranial haemorrhage (p<0.0001). Risks of anticoagulation in elderly trauma patients are complex. While OAC use is a predictor of 30-day mortality after fall, the injuries sustained are markedly different between the elderly who die and those who do not. As a result there is a greater need for healthcare providers to identify preventable and non-preventable risks factors indicative of falls in the anti-coagulated elderly
Altman, R; Rouvier, J; Gurfinkel, E; D'Ortencio, O; Manzanel, R; de La Fuente, L; Favaloro, R G
After cardiac valve replacement patients were blindly randomized into two groups, both receiving aspirin (330 mg) and dipyridamole (75 mg) twice daily and the oral anticoagulant acenocoumarol (Sintrom). An international normalized ratio of 2.0 to 2.99 was assigned to group A and 3.0 to 4.5 to group B; both groups were subsequently analyzed for thromboembolic and hemorrhagic complications. Final evaluation included 51 and 48 patients, respectively. The follow-up was 626 months for group A (12.3 months/patient) and 486 months for group B (10.1 months/patient). The frequency of thromboembolism was equal in both groups: one transient ischemic attack in group A (a rate of 1.92/100 patient-years) and two transient ischemic attacks in group B (a rate of 4.94/100 patient-years). There was, however, a statistical difference in bleeding complications between the two groups (p less than 0.02). Two patients bled in group A, a rate of 3.9% (3.8/100 patient-years), which represents an incidence of one episode each 25.6 years of treatment; 10 patients bled in group B, a rate of 20.8% (24.7/100 patient-years) representing an incidence of one episode each 4 years of treatment. We conclude that an international normalized ratio of 2 to 3 is safer than a ratio of 3 to 4.5 and confers good protection from thromboembolism when oral anticoagulant therapy is used conjointly with platelet function-inhibiting drugs in patients with mechanical substitute heart valves.
Behranwala, K A; Tisdall, M; Habib, N H; Canelo, R
We report on a case of bilateral subcapsular hematoma of the liver, occurring during treatment with warfarin. A 64-year-old woman was put on long-term warfarin therapy. After a bout of severe right hypochondriac pain, computed tomography (CT) scan showed subcapsular hematoma of the liver. Subsequent CT scan, conservative policy only, showed regression of the hematoma. The patient was discharged from the hospital on the 23rd day. We conclude that a nonruptured spontaneous liver hematoma should not be surgically removed. A conservative management with close observation is the mainstay therapy. A switch from warfarin therapy to another anticoagulation therapy is strongly suggested.
Bosch, Luis Ángel Bermúdez
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
Bingham, Angela L; Brown, Rex O; Dickerson, Roland N
We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.
Dézsi, Csaba András; Dézsi, Balázs Bence; Dézsi, András Döme
The perioperative management of patients treated with antithrombotic medications who undergo surgical procedures represents a common clinical problem. Dental interventions are usually associated with a low risk of bleeding; however, the dental implications of new antithrombotic agents are not yet fully understood. The present review is based on the latest evidence and recommendations published on the periprocedural management of dental patients treated with single or dual antiplatelet therapy, vitamin K antagonists, or direct oral anticoagulants for a variety of indications.
Background Oral anticoagulant therapy (OAT) involves many health care disciplines. Even though collaboration between care professionals is assumed to improve the quality of OAT, very little research has been done into the practice of OAT management to arrange and manage the collaboration. This study aims to identify the problems in collaboration experienced by the care professionals involved, the solutions they proposed to improve collaboration, and the barriers they encountered to the implementation of these solutions. Methods In the Netherlands, intensive follow-up of OAT is provided by specialized anticoagulant clinics (ACs). Sixty-eight semi-structured face-to-face interviews were conducted with 103 professionals working at an AC. These semi-structured interviews were transcribed verbatim and analysed inductively. Wagner's chronic care model (CCM) and Cabana's framework for improvement were used to categorize the results. Results AC professionals experienced three main bottlenecks in collaboration: lack of knowledge (mostly of other professionals), lack of consensus on OAT, and limited information exchange between professionals. They mentioned several solutions to improve collaboration, especially solutions of CCM's decision support component (i.e. education, regular meetings, and agreements and protocols). Education is considered a prerequisite for the successful implementation of other proposed solutions such as developing a multidisciplinary protocol and changing the allocation of tasks. The potential of the health care organization to improve collaboration seemed to be underestimated by professionals. They experienced several barriers to the successful implementation of the proposed solutions. Most important barriers were the lack motivation of non-AC professionals and lack of time to establish collaboration. Conclusions This study revealed that the collaboration in OAT is limited by a lack of knowledge, a lack of consensus, and a limited information
Kawabata, Mihoko; Sasaki, Takeshi; Maeda, Shingo; Shirai, Yasuhiro; Yamauchi, Yasuteru; Nitta, Junichi; Goya, Masahiko; Hirao, Kenzo
Direct oral anticoagulants (DOACs) have been shown to be safe and effective for the prevention of stroke in nonvalvular atrial fibrillation (NVAF) patients, however, experience with peri-AF ablation management of DOACs is scarce. This study aimed to investigate the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing paroxysmal non-valvular AF (NVAF) ablation using radiofrequency energy.This study was a multicenter, prospective pilot study. In paroxysmal NVAF patients, rivaroxaban (15 mg or 10 mg once-daily) was started at least 4 weeks prior to AF ablation, discontinued on the day of the procedure, resumed within 24 hours after ablation, and continued at least 3 months afterwards. During the interruption of rivaroxaban, bridging anticoagulation therapy with unfractionated heparin was given. Follow-up of the patients continued for 3 months.A total of consecutive 74 patients (mean age, 62 ± 9 years, 58 [78.4%] male) were enrolled. The mean follow-up period was 108 ± 79 days. Their mean CHADS2 score and CHA2DS2-VASc score were 1.2 ± 1.0 and 0.6 ± 0.7, respectively. Their mean HAS-BLED score was 1.0 ± 0.8. Neither major bleeding nor thromboembolic events, except in a case with bleeding from gastric cancer (1.4%), were observed in the periprocedural period of the AF ablation.The present multicenter study demonstrated the safety and feasibility of periprocedural anticoagulation therapy with rivaroxaban in Japanese patients undergoing catheter ablation of paroxysmal NVAF.
Saito, Kimitoshi; Washino, Satoshi; Nakamura, Yuhki; Konishi, Tsuzumi; Ohshima, Masashi; Arai, Yoshiaki; Miyagawa, Tomoaki
To assess whether hemorrhagic complications associated with transperineal prostate biopsy increased in patients on antiplatelet and/or anticoagulant therapy. In total, 598 consecutive patients underwent transperineal prostate biopsy. The medication group comprised patients who took anti-thromboembolic agents, and the control group comprised those who did not take these agents. No anti-thromboembolic agent was stopped before, during, or after prostate biopsy in the medication group. Complications developing in both groups were compared and classified using the modified Clavien classification system. Subgroup analyses to compare complications in patients taking single antiplatelet, single anticoagulant, and dual antiplatelet and/or anticoagulant agents, and multivariate analyses to predict bleeding risk were also performed. Of the 598 eligible patients, 149 comprised the medication group and 449 comprised the control group. Hematuria (Grade I) developed in 88 (59.1%) and 236 (52.5%) patients in the medication and control group, respectively (p = 0.18). Clot retention (Grade I) was more frequently observed in the medication group than the controls (2.0% versus 0.2%, respectively, p < 0.05). Hospitalization was more frequently prolonged in the medication than the control group (4.0% versus 0.4% of patients, respectively). No complication of Grade III or higher developed in either group. Hematuria was more frequent in patients taking a single anticoagulant (p = 0.007) or two anti-thromboembolic agents (p = 0.04) compared with those taking a single antiplatelet agent. Other complications were generally similar among the groups. In the multivariate analysis, taking more than two anti-thromboembolic agents was the only significant risk factor for bleeding events. No severe complication developed after the transperineal biopsies in either group, although minor bleeding was somewhat more frequent in the medication group. It may not be necessary to discontinue
Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.
Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping
When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.
Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant
Glueck, Charles J.; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping
Background: When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. Case Presentation: A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. Conclusion: When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation. PMID:27536705
Miklaszewska, Monika; Korohoda, Przemysław; Zachwieja, Katarzyna; Kobylarz, Krzysztof; Stefanidis, Constantinos J; Sobczak, Alina; Drożdż, Dorota
As continuous renal replacement therapy (CRRT) has emerged as a standard therapy in pediatric intensive care units (PICU), many related issues that may have an impact on circuit survival have gained in importance. Objective of the study was an evaluation of factors associated with circuit survival, including anticoagulation (ACG). Retrospective study that included 40 patients, who in total received 7636 hours of CRRT during 150 sessions (84 filters, 4260 hours with heparin anticoagulation (Hep-ACG); 66 filters, 3376 hours with regional citrate anticoagulation (RCA)). The Kaplan-Meier analysis of the total circuit survival time depending on the type of ACG did not demonstrate a significant difference between Hep-ACG and RCA. The percentage of clotted filters was significantly higher in case of smaller filters (HF20: 58.8%; ST60: 29.5%; ST100: 15.8%), and their lifetime was significantly lower regardless of ACG (the mean and median lifetime for HF20: 38.7/27.0 h; for ST60: 54.1/72.0 h., for ST100: 62.1/72.0 h, respectively). Irrespectively of filter size, filter clotting occurs within the first 24 hours after the initiation of CRRT. Most commonly, clotting affects small filters, and their lifetime is significantly shorter as compared to larger filters regardless of the type of the ACG. © 2017 The Author(s). Published by S. Karger AG, Basel.
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.
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
The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. 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 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 hours 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 hours 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).
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
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
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
Sufian, Shekeeb; Arnez, Alejandro; Labropoulos, Nicos; Lakhanpal, Sanjiv
The purpose of this study was to evaluate the risks of bleeding, deep venous thrombosis (DVT), endovenous heat induced thrombosis (EHIT) and failure of ablation on patients who undergo ablation while on oral anticoagulation. We compared 378 (3.4%) out of 11252 patients (group A) who had undergone 724 endovenous ablation of the saphenous veins from January 1, 2011 to September 30, 2014 while on oral anticoagulation to a randomly selected 375 patients (group B) who underwent 641endovenous ablation in the same time period but were not on anticoagulation. The demographic data, history of DVT, the Clinical, Etiologic, Anatomic, Pathologic (CEAP) classification and the VCSS (Venous Clinical Severity Score) scores were analyzed. The indications for anticoagulation, the anticoagulants used were recorded. The primary endpoints were bleeding, development of DVT or EHIT, and failure of ablation. Patients in group A were older, had more men, more history of DVT and PE, had higher CEAP and VCSS scores compared to group B. The type of anticoagulation used was warfarin in 77.2% direct oral inhibitors (DOIs) in 22.8%. The rate of failure of ablation at 3 days was 39 (5.6%) for Group A and 3 (0.5%) for Group B (P<0.0001) and at one month it was 46 (10.1%) vs. 27 (6.7%) (P=0.086). The number of EHIT cases in group A at 3 days was 2 (0.3%), compared to 6 (0.9%) in group B (P=0.016) and at 1 month it was 0 compared to 4 (1.0%) (P=0.0483). The DVT, SVT, hematoma and wound infection rates were similar in the two groups. Ablation of the saphenous veins in patients who are on oral anticoagulation is safe and does not increase the risk of bleeding or hematoma, but it may slightly lower the incidence of EHIT and increase the incidence of failure of ablation.
Shah, Syed Ghulam Sarwar; Robinson, Ian
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. 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. 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. 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 particularly for patients with chronic
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
Nieto, J A; Solano, R; Ruiz-Ribó, M D; Ruiz-Gimenez, N; Prandoni, P; Kearon, C; Monreal, M
Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain. Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient's risk of fatal bleeding during the first 3 months of treatment. Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility > or = 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 x 10(9) L(-1) (OR, 2.23), creatinine clearance < 30 mL min(-1) (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11-0.23) of the low-risk, 1.06% (95% CI, 0.85-1.30) of the moderate-risk, and 4.24% (95% CI, 2.76-6.27) of the high-risk category. Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.
CORRIGENDUM to Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant
Owing to errors made by the authors, Charles J. Glueck, Kevin Lee, Marloe Prince, Vybhav Jetty, Parth Shah, and Ping Wang, the following article contains errors. Glueck CJ, Lee K, Prince M, et al. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant. J Investig Med High Impact Case Rep. 2016;4(3):1-6. doi: 10.1177/2324709616661833 PMID:28321420
Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Shinozaki, Eiji; Matsusaka, Satoshi; Ozaka, Masato; Ogura, Mariko; Chin, Keisho; Yamaguchi, Toshiharu
Background Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev). We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings. Methods Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E), thrombus >40 mm in diameter (S), thrombus involving the superior vena cava (C), and decreased blood flow (V). Results Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9%) by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%). Of these 56 patients, 11 (19.6%) received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%), as well as V in two (18.2%), S + V + C in one (9.1%), E + S + V in one (9.1%), E + C in one (9.1%), E in one (9.1%), and C in one (9.1%). All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%). Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%), but there were no treatment-related severe adverse events or deaths. Severe thromboembolism was not observed in the other 68 patients. Conclusion Our anticoagulant protocol for asymptomatic thrombosis detected by Doppler ultrasound imaging was effective at preventing severe
Roncon, Loris; Azzarito, Michele; Becattini, Cecilia; Bongarzoni, Amedeo; Casazza, Franco; Cuccia, Claudio; D’Agostino, Carlo; Rugolotto, Matteo; Vatrano, Marco; Vinci, Eugenio; Fenaroli, Paride; Formigli, Dario; Silvestri, Paolo; Nardi, Federico; Vedovati, Maria Cristina; Scherillo, Marino
Abstract The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the ‘double drug single dose’ approach or with ‘single drug double dose’; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer. PMID:28751847
Jurcuţ, Ruxandra; Militaru, Sebastian; Geavlete, Oliviana; Drăgotoiu, Nic; Sipoş, Sergiu; Roşulescu, Răzvan; Ginghină, Carmen; Jurcuţ, Ciprian
Background Patient adherence is an essential factor in obtaining efficient oral anticoagulation using vitamin K antagonists (VKAs), a situation with a narrow therapeutic window. Therefore, patient education and awareness are crucial for good management. Auditing the current situation would help to identify the magnitude of the problem and to build tailored education programs for these patients. Methods This study included 68 hospitalized chronically anticoagulated patients (mean age 62.6±13.1 years; males, 46%) who responded to a 26-item questionnaire to assess their knowledge on VKA therapy management. Laboratory and clinical data were used to determine the international normalized ratio (INR) at admission, as well as to calculate CHA2DS2-VASC and HAS-BLED scores for patients with atrial fibrillation. Results The majority of patients (62%) were receiving VKA for atrial fibrillation, the others for a mechanical prosthesis and previous thromboembolic disease or stroke. In the atrial fibrillation group, the mean CHA2DS2-VASC score was 3.1±1.5, while the average HAS-BLED score was 1.8±1.2. More than half of the patients (53%) had an INR outside of the therapeutic range at admission, with the majority (43%) having a low INR. A correct INR value was predicted by education level (higher education) and the diagnostic indication (patients with mechanical prosthesis being best managed). Patients presenting with a therapeutic INR had a trend toward longer treatment duration than those outside the therapeutic range (62±72 months versus 36±35 months, respectively, P=0.06). There was no correlation between INR at admission and the patient’s living conditions, INR monitoring frequency, and bleeding history. Conclusion In a tertiary cardiology center, more than half of patients receiving VKAs are admitted with an INR falling outside the therapeutic range, irrespective of the bleeding or embolic risk. Patients with a mechanical prosthesis and complex antithrombotic regimens
Mazzaccara, Cristina; Conti, Valeria; Liguori, Rosario; Simeon, Vittorio; Toriello, Mario; Severini, Angelo; Perricone, Corrado; Meccariello, Alfonso; Meccariello, Pasquale; Vitale, Dino Franco; Filippelli, Amelia; Sacchetti, Lucia
Background and Aim Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice. Materials and Methods A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9*2,*3, CYP4F2*3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure. Results Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9*3 (11.8%), age (8.5%), CYP2C9*2 (3.5%), gender (2.0%) and lastly CYP4F2*3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R2 = 0.805 and p<0.001; R2 = 0.773, respectively). Conclusions Our algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy. PMID:23990957
Cho, Yong-Wook; Kim, Euiseong
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.
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
von Schéele, Birgitta; Fernandez, Maria; Hogue, Susan Lynn; Kwong, Winghan Jacqueline
To summarize the available evidence on the issues in health economics related to oral anticoagulation for stroke prevention in atrial fibrillation (AF) in the US. A literature review was performed using PubMed, EMBASE, Cochrane Library, and International Pharmaceutical Abstracts, as well as the websites of professional organizations. The search was conducted according to a prespecified protocol, limiting articles to those published in English from 2001 to October 2012 and focused on the economics associated with AF and AF-related stroke in the US. Data from 27 studies were extracted and included in the review. Strokes in patients with AF are more debilitating and have higher recurrence rates and mortality compared with strokes unrelated to AF. However, data describing the long-term cost of AF-related stroke and stroke subtypes remain limited. The costs of major gastrointestinal (GI) bleeding and intracranial bleeding related to warfarin are significant, whereas the costs of the more frequent minor GI bleeding are relatively low. Overall, the cost-effectiveness of warfarin versus aspirin or no treatment in patients with at least 1 risk factor for stroke is well established. Economic evaluations based on results from randomized controlled clinical trials generally found that new anticoagulants were a cost-effective alternative to warfarin for stroke prevention in AF. However, these cost-effectiveness results are highly sensitive to how well optimal international normalized ratio control is maintained (within target of 2.0-3.0) for warfarin and the time horizon used for analysis. Time in therapeutic range for warfarin in routine clinical practice was lower than in clinical trials, as shown by previous studies. This review identified several areas of uncertainty regarding the economic benefit of anticoagulants. The generalizability of cost-effectiveness results of anticoagulant therapy in AF based on clinical trial data must be confirmed by comparative effectiveness
Ghaly, Ramsis F.; Lissounov, Alexei; Candido, Kenneth D.; Knezevic, Nebojsa Nick
Background: Spinal cord stimulators (SCSs) are gaining increasing indications and utility in an expanding variety of clinical conditions. Complications and initial expenses have historically prevented the early use of SCS therapy despite ongoing efforts to educate and promote its utilization. At present, there exists no literature evidence of SCS implantation in a chronically anticoagulated patient, and neuromodulation manufacturers are conspicuously silent in providing warnings or recommendations in the face of anticoagulant use chronically. It would appear as through these issues demand scrutiny and industry as well as neuromodulation society advocacy and support in terms of the provision of coherent guidelines on how to proceed. Case Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Conclusion: Our literature search did not reveal any
Oldgren, Jonas; Wallentin, Lars; Alexander, John H; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan
Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.
Tung, Matthew K; Ramkumar, Satish; Cameron, James D; Pang, Benjamin; Nerlekar, Nitesh; Kotschet, Emily; Alison, Jeffrey
Anticoagulant and antiplatelet therapy are recommended following WATCHMAN implantation (45 days and 6 months) to reduce the risk of embolic events. These patients are often also at high risk of recurrent bleeding complications. We aimed to assess the safety of reduced duration of treatment with anticoagulant and antiplatelet therapy in the early post implant period. This was a retrospective cohort study assessing the duration of antiplatelet and anticoagulant therapy in 47 consecutive patients following WATCHMAN implant. The primary outcome was rate of major bleeding, stroke and systemic embolic complications. The secondary endpoints were rate of device thrombus and peri-device leak >4mm as assessed by transoesophogeal echocardiography. Forty-seven patients were followed up for a mean of 2.4+/-1.7 years (111.4 total patient-years). The rate of stroke was 1.8/100 patient-years (two events) and the rate of major bleeding complication was 8.9/100 patient-years. Three patients had peri-device leak >4mm and no patients had device thrombus visualised. 70.2% of patients had discontinued anticoagulation at 45 days, 89.4% had discontinued dual antiplatelet therapy at 90 days. Seven patients were not on any form of anticoagulant or antiplatelet at five months. Comparison of probability of survival free from stroke by time of cessation of anticoagulant and antiplatelet therapy demonstrated no significant differences (p-value for log rank test 0.238 and 0.820). Following WATCHMAN implant shortened periods of anticoagulants and antiplatelets may be considered, particularly in the context of high bleeding risk. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.
Martínez-Taboada, Víctor Manuel; López-Hoyos, Marcos; Narvaez, Javier; Muñoz-Cacho, Pedro
To evaluate the effect of antiplatelet/anticoagulant therapy on the occurrence of severe ischemic complications in GCA patients at diagnosis and while on treatment with corticosteroids (CS), and the risk of bleeding in these patients. A comprehensive search of PubMed and the Cochrane Central Register of Controlled Trials databases was completed and supplemented by hand searching of the references of all selected articles published from 1992 through December 2012. The cumulative meta-analysis included 6 retrospective studies that provided a total of 914 GCA patients. The effect of established antiplatelet/anticoagulant therapy on the occurrence of severe ischemic complications in patients with GCA at diagnosis and on the development of new severe ischemic complications in patients with GCA after diagnosis and while on treatment with CS were evaluated; as well as the risk of bleeding in patients with GCA on concomitant treatment with CS and antiplatelet/anticoagulant therapy. Antiplatelet/anticoagulant therapy before the diagnosis of GCA was not associated with a protection to develop severe ischemic complications (OR: 0.661; 95% CI [0.287-1.520]; p=0.33). However, such a therapy may prevent from severe ischemic complications after the diagnosis of GCA (OR: 0.318; [0.101-0.996]; p=0.049) without increasing the risk of bleeding in patients with GCA on concomitant treatment with CS (OR: 0.658; [0.089-4.856]; p=0.682). Antiplatelet/anticoagulant therapy prior to the diagnosis of GCA was not associated with reduction in severe ischemic complications. However, antiplatelet/anticoagulant therapy demonstrated a marginal benefit when used together with CS therapy in patients with established GCA without associated bleeding risk. Copyright © 2014 Elsevier B.V. All rights reserved.
ENOMOTO, Yukiko; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; EGASHIRA, Yusuke
To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patient's data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p < 0.001), hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5% vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p < 0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001, postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients. PMID:24305029
Kruse-Loesler, Birgit; Kelker, Matthias; Kleinheinz, Johannes
Background Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure. Methods On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results. Results Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR. Conclusion This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery. PMID:16316464
GLOVER, R P; KUZELL, W C
A micro technique that is here described for "prothrombin time" determinations, employing capillary whole blood, provides a range of values which is closely correlated with the Quick one-stage plasma method, thus providing inter-changeability of results both in normal persons and in patients who have been treated with anticoagulant drugs. Avoidance of the use of a water bath and centrifuge permit this technique to yield immediate results at the bedside, in the office or in the patient's home. The use of a whole blood instead of a plasma technique lends additional safety to control of anticoagulant medication, since it may reflect depression of clotting factors not apparent by the usual plasma methods.
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.
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
Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker
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.
Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie
Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers' perceptions of what patients should know, rather than on patients' preferences. To investigate patients' viewpoints on educational needs and preferred modalities of information delivery. We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30-2.46). Pharmacists (1.69, 1.58-1.80), nurses (1.05, 0.95-1.16), and patient associations (0.36, 0.29-0.44), along with group sessions (0.85, 0.75-0.95), the internet (0.77, 0.67-0.88), and delivery of material at the patient's home (1.26, 1.14-1.38), were ranked poorly in terms of delivering educational material. This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their effectiveness.
Lai, Jonathan; Ramai, Daryl; Alchi, Ramiz; Bloomfield, Dennis
Patients with protein C deficiency are at increased risk for thrombolic diseases. Non-vitamin K antagonist anticoagulant options should be considered in patients with warfarin-induced skin necrosis (WISN) in the setting of protein C. We report a 41-year-old African American male patient with WISN and protein C deficiency who was treated with rivaroxaban followed by dabigatran. After 1 month on rivaroxaban, he began experiencing blood in his stools, unrelenting pain in his lower extremities, found it difficult to obtain medication despite having insurance and as a result did not maintain compliance. He was then assessed at the hospital, symptomatically treated and discharged on dabigatran. After 6 weeks, he reported symptomatic relief and less side effects. This case involved a head-to-head clinical comparison of rivaroxaban and dabigatran as alternatives to warfarin anticoagulation therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Franke, Curtis A; Dickerson, Lori M; Carek, Peter J
Many patients in primary care require anticoagulation with warfarin for the prevention of venous and systemic embolism. Achieving the goal international normalized ratio (INR) with warfarin is challenging. The purpose of this quality improvement initiative was to increase the proportion of patients taking warfarin with an INR value within the goal range. We included all patients identified on an anticoagulation log in the family medicine residency practice during 3 time periods: baseline, after point-of-care (POC) testing was initiated (intervention period 1), and after a standardized warfarin-dosing protocol was implemented (intervention period 2). Educational sessions were conducted during each intervention period. Measures included the frequency of INR monitoring and the percentage of office visits in which patients' values were within the goal INR range. Data were analyzed using descriptive statistics, the Student t test, and the chi2 test. At baseline, patients had an average of 2.6 INR tests performed, and 30.8% were within the INR goal range. Using POC testing, the frequency of monitoring increased to 4.3 INR tests per patient (P = .04), but the percentage of patients within the INR goal remained low at 32.1% (P=.88). When physicians implemented the standardized protocol to guide warfarin dosing, the frequency of testing was similar (3.8 tests per patient), but the percentage of patients within the INR goal increased to 45.9% (P<.04). POC testing increased the frequency of INR testing, and additional use of a standardized protocol for warfarin dosing increased the percentage of patients within the INR goal range. This model of anticoagulation management could be easily implemented in any family medicine office.
Spyropoulos, Alex C; Jenkins, Patti; Bornikova, Larissa
Traditional perioperative bridge therapy for patients receiving long-term oral anticoagulation involves weight-adjusted intravenous unfractionated heparin (UFH) in the perioperative period during temporary discontinuation of the oral anticoagulant. We sought to determine whether an alternate strategy of outpatient-based perioperative disease management with low-molecular-weight heparin (LMWH) as bridge therapy provides the potential for cost savings. Retrospective review of all clinic notes from an anticoagulation clinic. An integrated, staff-model health maintenance organization. Patients receiving long-term warfarin therapy from January 1998-March 2002 who received perioperative bridge therapy with the LMWH enoxaparin 1 mg/kg twice/day subcutaneously A total of 126 bridge therapy encounters in 84 patients receiving LMWH as perioperative bridge therapy were identified, with 48 of those encounters involving patients with at least one mechanical heart valve. A total of 1108 hospital bed days were saved. Based on 1996 cost estimates, the total approximate cost savings for the 4.25 years of the outpatient bridge therapy program was dollars 903,020. No thrombotic events were reported. Three major hemorrhagic events that required discontinuation of LMWH were reported. Outpatient-based disease management protocols and the LMWH enoxaparin as bridge therapy during temporary discontinuation of warfarin for an elective surgical procedure resulted in cost savings of approximately dollars 212,475/year in an integrated health maintenance organization. In addition, this strategy appears both safe and effective.
Tan, Tricia MM; Caputo, Carmela; Mehta, Amrish; Hatfield, Emma CI; Martin, Niamh M; Meeran, Karim
Background Pituitary apoplexy is a life-threatening endocrine emergency that is caused by haemorrhage or infarction of the pituitary gland, commonly within a pituitary adenoma. Patients classically present with headache, ophthalmoplegia, visual field defects and altered mental state, but may present with a typical symptoms such as fever and altered conscious level. Case presentation A 57-year-old female with a known pituitary macroadenoma was treated for suspected acute coronary syndrome with aspirin, clopidogrel and full dose enoxaparin. She developed a severe and sudden headache, nausea and vomiting and visual deterioration. A CT scan showed haemorrhage into the pituitary macroadenoma. She underwent neurosurgical decompression. Post-operatively her visual fields and acuity returned to baseline. She was continued on hydrocortisone and thyroxine replacement on discharge. Conclusion This case illustrates the risks of anticoagulation in a patient with a known pituitary macroadenoma, and raises the issue of whether these tumours present a relative contraindication to the use of dual antiplatelet and anticoagulation in acute coronary syndrome. PMID:17761001
Pink, J; Pirmohamed, M; Lane, S; Hughes, D A
Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.
Iba, Toshiaki; Thachil, Jecko
In sepsis, the coagulation system is often systemically activated in combination with the simultaneous impairment of fibrinolysis and anticoagulant systems. Since this hypercoagulable state often leads to disseminated intravascular coagulation (DIC), an independent predictor of mortality in critically ill patients, the appropriate management of DIC itself is a crucial part of treatment strategies for severe sepsis. In this context, the Japanese Association of Acute Medicine (JAAM) scoring system for DIC has been proposed as a valid test for diagnosing DIC; this system is also expected to aid in devising specifically tailored management strategies. Anticoagulant therapy is commonly given to septic patients with DIC as part of the standard care in Japan. More recently, antithrombin concentrate and recombinant thrombomodulin have become the two major anticoagulant agents of choice. In relation to the use of antithrombin, recent studies have indicated that the recovery of antithrombin activity to within the normal range (>70%) is necessary if supplementation therapy is to provide a favorable outcome. Recombinant thrombomodulin is slightly more controversial, with favorable results being greater among severe cases of DIC. In the present review, we summarize recent clinical advances in anticoagulant therapy for sepsis-associated DIC.
Min, Jiangyong; Farooq, Muhammad Umar
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.
Oldgren, Jonas; Wallentin, Lars; Alexander, John H.; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan
Background Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. Methods and results All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. Conclusion In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with
Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Çağrı; Kalaycıoğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalçık, Macit; Yaman, Mehmet; İnci, Sinan; Altıntaş, Bernas; Kalkan, Sedat; Kırma, Cevat; Biteker, Murat
The definition of non-valvular atrial fibrillation (NVAF) is controversial. We aimed to assess the impact of valvular heart disease on stroke prevention strategies in NVAF patients. The RAMSES study was a multicenter and cross-sectional study conducted on NVAF patients (ClinicalTrials.gov identifier NCT02344901). The study population was divided into patients with significant valvular disease (SVD) and non-significant valvular disease (NSVD), whether they had at least one moderate valvular disease or not. Patients with a mechanical prosthetic valve and mitral stenosis were excluded. Baseline characteristics and oral anticoagulant (OAC) therapies were compared. In 5987 patients with NVAF, there were 3929 (66%) NSVD and 2058 (34%) SVD patients. The predominant valvular disease was mitral regurgitation (58.1%), followed by aortic regurgitation (24.1%) and aortic stenosis (17.8%). Patients with SVD had higher CHA2DS2VASc [3.0 (2.0; 4.0) vs. 4.0 (2.0; 5.0), p < 0.001] and HAS-BLED [2.0 (1.0; 2.0) vs. 2.0 (1.0; 2.0), p = 0.004] scores compared to patients with NSVD. Overall, 2763 (71.2%) of NSVD and 1515 (73.8%) of SVD patients were on OAC therapy (p = 0.035). When the patients with SVD were analyzed separately, the mean CHA2DS2VASc and HAS-BLED scores were higher in patients with mitral regurgitation compared to patients with aortic regurgitation and aortic stenosis [4.0 (3.0; 5.0), 3.0 (2.0; 4.0), 3.0 (2.0; 4.0) p < 0.001 and 2.0 (1.0; 3.0), 1.0 (1.0; 2.0), 1.0 (0.0; 2.0) p < 0.001, respectively]. In patients with SVD, 65.7% of mitral regurgitation, 82.6% of aortic regurgitation and 88.0% of aortic stenosis patients were on OAC therapy. One out of three NVAF patients had at least one moderate valvular heart disease with the predominance of mitral regurgitation. Patients with SVD were at greater risk of stroke and bleeding compared to patients with NSVD. Although patients with mitral regurgitation should be given more aggressive anticoagulant therapy
Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie
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
Introduction Regional citrate anticoagulation is safe, feasible and increasingly used in critically ill patients on continuous renal replacement therapy (CRRT). However, in patients with hepatic or multi-organ dysfunction, citrate accumulation may lead to an imbalance of calcium homeostasis. The study aimed at evaluating the incidence and prognostic relevance of an increased total to ionized calcium ratio (T/I Ca2+ ratio) and its association to hepatic dysfunction. Methods We performed a prospective observational study on n = 208 critically ill patients with acute kidney injury (AKI) and necessity for CRRT with regional citrate anticoagulation (CRRT-citrate) between September 2009 and September 2011. Critical illness was estimated by Simplified Acute Physiology Score II; hepatic function was measured with indocyanine green plasma disappearance rate. After achieving a steady state of calcium homeostasis patients were classified into tertiles according to the T/I Ca2+ ratio (<2.0 versus 2.0 - 2.39 versus ≥2.4). Results The T/I Ca2+ ratio was determined as an independent predictor for 28-day mortality in critically ill patients with AKI on CRRT-citrate confirmed by receiver operating characteristics and multivariate analysis (Area under the curve 0.94 ± 0.02; p<0.001). A T/I Ca2+ ratio ≥2.4 independently predicted a 33.5-fold (p<0.001) increase in 28-day mortality-rate. There was a significant correlation between the T/I Ca2+ ratio and the hepatic clearance (p<0.001) and the severity of critical illness (p<0.001). The efficacy and safety of citrate anticoagulation, determined by blood urea nitrogen, mean filter patency and bleeding episodes, were not significantly different between the tertiles. Conclusions In patients on CRRT-citrate T/I Ca2+ ratio is closely related to the clinical outcome and emerged as an independent predictor of 28-day mortality. Larger studies are required to define the cut-off and predictive value for the T/I Ca2+ ratio. This ratio is
Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison
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
Daniels, Lisa M; Barreto, Jason N; Kuth, John C; Anderson, Jeremy R; Zhang, Beilei; Majka, Andrew J; Morgenthaler, Timothy I; Tosh, Pritish K
A failure mode and effects analysis (FMEA) was conducted to analyze the clinical and operational processes leading to above-target International Normalized Ratios (INRs) in warfarin-treated patients receiving concurrent antimicrobial therapy. The INRs of patients on long-term warfarin therapy who received a course of trimethoprim-sulfamethoxazole, metronidazole, fluconazole, miconazole, or voriconazole (highly potentiating antimicrobials, or HPAs) between September 1 and December 31, 2011, were compared with patients on long-term warfarin therapy who did not receive any antimicrobial during the same period. A multidisciplinary team of physicians, pharmacists, and a systems analyst was then formed to complete a step-by-step outline of the processes involved in warfarin management and concomitant HPA therapy, followed by an FMEA. Patients taking trimethoprim-sulfamethoxazole, metronidazole, or fluconazole demonstrated a significantly increased risk of having an INR of >4.5. The FMEA identified 134 failure modes. The most common failure modes were as follows: (1) electronic medical records did not identify all patients receiving warfarin, (2) HPA prescribers were unaware of recommended warfarin therapy when HPAs were prescribed, (3) HPA prescribers were unaware that a patient was taking warfarin and that the drug interaction is significant, and (4) warfarin managers were unaware that an HPA had been prescribed for a patient. An FMEA determined that the risk of adverse events caused by concomitantly administering warfarin and HPAs can be decreased by preemptively identifying patients receiving warfarin, having a care process in place, alerting providers about the patient's risk status, and notifying providers at the anticoagulation clinic. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Funk, Dorothy M Adcock
Anticoagulant therapy, including conventional agents and a variety of new oral, fast-acting drugs, is prescribed for millions of patients annually. Each anticoagulant varies in its effect on routine and specialty coagulation assays and each drug may require distinct laboratory assay(s) to measure drug concentration or activity. This review provides an overview of the assorted assays that can measure anticoagulant drug concentration or activity and includes key assay interferences. The effect of these conventional and new anticoagulant agents on specialty coagulation assays used to evaluate for bleeding or clotting disorders, and whether this impact is physiological or factitious, is included. Also provided is a short review of superwarfarin poisoning and features distinguishing this from warfarin overdose. Knowledge of clinically significant pearls and pitfalls pertinent to coagulation assays in relation to anticoagulant therapy are important to optimize patient care.
Harenberg, Job; Jörg, Ingrid; Vukojevic, Yvonne; Mikus, Gerd; Weiss, Christel
To gather information on anticoagulant effects after the termination of long-term therapy with idraparinux. The anticoagulant effects of idraparinux, a synthetic polymethylated analogue of its pentasaccharide, were analysed in 23 patients after termination of a 6- or 12-month therapy period for the prevention of recurrent venous thromboembolism (VTE). Plasma samples of patients initially randomized to 2.5 mg idraparinux (normal creatinine clearance) or 1.5 mg idraparinux (creatinine clearance < 30 ml/min) were investigated in the van Gogh trials. At 3-month intervals for up to 15 months following the termination of the therapy, the factor Xa-specific S2222 chromogenic substrate (aXa) assay and Heptest were used to determine various pharmacokinetic parameters and prothrombin-induced clotting time (PiCT), activated partial thromboplastin time (aPTT) and prothrombin time (PT) were determined. Based on the aXa assay and Heptest, the half lives (t1/2) were 60.2 days and 107.7 days (p < 0.0001), maximum drug concentrations (Cmax) were 0.30 and 0.39 microg/l (p = 0.0016), areas under the activity time curve (AUC) were 33.7 and 38.0 microg/l per day (p = 0.0002), plasma clearances were 0.09 and 0.06 ml/min (p < 0.0001), mean residence times (MRT) were 75.4 and 121.9 (p < 0.0001) and volumes of distribution (Vdiss) were 7.4 and 8.61 (p = 0.1336), respectively. After 12 months of treatment (n = 18), the S2222 and Heptest results showed significantly higher Cmax and AUC, lower Vdiss and clearance and unchanged t1/2 and MRT values compared to 6 months of treatment (n = 5). The PiCT was prolonged for a period of 9 months. Coagulation times of aPTT and PT were not influenced. The results of these parameters did not differ between 12 and 6 months of treatment. The data support reports on a non-ionic binding of idraparinux to antithrombin and other proteins. We suggest that these findings may explain some of the findings of the van Gogh Extension trial.
Zhang, Zhu; Zhai, Zhenguo; Yang, Yuanhua; Wan, Jun; Xie, Wanmu; Zhu, Jianguo; Shen, Ying H; Wang, Chen
Bleeding refers to the most important complication during anticoagulation therapy in patients with pulmonary embolism (PE). However, the incidence and risk factors of bleeding in Chinese population with anticoagulant therapy remains unknown. Although diabetes mellitus (DM) has been demonstrated to increase the risk of PE, little information of its influence on anticoagulation-associated bleeding risk can be available. In our study, 563 acute PE patients, who fulfilled the including criteria were enrolled from a single center and received conventional anticoagulant therapy. And there were 539 patients completed the 3 months following-up. The cumulative incidences of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) were 3.0% (95% CI 1.01-3.05) and 14.0% (95% CI 1.47-5.21), respectively. Besides, anemia (OR 3.52, 95% CI 1.12-11.41) and recent history of MB (OR 8.14, 95% CI 1.41-31.95) were independently associated with MB. Age >65 year (OR 1.51, 95% CI 1.12-3.11), cancer (OR 2.01, 95% CI 1.12-4.01) and therapeutic range (TTR) during 3 months (OR 0.93, 95% CI 0.91-0.98) were independently associated with CRNMB. Additionally, DM was an independent risk factor for both MB (OR 2.11, 95% CI 1.10-4.12) and CRNMB (OR 2.11, 95% CI 1.10-4.12). Notably, the incidence of MB or CRNMB was significantly higher in DM patients than non-DM patients. At the end of 3-month follow-up, the HbA1C in CRNMB group was 8.3%, yet it was 7.0% in non-CRNMB group among diabetic patients (p = 0.04). In conclusions, the bleeding rates are high in patients with acute PE who receive anticoagulant therapy. In addition to the already known bleeding risk factors, DM can also increase the bleeding risk significantly. Thus, good glycemic control may be essential after prescription of anticoagulant therapy.
Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister
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
Smith, Karen; Weeks, Susan
The objective of this systematic review is to synthesize the best available evidence on the impact of pre-injury anticoagulation therapy in the older adult patient who experiences a traumatic brain injury. Trauma in the elderly remains one of the most challenging problems for healthcare providers in the 21 century. The most recent United States (U.S.) census estimates that by the year 2020 more than 52 million Americans will be age 65 years or older, and one million of those will live to be over 100 years of age. In the older adult population, classified as age 65 years or greater, the two leading causes of injury were reported as motor vehicle crashes (MVC) and falls. We have become increasingly aware of the unique physiologic changes in this population that make them more susceptible to succumb to traumatic injuries than their younger counterparts. This is especially true in the anticoagulated patient with a traumatic brain injury.Traumatic brain injury (TBI) is defined as an injury occurring when an external force traumatizes the brain. It may also be known as an intracranial or head injury. TBI is classified depending on the mechanism of injury (blunt or penetrating), severity, and location of the assault. Damage to the brain, skull, and/or scalp transpires. TBI is the leading cause of death and disability in the U.S, and persons of all ages, races, ethnicities, and incomes are affected. In the past five to ten years, trauma services have recorded an increase in major trauma admissions of patients age 65 years and older. In review of the literature to date, it is recognized that outcomes following moderate to severe TBI in older adults are poor, with high rates of significant disability and mortality reported. A recent Australian study reported that 28% of older adults died in the hospital following a TBI and in Finland adults aged 75 years and older had the highest rates of TBI related hospitalizations and death. According to a systematic review of European
Lagi, Alfonso; Spini, Simona; Meucci, Elisa; Cartei, Alessandro; Cencetti, Simone
Background The aim of this study was to investigate the incidence of digestive hemorrhages in patients with non-valvular atrial fibrillation (NVAF), scheduled for oral anticoagulant therapy. Methods We conducted, over 24 months, a prospective, randomized, population-based observational study on consecutive patients with recurrent paroxysmal, persistent, or permanent NVAF, scheduled for oral anticoagulant therapy. The study initially included 268 patients with NVAF (162 males and 106 females) with a mean age of 74 years (range 42-86 years). Patients were split into two groups: those undergoing preventive Esophago-Gastro-Duodenoscopy (EGD) (Group A) and those who did not (Group B). All patients positive by EGD underwent medical treatment and subsequent 30-day endoscopic controls showed complete healing. The primary outcome of the study was to determine if previous EGD in patients with NVAF resulted in a low risk of bleeding during oral anticoagulant therapy. The two groups were comparable for most variables. Results Significant differences were found between groups for the incidence of antiarrhythmic drugs and for early hemorrhage (P <0.001). The incidences of early hemorrhages were significantly different between the two groups with 12 in group B (12%) and 2 in group A (1.7%). Conclusions Preventive EGD can identify hidden digestive diseases, which may increase the incidence of early hemorrhages.
Park, Kyung-Hyun; Cheon, Sang-Ho; Lee, Ji-Ho
Purpose This study evaluated the incidence of a venous thromboembolism (VTE) after total knee arthroplasty (TKA) using multidetector row computed tomography-indirect venography (MDCT-indirect venography) and assessed the efficacy of anti-coagulation therapy. Materials and Methods We enrolled 118 patients with 126 cases of TKA. The average age of the patients was 68.4 years. We used 64 channel MDCT-indirect venography for the detection of VTE. We treated selectively proximal deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) cases according to the results of MDCT-indirect venography. We re-evaluated the change in VTE using follow-up MDCT-indirect venography after 3 months. Results We identified VTE in 35.7%. DVT only was identified in 22.2% including 8 cases of proximal DVT and 20 cases of distal DVT. PTE without DVT was identified in 4.8%, and combined DVT and PTE in 8.7%. All patients with PTE were asymptomatic, but 4 DVT patients had signs of leg swelling. After anti-coagulation therapy, 20 patients showed complete resolution in 16 cases, improvement in 3 cases and one case showed a new distal DVT. Conclusions The incidence of VTE after primary TKA was 35.7% in Korea. Furthermore, anti-coagulation therapy for proximal DVT and PTE patients may be a useful method for preventing the occurrence of a fatal PTE. PMID:22570848
Nascimento, Bruno Ramos; de Sousa, Marcos Roberto; Demarqui, Fábio Nogueira; Ribeiro, Antonio Luiz Pinho
Objectives. Assess the impact of associating thrombolytics, anticoagulants, antiplatelets, and primary angioplasty (PA) on death, reinfarction (AMI), and major bleeding (MB) in STEMI therapy. Methods. Medline search was performed to identify randomized trials comparing these classes in STEMI treatment, at least 500 patients, providing death, AMI, and MB rates. Similar arms were grouped. Correlation between number of drugs and PA and the outcomes was evaluated, as well as correlation between the year of the study and the outcomes. Results. Fifty-nine papers remained after exclusions. 404.556 patients were divided into 35 groups of arms. There was correlation between the number of drugs and rates of death (r = -0.466, P = 0.005) and MB (r = 0.403, P = 0.016), confirmed by multivariate regression. This model also showed that PA is associated with lower mortality and increased MB. Year and period of publication correlated with the outcomes: death (r = -0.380, P < 0.001), MB (r = 0.212, P = 0.014), and AMI (r = -0.231, P = 0.009). Conclusion. The increasing complexity of STEMI treatment has resulted in significant reduction in mortality along with increased rates of MB. Overall, however, the benefits of treatment outweigh the associated risks of MB.
Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert
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
Burns, Whitney; Koelper, Nathanael; Barberio, Andrea; DeAgostino-Kelly, Mary; Mennuti, Michael; Sammel, Mary D; Dugoff, Lorraine
The objective of this study was to identify maternal characteristics associated with a failed cell-free DNA (cfDNA) test due to a low fetal fraction (FF). Retrospective cohort study of women with singleton pregnancies who had cfDNA screening at 10-25 weeks gestation between October 2011 and January 2016. cfDNA screening was performed using methylation techniques until October 2013; thereafter, samples were run with massively parallel sequencing. Multivariable logistic regression was performed to identify maternal characteristics associated with no cell free DNA result secondary to low FF. Thirty-three (1.2%) of 2890 eligible women had a failed cfDNA test, including 18 (0.6%) cases with a low FF. A failed cfDNA test due to a low FF was associated with obesity (aOR 1.11, CI 1.05-1.18, p = 0.0003) and treatment with enoxaparin (aOR 37.5, 11.19 - 125.87, p <0.0001). 5 of 28 (18%, 95% CI: 6.1%-36.9%) women on enoxaparin had a failed cfDNA test secondary to a low FFx. Enoxaparin therapy and obesity were associated with an increased incidence of a failed cfDNA test due to low FF. Further research is needed to determine the mechanism by which anticoagulation therapy alters cfDNA test functionality and identify approaches to improve test performance in these women. This article is protected by copyright. All rights reserved.
Casajuana, Josep; Iglesias, Begoña; Fàbregas, Mireia; Fina, Francesc; Vallès, Joan-Antoni; Aragonès, Rosa; Benítez, Mència; Zabaleta, Edurne
Background Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 2003–2004 season. Interventions: intramuscular administration of influenza vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route. Registration number NCT00137579 at clinicaltrials.gov PMID:18507871
Dewilde, Willem J M; Oirbans, Tom; Verheugt, Freek W A; Kelder, Johannes C; De Smet, Bart J G L; Herrman, Jean-Paul; Adriaenssens, Tom; Vrolix, Mathias; Heestermans, Antonius A C M; Vis, Marije M; Tijsen, Jan G P; van 't Hof, Arnoud W; ten Berg, Jurriën M
If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with clopidogrel plus aspirin. We did an open-label, multicentre, randomised, controlled trial in 15 centres in Belgium and the Netherlands. From November, 2008, to November, 2011, adults receiving oral anticoagulants and undergoing PCI were assigned clopidogrel alone (double therapy) or clopidogrel plus aspirin (triple therapy). The primary outcome was any bleeding episode within 1 year of PCI, assessed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769938. 573 patients were enrolled and 1-year data were available for 279 (98·2%) patients assigned double therapy and 284 (98·3%) assigned triple therapy. Mean ages were 70·3 (SD 7·0) years and 69·5 (8·0) years, respectively. Bleeding episodes were seen in 54 (19·4%) patients receiving double therapy and in 126 (44·4%) receiving triple therapy (hazard ratio [HR] 0·36, 95% CI 0·26-0·50, p<0·0001). In the double-therapy group, six (2·2%) patients had multiple bleeding events, compared with 34 (12·0%) in the triple-therapy group. 11 (3·9%) patients receiving double therapy required at least one blood transfusion, compared with 27 (9·5%) patients in the triple-therapy group (odds ratio from Kaplan-Meier curve 0·39, 95% CI 0·17-0·84, p=0·011). Use of clopiogrel without aspirin was associated with a significant reduction in bleeding complications and no increase in the rate of thrombotic events. Antonius Ziekenhuis Foundation, Strect Foundation. Copyright © 2013 Elsevier Ltd. All rights reserved.
A major concern in the management of patients under anticoagulants is the potential for excessive bleeding after dental procedures. Recommendations for the administration of oral anticoagulants in conjunction with oral surgery range from complete withdrawal of anticoagulants to the maintenance of an unchanged therapy. Rising evidences show that the alteration of anticoagulation is not necessary for patients with INR of 4 or less previous to tooth extractions. Topical antifibrinolytics as tranexamic acid control successfully alveolar bleeding. It is time to stop interrupting anticoagulant therapy for oral surgery. A theoretical risk of hemorrhage after dental surgery in patients at therapeutic levels of anticoagulation exists but it is minimal and is greatly overweighed by the risk of thromboembolism after alteration of the anticoagulant therapy.
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
Kent, David M.; Dahabreh, Issa J.; Ruthazer, Robin; Furlan, Anthony J.; Weimar, Christian; Serena, Joaquín; Meier, Bernhard; Mattle, Heinrich P.; Di Angelantonio, Emanuele; Paciaroni, Maurizio; Schuchlenz, Herwig; Homma, Shunichi; Lutz, Jennifer S.; Thaler, David E.
Aims The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). Methods and results Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52–1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44–1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42–0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. Conclusion We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients. PMID:26141397
Bo, Mario; Li Puma, Federica; Badinella Martini, Marco; Falcone, Yolanda; Iacovino, Marina; Grisoglio, Enrica; Menditto, Elena; Fonte, Gianfranco; Brunetti, Enrico; Isaia, Giovanni Carlo; D'Ascenzo, Fabrizio; Gaita, Fiorenzo
Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs. In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF. Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %. After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis. Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.
Kent, David M; Dahabreh, Issa J; Ruthazer, Robin; Furlan, Anthony J; Weimar, Christian; Serena, Joaquín; Meier, Bernhard; Mattle, Heinrich P; Di Angelantonio, Emanuele; Paciaroni, Maurizio; Schuchlenz, Herwig; Homma, Shunichi; Lutz, Jennifer S; Thaler, David E
The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: email@example.com.
D'Angelo, G; Villa, C; Tamborini, A; Villa, S
Our study was designed to evaluate, on healthy subjects and patients on oral anticoagulant therapy vitamin K antagonist (OAT-vka), the possible interference caused by hemolysis on the main coagulation tests. To obtain hemolyzed samples, two methods were used: heat shock and mechanical system. The coagulation tests on hemolyzed samples were performed employing optical automated analyser BCSxp (Siemens Healthcare(®)). Moreover, the prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests were also carried out manually using an electromechanical device (KC4 - Amelung). The PT test, on healthy subjects, in case of moderate hemolysis can be performed without significant interference on automatic instrument. On manual instrument, the PT test can be performed even in case of marked hemolysis. For patients on OAT-vka, the PT test in case of marked hemolysis can be performed both on automatic and manual instrument. For the aPTT test, it can be carried out manually, because also in case of marked hemolysis a statistically significant difference was not observed. For the fibrinogen test, a dramatic concentration decrease was already clear for weak hemolysis. A decreased function on antithrombin test was statistically significant for mild-moderate hemolysis. The D-dimer test showed increased values for mild hemolysis. The rejection of hemolyzed sample and/or the request of a second sample are not always the proper attitudes to take for performing clotting tests. The rational management of the hemolyzed samples decreases the employment of both nursing and technical staff significantly, the turnaround time and, consequently, does not lead to additional costs for each patient involved. © 2015 John Wiley & Sons Ltd.
Staudacher, Dawid L.; Kaiser, Michael; Hehrlein, Christoph; Bode, Christoph; Ahrens, Ingo
Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention. PMID:26439131
The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction undergoing emergent PCI.
Yang, Wu-Xiao; Lai, Chun-Lin; Chen, Fu-Heng; Wang, Ji-Rong; Ji, You-Rui; Wang, Dong-Xia
The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction (AMI) undergoing emergent percutaneous coronary intervention (PCI) was estimated. One hundred and twenty-eight patients were randomly divided into control group and observation group with 64 cases in each group. Control group adopted routine blood coagulation indexes, including prothrombin time, activated partial thromboplastin time, fibrinogen and plasma thrombin time, platelet count and platelet aggregation turbidity analysis; observation group adopted Sonoclot detection technology, including activated clotting time, coagulation rate and platelet function. Anticoagulant therapy selected was of low molecular weight heparin calcium perioperatively, intraoperative unfractionated heparin, and clopidogrel (75 mg) combined with aspirin enteric-coated tablets (100 mg) as antiplatelet drugs. The therapy was administered in accordance with blood coagulation results. The blood coagulation time, postoperative creatine kinase isoenzyme MB, cardiac troponin I and B-type natriuretic peptide levels in the observation group are significantly lower than those in the control group (P<0.05) though the operating time and specifications of the stenting did not show any significant difference (P>0.05). The incidence of recurrent myocardial infarction, microembolism, acute and subacute thrombosis and bleeding events in the observation group are significantly lower than those in the control group (P<0.05). In the control group, there is no difference in the coagulation indexes of the patients with thrombosis events or bleeding events or no event (P>0.05). Whereas, in the observation group, there is significant difference in coagulation indexes of the patients with thrombosis events or bleeding events or no event (P<0.05). In conclusion, Sonoclot detection technology instructs emergent PCI treatment in AMI
Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen
Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722–4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825–5.531, P = 0.118) and 2.003 (95% CI: 0.987–4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430–5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838–5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT
Shi, Quan; Xu, Juan; Zhang, Tong; Zhang, Bin; Liu, Hongchen
Background and Objective: Minor dental surgery is invasive and hemorrhagic. Thus, in patients treated with anticoagulants, the bleeding risk related to these invasive procedures is concerning. The aim of this meta-analysis is to evaluate this risk by comparing the post-operative bleeding rates of oral anticoagulation treatment (OAT) patients (without interrupted or altered anticoagulant intake) with non-OAT patients. Methods: PubMed, Embase and the Cochrane Library were searched for eligible studies that compared the post-operative (following minor dental surgery) bleeding rates of OAT patients without interrupted or altered therapy with those of non-OAT patients. Relative risk (RR) and 95% confidence interval (CI) were calculated. Subgroup analyses were used to identify the association between the bleeding rate and different dental surgeries or anticoagulants. Results: Thirty two full text articles were assessed for eligibility and 20 studies were excluded according to the selection criteria. Finally, 12 studies and a total of 2102 OAT patients and 2271 non-OAT patients were included. A pooled analysis indicated that the post-operative bleeding risk in OAT patients is higher than that of non-OAT patients (RR: 2.794, 95% CI: 1.722-4.532, P = 0.000). The pooled RRs in the dental implant surgery and dental extraction subgroups were 2.136 (95% CI: 0.825-5.531, P = 0.118) and 2.003 (95% CI: 0.987-4.063, P = 0.054), respectively. As for the different oral anticoagulants, the pooled RR in the subgroup of new oral anticoagulants (NOACs) was 1.603 (95% CI: 0.430-5.980, P = 0.482), while the pooled RR in the vitamin K antagonists subgroup was 3.067 (95% CI: 1.838-5.118, P = 0.000). Conclusion: Under current evidence, OAT patients were under a higher post-operative bleeding risk than the non-OAT patients following minor dental surgery. For the dental implant surgeries and dental extractions, our study failed to demonstrate a higher risk of bleeding in the OAT patients
Macdonald, Denis; Bhalla, Pearl; Cass, William; Gollish, Jeff; Brighton, Roger; Gorenstein, Frayda; Vitunjski, Joseph; Ng, Peggy
Objective Evaluation of the safety and potential cost savings of a computerized, laboratory-based program to manage inpatient warfarin thromboprophylaxis after major joint arthroplasty. Design A consecutive-case study of adults. Setting A tertiary care orthopedic institution. Patients Patients requiring joint arthroplasty who had no recent episodes of thromboembolic disease, no mechanical heart valve, atrial fibrillation, severe liver disease or baseline international normalized ratio [INR] greater than 1.3 admitted over a 54-month period (July 1994–December 1998). All patients received a standard regimen of warfarin beginning on the evening after the operation. Four hundred and thirty randomly selected patients managed by the program were followed up by telephone survey 3 months after discharge. Patients exhibiting erratic responses to warfarin were withdrawn from the program and managed individually thereafter. Intervention Major joint arthroplasty with warfarin therapy administered through the computerized program. Main outcome measures Test results maintained within the desired therapeutic range (INR 2.0–3.0), clinically severe bleeding episodes, readmission rates, clinically symptomatic and venographically proven episodes of venous thrombosis or pulmonary embolism. Results Over the study period 5629 patients underwent joint arthroplasty; 5372 patients were considered for the program; 332 patients were ineligible and were managed individually; 311 entered patients did not complete the program. This left 4729 patients who completed the program. In 2932 (62%) patients test results were maintained in the desired therapeutic range. The major bleeding rate was less than 0.5%, the readmission rate was 3.8%, the deep venous thrombosis rate was 3.7% and the pulmonary embolism rate was 0.2% with no thromboembolic related deaths in the small sample cohort. Conclusions The majority of patients requiring warfarin thromboprophylaxis can be safely and effectively managed
Warkentin, Theodore E; Crowther, Mark A
Reversal of pharmacologic anticoagulation is an issue that arises when an anticoagulated patient has major bleeding or when a patient on chronic anticoagulant therapy requires urgent reversal of anticoagulation, for example, for surgery. We reviewed the literature to determine what strategies are available to reverse anticoagulation caused by older agents, such as warfarin or unfractionated heparin (UFH), as well as newer agents, for example, low-molecular-weight heparin, danaparoid, fondaparinux, lepirudin, and argatroban. Specific "antidotes" exist for the "classic" anticoagulant agents: protamine sulfate for UFH, and vitamin K for warfarin. However, vitamin K only begins to reverse warfarin's anticoagulant effect by four to six hours, so urgent situations additionally require blood products, such as plasma (fresh frozen or cryosupermatant plasma), prothrombin complex concentrates, or, possibly, recombinant factor VIIa. A growing problem arises from the increasing use of new anticoagulants that lack specific antidotes. For example, protamine sulfate reverses only about 60% of the anti-factor Xa activity of low-molecular-weight heparin, has negligible effects on danaparoid (a mixture of anticoagulant glycosaminoglycans used to treat heparin-induced thrombocytopenia) and fondaparinux (a novel synthetic antithrombin-binding pentasaccharide with exclusive anti-factor Xa activity approved in the United States for antithrombotic prophylaxis following orthopedic surgery). The new direct thrombin inhibitors (e.g., lepirudin, bivalirudin, argatroban) also have no specific antidote. Newer anticoagulant agents generally lack specific antidotes. Thus, careful choice of an anticoagulant agent and laboratory monitoring where appropriate are needed to minimize risk of bleeding complications.
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
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
Brain, Matthew; Winson, Elizabeth; Roodenburg, Owen; McNeil, John
Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis. A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29(th) February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life. Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical
De Vico, Pasquale; Messino, Valentina; Tartaglione, Alessandra; Beccaris, Camilla; Buonomo, Chiara; Talarico, Daniela; Prati, Paolo; Sabato, Alessandro Fabrizio; Colella, Dionisio Fernando
The study's aim was to examine safety and efficiency of citrate anticoagulated continuous renal replacement therapies (CRRT) in cardiac surgery patients with acute kidney injury and associated liver dysfunction. The study was conducted on critical ICU patients, hospitalized after cardiac surgery, who developed renal and liver acute failures due to low-flow syndrome. CRRT in continuous veno-venous hemodiafiltration with regional citrate anticoagulation (RCA) was prescribed to address renal failure and avoid bleeding-risk. Patient Ca(++) was measured to monitor RCA safety, while thromboelastography (TEG) and circuit Ca(++) were used to verify efficacy. CRRT effectiveness was evaluated through creatinine and urea levels, while liver function was monitored through bilirubin, aspartate aminotransferase, glutamic oxaloacetic transaminase (AST GOT) and gamma glutamyl transferase (GT) levels. The study did not require ethical approval. Hepatic and renal failures were confirmed by baseline levels (total bilirubin=3.1 ± 3.37 mg/dL, AST GOT=153 ± 147 U/L and gamma GT=93.3 ± 86 IU/L, creatinine=1.97 ± 0.88 and blood urea nitrogen [BUN] 98.13 ± 71.34) assessed in 15 patients. During treatment, Ca(++) (patient and circuit) remained stable and within range for the whole therapy thanks to low citrate dose (2.8 ± 0.3 mmol/L of blood), while hepatic markers did not show any significant changes the therapy, although treatment with citrate is contraindicated in patients with hepatic failure. RCA quality was confirmed by TEG values, which showed an anticoagulated circuit with no effects on patients. These results involved a high filter lifespan (49.76 ± 22.10 h) and with an effective creatinine and BUN clearance. No episodes of citrate intoxication were reported (total/ionized calcium ratio remained stable and physiologic). RCA during CRRT with dilute solutions proved both effective and safe, even in patients with acute liver failure.
Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit
PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical
Benoliel, R; Leviner, E; Katz, J; Tzukert, A
Thirty patients taking anticoagulants received routine dental treatment without altering their prothrombin time values. In a follow-up of 5 years, no serious complications were seen in patients with a prothrombin time value of up to 2.5. A protocol is suggested for dental treatment in these patients.
Liao, Li; Shi, Bingzheng; Chang, Heran; Su, Xiaoxia; Zhang, Lichao; Bi, Chunsheng; Shuai, Yi; Du, Xiaoyan; Deng, Zhihong; Jin, Yan
Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure. Histological and homeostasis analysis confirmed that large doses of BMSCs induced disseminated intravascular thrombosis, exhaustion of platelets and coagulation factors, and prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Similar to mouse BMSCs, goat and human BMSCs also induced coagulation reactions in vitro and in vivo. The coagulation was induced mostly by tissue factor, the overexpression of which enhanced the procoagulant activity of BMSCs during in vitro culture. Notably, clinical doses of BMSCs in cell therapy also induced mild and reversible coagulation, which increased BMSC lung embolism and clearance. Anticoagulation treatment by heparin (400 U/kg) prevented BMSC-induced coagulation and the acute adverse effects of large-dose BMSCs infusion efficiently. Importantly, heparin treatment led to decreased BMSC lung embolism and enhanced migration and maintenance of BMSCs to target organs in cell therapy. Based on an experimental colitis model, we confirmed that heparin treatment enhanced the effect of BMSC therapy efficiently to reduce mortality, prevent weight loss, suppress inflammation reaction and alleviate tissue injury. In conclusion, BMSCs possess procoagulant activity that could induce disseminated coagulation and thrombosis in recipients. Anticoagulation treatment by heparin is a practical strategy to improve both the safety and therapeutic effect of BMSC therapy. PMID
Eisenstein, Diana Hill
Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers.
Musielak, Anna; Warzywoda, Alfred; Wojtalik, Michał; Kociński, Bartłomiej; Kroll, Paweł; Ostalska-Nowicka, Danuta; Zachwieja, Jacek
Patients after a cardiac surgery in cardiopulmonary bypass often present an acute kidney failure. Continuous renal replacement therapy (CRRT) is often required. The aim of this study was to present effectiveness and safety of CRRT with regional citrate anticoagulation (RCA-CRRT) in small children after cardiac surgery. A retrospective analysis was conducted on 15 patients after cardiac surgery and who had RCA-CRRT performed in 2014. The established protocol was followed. Mean time on the RCA-CRRT was 192 h 40 min with the circuit mean lifetime of 43 h 33 min. Clotting was found to be a cause of shutdown in 29% of circuits. No severe electrolyte and metabolic disorders were observed. The RCA-CRRT is a safe procedure for critically ill children with contraindications to the CRRT with heparin anticoagulation. To avoid adverse effects related to metabolic disorders a proper procedure protocol has to be followed. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.
Oral anticoagulant therapy for stroke prevention in patients with atrial fibrillation undergoing ablation: results from the First European Snapshot Survey on Procedural Routines for Atrial Fibrillation Ablation (ESS-PRAFA).
Potpara, Tatjana S; Larsen, Torben B; Deharo, Jean Claude; Rossvoll, Ole; Dagres, Nikolaos; Todd, Derick; Pison, Laurent; Proclemer, Alessandro; Purefellner, Helmut; Blomström-Lundqvist, Carina
The European Snapshot Survey on Procedural Routines in Atrial Fibrillation Ablation (ESS-PRAFA) is a prospective, multicentre snapshot survey of patients undergoing atrial fibrillation (AF) ablation, conducted to collect patient-based data on current clinical practices in AF ablation in context of the latest AF Guidelines and contemporary oral anticoagulant therapies. The EP Research Network Centres were asked to prospectively enrol consecutive patients during a 6-week period (September/October 2014). Data were collected via the web-based case report form. We present the results pertinent to the use of antithrombotic therapies. Thirteen countries prospectively enrolled 455 eligible consecutive patients [mean age 59 ± 10.8 years, 131 (28.8%) females]. The mean CHA2DS2-VASc score was 1.12 ± 1.06 [137 patients (30.1%) had a score of ≥2]. Before ablation, 443 patients (97.4%) were on anticoagulant therapy [143 (31.4%) on non-vitamin K antagonist oral anticoagulants (NOACs) and 264 (58.0%) on vitamin K antagonists (VKAs)]. Of the latter, 79.7% underwent ablation without VKA interruption, whilst a variety of strategies were used in patients taking NOAC. After ablation, most patients (89.3%) continued the same anticoagulant as before, and 2 (0.4%) were not prescribed any anticoagulation. At discharge, 280 patients (62.2%) were advised oral anticoagulation for a limited period of mean 3.8 ± 2.2 months. On multivariate analysis, CHA2DS2-VASc, AF duration, prior VKA use, and estimated AF ablation success were significantly associated with the decision on short-term anticoagulation. Our results show the increasing use of NOAC in patients undergoing AF ablation and emphasize the need for more information to guide the periprocedural use of both NOACs and VKAs in real-world setting.
Age-related prevalence of diabetes mellitus, cardiovascular disease and anticoagulation therapy use in a urolithiasis population and their effect on outcomes: the Clinical Research Office of the Endourological Society Ureteroscopy Global Study.
Daels, F Pedro J; Gaizauskas, Andrius; Rioja, Jorge; Varshney, Anil K; Erkan, Erkan; Ozgok, Yasar; Melekos, Michael; de la Rosette, Jean J M C H
This study examined the prevalence of risk factors for urological stone surgery and their possible influence on outcome and complications following ureteroscopy (URS). The Clinical Research Office of the Endourological Society Ureteroscopy Global Study collected prospective data on consecutive patients with urinary stones treated with URS at centers around the world for 1 year. The prevalence of common comorbidities and anticoagulation therapy and their relationship with complications and age were examined. Of 11,719 patients, 2,989 patients (25.8%) had cardiovascular disease, including 22.6% with hypertension, and 1,266 patients (10.9%) had diabetes mellitus. Approximately six percent of patients were receiving oral anticoagulation therapy, including aspirin (3.7%) and clopidogrel (0.8%). The prevalence of hypertension and diabetes mellitus and the proportion of patients receiving anticoagulant medication and/or antidiabetes treatment increased with age. Elderly were more likely to develop a postoperative complication when they had diabetes, a cardiovascular disease or received anticoagulation therapy. Post-operative bleeding was higher in patients receiving anticoagulants than those not receiving them (1.1 vs. 0.4%; p < 0.01). Patients with risk factors for stone formation had more complications than those without (4.9 vs. 3.0%, p < 0.001). This is the first study confirming in a global population that URS can effectively and safely be performed in a population with high comorbidity. The risk of a complication was highest among elderly patients presenting with comorbidities.
Verdecchia, Paolo; Reboldi, Gianpaolo; Di Pasquale, Giuseppe; Mazzotta, Giovanni; Ambrosio, Giuseppe; Yang, Sean; Pogue, Janice; Wallentin, Lars; Ezekowitz, Michael D; Connolly, Stuart J; Yusuf, Salim
It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF. Copyright © 2014 Elsevier Inc. All rights reserved.
Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine
Background Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. Objective The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. Methods We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. Results The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of m
Lee, Jung-Ah; Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine
Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of mHealth technology may be helpful for medication
Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association.
Hernández Madrid, Antonio; Potpara, Tatjana S; Dagres, Nikolaos; Chen, Jian; Larsen, Torben B; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Sciaraffia, Elena; Proclemer, Alessandro; Cheggour, Saida; Amara, Walid; Blomstrom-Lundqvist, Carina
The purpose of this patient survey was to analyse the knowledge about blood thinning medications relative to gender, age, education, and region of residence in patients with atrial fibrillation (AF). A total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from eight European countries responded to this survey. Most patients understood that the indication for anticoagulation therapy was to 'thin the blood', but 8.1% responded that the purpose of the medication was to treat the arrhythmia. Patients with college or university grades reported less frequent deviations from their target INR range compared with those without schooling (2.8% vs. 5.1%, P < 0.05). The awareness of anticoagulation-related risk of bleedings was lowest in patients without schooling (38.5%) and highest in those with college and university education (57.0%), P < 0.05. The same pattern was also observed regarding patient's awareness of non-vitamin K antagonist oral anticoagulants (NOACs): 56.5% of the patients with university education and only 20.5% of those without schooling (P < 0.05) knew about NOACs, indicating that information about new anticoagulation therapies remains well below the target. Bleeding events were statistically less frequent in patients on NOACs compared with vitamin K antagonists. The education level and patients' knowledge have a direct influence on the global management of the anticoagulation.
Alonso Roca, Rafael; Figueroa Guerrero, Carmen Arlene; Mainar de Paz, Victoria; Arribas García, M Paz; Sánchez Perruca, Luis; Rodríguez Barrientos, Ricardo; Casado López, Mariano; Pedraza Flechas, Ana M
To determine quality control of patients with oral anticoagulant treatment recruited in Primary Care (PC) using the Rosendaal method to estimate time in therapeutic range (TTR) and comparing it with fraction of international normalized ratio (INR) in range and cross-sectional analysis (last INR registred). A retrospective observational study based on electronic medical record in routine clinical practice. PC centers (262) in Madrid. We included all patients with acenocumarol treatment, with an INR therapeutic range established between 2 and 3. We excluded patients with valvular pathology and disrupted clinical follow up in PC (<3 INR determinations in the studied period, a period of>90 days or ≥ 3 periods of>60 days between 2 determinations). The final population was 49,312 patients. The variables considered were all INR values and their respective dates. TTR was calculated by the 3 methods above mentioned. We considered "therapeutic range" INR between 2-3 and "adjusted range" INR between 1.8-3.2. Optimal control for each patient was considered TTR>60%. By using Rosendaal method, TTR was 66.8% (81.7% adjusted), with a percentage of total INR in range was 58.8% (66.5% adjusted), and, with the cross-sectional analysis, it was 70.5% (76.8% adjusted). Mean TTR was 65% (standard deviation 20.3), and the percentage of patients with TTR>60% was 63.3% (88.1% adjusted). The quality control of patients with oral anticoagulants in PC in Madrid is acceptable, similar or higher to other studies and pivotal trials of new anticoagulants. Compared to the Rosendaal method, total fraction of INR underestimates quality control, and cross-sectional analysis slightly overestimates it. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.
Ball, J H
An understanding of the primary mechanisms of hemostasis, including the coagulation pathways and the intrinsic, extrinsic, and common systems, is the basis for treating the anticoagulated patient. Two major anticoagulants are used for treating those who may be at risk for thromboembolic crisis. These drugs include Coumadin, which is an oral anticoagulant, and heparin, a parenteral anticoagulant, which is often used for acute thromboembolic episodes or for hospitalization protocols that include significant surgical procedures. The practitioner should be familiar with common dental drugs that can interact with anticoagulants and should consult with the patient's physician before administering any such drugs. By placing the patient into one of three dental treatment categories, appropriate anticoagulation therapy can be rendered to each patient according to his or her needs. Low-risk procedures require no change in anticoagulation medication. For moderate-risk procedures, withdrawal of anticoagulation medication 2 days before the procedure and verified with the PT the day of the procedure is indicated. For high-risk dental procedures, using a heparin protocol should be strongly considered. In all instances of dental treatment, the oral tissues should be treated atraumatically using local hemostatic measures for control of hemorrhage. Treating medically compromised patients who are on a variety of medications is becoming more common in dentistry today. Understanding the underlying disease and the appropriate protocol for treatment of anticoagulated patients reduces the risk of thromboembolism and hemorrhagic complications.
Ageno, Walter; Mantovani, Lorenzo G; Haas, Sylvia; Kreutz, Reinhold; Haupt, Verena; Schneider, Jonas; Turpie, Alexander Gg
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism, poses a substantial clinical risk, and the incidence of these thrombotic-related diseases remains high. Anticoagulation aims to prevent thrombus extension and reduce the risk of recurrent events, particularly fatal pulmonary embolism. In EINSTEIN DVT, rivaroxaban was non-inferior to enoxaparin/vitamin K antagonists for the reduction of recurrent VTE, with a similar safety profile and a net clinical benefit. EINSTEIN EXT investigated patients receiving long-term treatment in whom there was no clear decision about continuing or stopping anticoagulation; rivaroxaban was superior to placebo in the reduction of recurrent VTE, showing an acceptable benefit-risk balance. Rivaroxaban has the potential to replace standard therapy, usually parenteral low molecular weight heparin overlapping with and followed by a vitamin K antagonist, for the treatment of acute symptomatic DVT and the secondary prevention of VTE. As the use of rivaroxaban for DVT treatment increases in clinical practice, a fundamental understanding of its clinical benefits in everyday patient care is essential. XALIA (XArelto for Long-term and Initial Anticoagulation in venous thromboembolism) is a multicentre, prospective, non-interventional, observational study investigating the effectiveness and safety of a single-drug approach with rivaroxaban compared with standard therapy in patients with DVT. The study cohort will include approximately 4800 patients (≥18 years old) with objectively confirmed acute DVT who will be treated for a period of ≥3 months. The primary outcomes will be the incidence of treatment-emergent adverse events (primarily major bleeding), symptomatic recurrent venous thromboembolic events and all-cause mortality. Secondary outcomes include: major cardiovascular events; patient-reported treatment satisfaction and adherence; healthcare resource utilization; reasons for drug switching or
Kumar, K.R. Ashok; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha
Introduction Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. Aim The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. Materials and Methods A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. Results All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1st and 3rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1st and 3rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1st and 3rd post-operative days (p <0.0001). Conclusion The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls. PMID:27790577
Kumar, K R Ashok; Kumar, Jambukeshwar; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha
Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1(st) and 3(rd) day respectively) was significantly lower than the control sites (4.0,1.87 on 1(st) and 3(rd) day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1(st) and 3(rd) post-operative days (p <0.0001). The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls.
António, Natália; Castro, Graça; Ramos, Domingos; Machado, António; Gonçalves, Lino; Macedo, Tice; Providência, Luís A
The management of patients taking long-term oral anticoagulants who require dental surgery is still highly controversial. The risk of bleeding associated with dental treatment under oral anticoagulants must be weighed against the risk of thromboembolism associated with suspension of antithrombotic therapy. Mortality and morbidity associated with thromboembolic events are higher than those associated with hemorrhagic events after minor oral surgery procedures. Evidence-based information does not support oral anticoagulant suspension before minor oral surgery. The authors propose a management protocol for chronically anticoagulated patients who require a dental procedure, to reduce both thromboembolic risk and the risk of bleeding.
Barnes, Geoffrey D; Kline-Rogers, Eva
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.
Barnes, Geoffrey D.; Kline-Rogers, Eva
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
Anticoagulation is vital for stroke and systemic embolism prevention in patients with atrial fibrillation. Current therapy with the vitamin K inhibitor warfarin has many inherent limitations in clinical practice. With the potential of broadening anticoagulation therapy to a larger population, new classes of anticoagulants have recently emerged with the potential for improved efficacy, safety and convenience. Direct thrombin inhibitor and Factor Xa inhibitor classes are showing promise for both patients and clinicians. PMID:23251767
Plesch, W; van den Besselaar, A M H P
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.
Gómez-Outes, Antonio; Suárez-Gea, Maria Luisa; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Vargas-Castrillón, Emilio
The therapeutic armamentarium of parenteral anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux, recombinant hirudins (i.e. bivalirudin, desirudin, lepirudin) and argatroban. These drugs are effective and safe for prevention and/or treatment of thromboembolic diseases but they have some drawbacks. Among other inconveniences, UFH requires regular anticoagulant monitoring as a result of variability in the anticoagulant response and there is a risk of serious heparin-induced thrombocytopaenia (HIT). LMWH, fondaparinux and recombinant hirudins are mainly cleared through the kidneys and their use in patients with severe renal insufficiency may be problematic. LMWH is only partially neutralized by protamine while fondaparinux and recombinant hirudins have no specific antidote. Novel anticoagulants in development for parenteral administration include new indirect activated factor Xa (FXa) inhibitors (idrabiotaparinux, ultra-low-molecular-weight heparins [semuloparin, RO-14], new LMWH [M118]), direct FXa inhibitors (otamixaban), direct FIIa inhibitors (flovagatran sodium, pegmusirudin, NU172, HD1-22), direct FXIa inhibitors (BMS-262084, antisense oligonucleotides targeting FXIa, clavatadine), direct FIXa inhibitors (RB-006), FVIIIa inhibitors (TB-402), FVIIa/tissue factor inhibitors (tifacogin, NAPc2, PCI-27483, BMS-593214), FVa inhibitors (drotrecogin alpha activated, ART-123) and dual thrombin/FXa inhibitors (EP217609, tanogitran). These new compounds have the potential to complement established parenteral anticoagulants. In the present review, we discuss the pharmacology of new parenteral anticoagulants, the results of clinical studies, the newly planned or ongoing clinical trials with these compounds, and their potential advantages and drawbacks over existing therapies.
Pasin, Laura; Frati, Elena; Cabrini, Luca; Landoni, Giovanni; Nardelli, Pasquale; Bove, Tiziana; Calabrò, Maria Grazia; Scandroglio, Anna Mara; Pappalardo, Federico; Zangrillo, Alberto
Aims: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. Settings and Design: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). Materials and Methods: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. Results: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. Conclusions: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings. PMID:26139737
Netsch, Christopher; Stoehrer, M; Brüning, M; Gabuev, A; Bach, T; Herrmann, T R W; Gross, A J
To evaluate the safety and efficacy of Thulium VapoEnucleation of the prostate (ThuVEP) for patients on oral anticoagulants (OA) with symptomatic benign prostatic obstruction (BPO). Fifty-six patients, undergoing ThuVEP at two institutions, were evaluated from May 2009 until June 2011. All patients were at high cardiopulmonary risk and presented with a median American Society of Anesthesiology score of 3 [interquartile range (IQR) 2-3]. Thirty-two patients were on aspirin, 8 were on clopidogrel or clopidogrel and aspirin, and 16 on phenprocoumon at the time of surgery. Patient demographic, perioperative, and follow-up data were analyzed. Median prostate volume was 50 (IQR 34-76) cc, and resected tissue weight was 32 (IQR 20-50) g. The median operative time was 61.5 (IQR 40-100.75) min, and the catheter time 2 (IQR 2-3) days. There were no perioperative thromboembolic events. Five patients (8.9%) required a second-look operation in the immediate postoperative course (hemorrhage n = 4, residual adenoma n = 1) and four (7.1%) blood transfusions. Complications within the first 30 days included urinary tract infections (1.7%), urinary retention (3.6%), and delayed bleeding (7.1%). These complications were managed conservatively. At 12-month follow-up, median QoL [5 (IQR 3.75-5) vs. 1 (IQR 1-2)], IPSS [21.5 (IQR 15.5-23.75) vs. 5 (IQR 3-8)], Qmax [7.7 (IQR 6.3-10) vs. 28.3 (IQR 21.25-39.2) ml/s], and postvoiding residual urine [100 (IQR 46-200) vs. 17.5 (IQR 0-36) ml] improved significantly (p < 0.002). Thulium VapoEnucleation of the prostate seems to be a safe and efficacious procedure for the treatment of symptomatic BPO in patients at high cardiopulmonary risk on OA.
Shapiro, Nancy L; Durr, Emily A; Krueger, Courtney D
A 32-year-old, morbidly obese African-American woman developed bilateral pulmonary emboli 12 days after undergoing Roux-en-Y gastric bypass surgery. Three days later, after receiving heparin and warfarin, she developed heparin-induced thrombocytopenia type II (HIT-II). An argatroban 1.5-microg/kg/minute infusion was administered for approximately 2.5 days. The patient also received four doses of warfarin, totaling 37.5 mg. The argatroban infusion was discontinued early on hospital day 6, at which time the patient's international normalized ratio (INR) was 4.36 and activated partial thromboplastin time (aPTT) 85.9 seconds. Her INR and aPTT values continued to rise after the argatroban was discontinued and peaked 3 days later at 5.28 and 123.6 seconds, respectively. At this time her platelet count had improved from 139 x 10(3)/mm(3) to 543 x 10(3)/mm(3). No additional warfarin was administered before discharge. On hospital day 11, the patient was discharged home with an INR of 4.12 and an aPTT of 67.1 seconds. Her aPTT and INR values remained elevated for 19 days after receiving her last dose of warfarin and for 20 days after argatroban discontinuation. She experienced no bleeding complications from these supratherapeutic coagulation parameters. She resumed treatment with warfarin as an outpatient and completed a 6-month course of anticoagulation without further incident. Clinicians should be aware that coagulation parameters may remain elevated longer than expected after argatroban discontinuation in certain patients taking concomitant warfarin. Patients with liver dysfunction and obesity appear most likely to be affected.
Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies.
Bavishi, Chirag; Koulova, Anna; Bangalore, Sripal; Sawant, Ashwin; Chatterjee, Saurav; Ather, Sameer; Valencia, Jose; Sarafoff, Nikolaus; Rubboli, Andrea; Airaksinen, Juhani K; Lip, Gregory Y H; Tamis-Holland, Jacqueline E
To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
Akram, Muhammad; Rashid, Abid
Medicinal plants have been used for treatment of human ailments since ancient times. Objective of this study is to document the effect of herbal drugs on anticoagulant therapy. The material for this review was taken mostly from PubMed and the Cochrane database of systematic reviews. Some other relevant references were collected from personal database of papers on anti-coagulant properties of plants. Literature review shows that many plants such as Thymus vulgaris, Cyamopsis tetragonoloba taub, Pulmonaria officinalis and Cinnamomum cassia etc have anti-coagulant activity. This review shows that medicinal plants should be prescribed with care to patients on anticoagulant therapy.
Wolkanin-Bartnik, Jolanta; Pogorzelska, Hanna; Szperl, Małgorzata; Bartnik, Aleksandra; Koziarek, Jacek; Bilinska, Zofia T
Despite the recent emergence of new oral anticoagulants, vitamin K antagonists remain the primary therapy in patients with atrial fibrillation and the only therapy licensed for use in patients with artificial heart valves. The aim of this study was (a) to assess the impact of clinical and genetic factors on acenocoumarol (AC) dose requirements and the percentage of time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC dose calculation algorithm. We included 235 outpatients of the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC for artificial heart valves and/or atrial fibrillation. A multiple linear-regression analysis was performed using log-transformed effective AC dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other clinical factors as independent predictors. We identified factors that influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035), body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic factors explained 49.0% of AC dose variability. We developed a dosing calculation algorithm that is, to the best of our knowledge, the first one to assess the effect of such clinical factors as creatinine clearance and dietary vitamin K intake on the AC dose. The clinical usefulness of the algorithm was assessed on separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake higher than 200 mcg/day improved international normalized ratio control (%TTR 73.3±17 vs. 67.7±18, respectively, P=0.04). Inclusion of a variety of genetic and clinical factors in the dosing calculation algorithm allows for precise AC dose estimation in most patients and thus improves the efficacy and safety of the therapy.
Heit, J A
Common indications for chronic anticoagulation include mechanical prosthetic heart valve, non-rheumatic atrial fibrillation, and venous thromboembolism. Perioperative management of the chronically anticoagulated patient is a complex medical problem, and includes the following issues: urgency of surgery, risk of thromboembolism in the absence of anticoagulation, bleeding risk, consequences of bleeding, ability to control bleeding physically, and duration of bleeding risk after the procedure. Most patients can be managed safely by stopping oral anticoagulants 4-5 days before surgery and restarting anticoagulation after the procedure at the patient's usual daily dose. In general, dental procedures and cataract extraction can be performed without interrupting anticoagulation. Most other procedures can be safely performed with an INR < or = 1.4. For patients with double-wing prosthetic valves (e.g., St. Jude, Carbomedics) in the aortic position, uncomplicated atrial fibrillation, or a remote (>3 months) history of venous thromboembolism, oral anticoagulants can be stopped 4-5 days before surgery and restarted at the usual daily dose immediately after surgery. For other patients at higher risk of thrombosis, "bridging therapy" with outpatient low molecular weight heparin is safe and effective. For urgent procedures, a small dose of oral vitamin K usually will reduce the INR within 24-36 hours to a level sufficient for surgery and avoids exposure to transfused blood products.
Koyama, Yasushi; Suzuki, Yasuo
A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy. PMID:27672472
Salvador, Carlos H; Ruiz-Sanchez, Antonio; González de Mingo, Miguel A; Carmona Rodríguez, Montserrat; Carrasco, Mario Pascual; Sagredo, Pilar G; Fragua, Juan A; Caballero-Martinez, Fernando; García-López, Fernando; Márquez-Montes, Joaqu N; Monteagudo, José L
The authors have designed and developed a telemedicine-based service for the follow-up and monitoring of patients on oral anticoagulant therapy (OAT) that consists of two phases; the first involving self-testing and the second involving guided self-management. To evaluate the first phase of the protocol, a project was conducted with 108 patients, with a mean age of 72.7 years and a mean treatment time at the start of the study of 55.2 months, divided into two groups: telemedicine and control (conventional procedure). The degree of anticoagulation control was similar in the two groups: individual in-range international normalized ratios (59.2% vs 61.1%; p = 0.55) and individual time within target range (65.7% vs 66.4%; p = 0.85) showed no significant differences. The incidence of adverse events--death (5.5% vs 5.5%; p = 1.0), major hemorrhagic complications (0% vs 1.8%; p = 1.0), minor hemorrhagic complications (7.4% vs 3.7%; p = 0.67), and thromboembolism (1.8% vs 3.7%; p = 1.0)--was also similar, with no significant differences. Acceptability of the change, measured in terms of quality of life (SF-12 and Sawicki questionnaires) and anxiety (state-trait anxiety inventory questionnaire) at the beginning and end of the study period was higher in the telemedicine group, with statistically significant improvements in mental component summary (3.6 vs -6.2; p = 0.02), dissatisfaction (-0.8 vs 0.2; p = 0.001), stress (-0.3 vs 0.05; p = 0.03), limitations (-0.2 vs 0.3; p = 0.005), social problems (-0.1 vs 0.3; p = 0.03), and state anxiety (-2.5 vs 2.3; p = 0.04). Parameters related to costs, such as the mean number per patient of office visits due to OAT (1.7 vs 13.8; p < 0.001) and other office visits (10.1 vs 11.5; p = 0.028), were also more favorable in the telemedicine group, as were additional parameters that enabled an exhaustive evaluation of the service. The positive results obtained indicate that the second phase of the trial can be initiated.
Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.
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.
Purcell, C A
Most anticoagulated patients can be safely managed for routine dental treatment in the outpatient setting by following appropriate guidelines. Management should be based on the present level of anticoagulation as assessed by tests, in particular the international normalised ratio (INR), which should be carried out as close to the intervention as possible. A philosophy of minimal, if any, alteration to the level of anticoagulation should be adopted. This is particularly true for procedures producing minimal bleeding such as scaling and cleaning which, in the past, have resulted in patients having their INR lowered, with its attendant risks. The patient's anticoagulation is potentially life-saving and, where at all possible, should be maintained at therapeutic levels when therapy for non-threatening conditions is planned.
Salmerón Febres, Luis Miguel; Cuenca Manteca, Jorge
Anticoagulation is the treatment of choice in the management of venous thromboembolic disease. This approach is applied to reduce mortality and the risk of recurrences and associated complications. Standard therapy for non-oncologic patients has traditionally been based on parenteral anticoagulation followed by vitamin K antagonists. However, this approach has many limitations. The aim of this manuscript was to critically review current evidence on the use of direct oral anticoagulants in the treatment of venous thromboembolic disease by analyzing the specific characteristics of each drug. Direct oral anticoagulants have many advantages over standard therapy. While they are equally effective as standard therapy for reducing the possibility of recurrence of venous thromboembolic disease, they carry a lower risk of major bleeding. Direct oral anticoagulants are an attractive alternative to standard therapy for the treatment of venous thromboembolism. Copyright © 2017 Elsevier Inc. All rights reserved.
The effect of varying levels of dietary vitamin K intake on therapeutic International Normalized Ratio (INR) values among patients starting warfarin therapy has not been well studied. We performed a prospective cohort study among 282 patients to explore the independent associations between usual in...
Background Despite the existing evidence that highlights the benefits of oral anticoagulation therapy (OAT) self-testing and self-management by patients in comparison with conventional control, significant progress is still needed in the implementation of computer-based, Internet-assisted systems for OAT within health care centers. The telecontrol tool “SintromacWeb” is a previously validated system for OAT management at home, which is currently operative and accessed by patients through a hospital Web portal. Objective The intent of the study was to assess the effectiveness and safety of OAT management in patients using the SintromacWeb telecontrol system in reference to control in patients using the conventional system (management at the hematology department), in terms of time in therapeutic range (TTR) of International Normalized Ratio (INR). Methods In this observational prospective study, patients were identified by their physician and divided in two groups according to the OAT management system that they were already using (conventional control or telecontrol with SintromacWeb). For 6 months, patients were required to visit the hematology department every time their physician considered it necessary according to usual clinical practice. Sociodemographic and clinical variables for the study were collected at first visit (baseline) and at those visits closest to 2, 4, and 6 months after first visit. Results A total of 173 patients were evaluated, 87 with conventional control and 86 with telecontrol. Follow-up time was a median of 6.3 (range 5.2-8.1) months. The average time of OAT treatment prior to enrollment was 9.2 (SD 6.4) years. Patients in the telecontrol group tested their INR a median of 21 (range 4-22) days versus a median of 35 (range 14-45) days in patients in the conventional control group (P<.001). TTR in the telecontrol group was 107 (SD 37) days versus 94 (SD 37) days in the conventional control group (an increase of 12.6%; P=.02). In all
Riess, H; Loew, A; Himmelreich, G
Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.
Stavrakis, Stavros; Stoner, Julie A; Kardokus, Joel; Garabelli, Paul J; Po, Sunny S; Lazzara, Ralph
We hypothesized that intermittent anticoagulation based on daily rhythm monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among patients with paroxysmal atrial fibrillation (AF). Patients with paroxysmal AF and ≥1 risk factors for stroke were randomized to either intermittent or continuous anticoagulation. Those in the intermittent group were instructed to transmit a daily ECG using an iPhone-based rhythm monitoring device. If AF was detected, patients received one of the NOACs for 48 h-1 week. Patients who failed to transmit an ECG for three consecutive days or more than 7 days total were crossed over to continuous anticoagulation. Patients in the continuous group received one of the NOACs. Fifty-eight patients were randomized to either intermittent (n = 29) or continuous anticoagulation (n = 29). Over a median follow-up of 20 months, 20 patients in the intermittent group failed to submit a daily ECG at least once (median three failed submissions). Four patients (14 %) crossed over to continuous anticoagulation due to failure to submit an ECG for three consecutive days. One stroke (continuous group) occurred during the study. Major bleeding occurred in two patients in the continuous and one patient in the intermittent group, after crossing over to continuous anticoagulation. In a prespecified per-protocol analysis, gastrointestinal bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047). Intermittent anticoagulation based on daily rhythm monitoring is feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A larger trial, adequately powered to detect clinical outcomes, is warranted.
Hammar, Samuel P
We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto(®) (rivaroxaban).
Hammar, Samuel P.
We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban). PMID:26236607
Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils
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
Llau, Juan V; Ferrandis, Raquel; López Forte, Cristina
Among the drugs most widely consumed by patients are both antiplatelet agents (aspirin, clopidogrel, ticlopidine) and anticoagulants (acenocoumarol, warfarin, low molecular weight heparin, fondaparinux). The use of these drugs in the perioperative period is an essential concern in patient care due to the need to balance the risk of bleeding against thrombotic risk (arterial or venous), which is increased in surgical patients. The present review highlights three main aspects. Firstly, withdrawal of antiplatelet agents is recommended between 1 week and 10 days before surgery to minimize perioperative bleeding. However, this practice has been questioned because patients without the required antiplatelet coverage may be at greater risk of developing cardiac, cerebral or peripheral vascular complications. Therefore, the recommendation of systematic antiplatelet withdrawal for a specific period should be rejected. Currently, risks should be evaluated on an individual basis to minimize the time during which the patient remains without adequate antiplatelet protection. Secondly, thromboprophylaxis is required in most surgical patients due to the high prevalence of venous thromboembolic disease. This implies the use of anticoagulants and the practice of regional anesthesia has been questioned in these patients. However, with the safety recommendations established by the various scientific societies, this practice has been demonstrated to be safe. Finally, "bridge therapy" in patients anticoagulated with acenocoumarol should be performed on an individual basis rather than systematically without taking into account the thrombotic risks of each patient. The perioperative period involves high arterial and venous thrombotic risk and the optimal use of antiplatelet agents and anticoagulants should be a priority to minimize this risk without increasing hemorrhagic risk. Multidisciplinary consensus is essential on this matter.
Khan, Tayyaba Irfan; Kamali, Farhad; Kesteven, Patrick; Avery, Peter; Wynne, Hilary
Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0.5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self-monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61.1 vs. 70.4; mean difference 8.8; 95% confidence interval (CI): -0.2-17.8; P = 0.054] and following education and self-monitoring (57 vs. 71.1; mean difference 14.1; 95% CI: 6.7-21.5; P < 0.001), compared with those patients following usual clinic care (60.0 vs. 63.2; mean difference 3.2; 95% CI: -7.3-13.7). Using the same comparative periods, the INR SD fell by 0.24 (P < 0.0001) in the group allocated to education and self-monitoring, 0.26 (P < 0.0001) in the group receiving education alone and 0.16 (P = 0.003) in the control group. Inter-group differences were not statistically significant (intervention groups 0.26 +/- 0.30 vs. control 0.16 +/- 0.3, P = 0.10). Quality-of-life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self-monitoring. Patient education regarding anticoagulation therapy could be a cost-effective initiative and is worthy of further study.
How, Choon How
Anticoagulation therapy is effective in preventing primary and secondary thromboembolic events due to atrial fibrillation. Warfarin, which was approved by the United States in 1954, was the only long-term oral anticoagulation therapy till the approval of dabigatran in 2010, and of rivaroxaban and other direct factor Xa inhibitors from 2011, forming a group known as novel oral anticoagulants (NOAC). NOAC have fewer food and drug interactions compared to warfarin; hence, the patient will require fewer clinic visits. However, the short half-life of NOAC means that twice-a-day dosing is needed and there is higher risk of a prothrombotic state when doses are missed. Other disadvantages are the lack of long-term data on NOAC, their high cost and the current lack of locally available antidotes. PMID:26702159
Guimarães, Patrícia O; Wojdyla, Daniel M; Alexander, John H; Thomas, Laine; Alings, Marco; Flaker, Greg C; Al-Khatib, Sana M; Hanna, Michael; Horowitz, John D; Wallentin, Lars; Granger, Christopher B; Lopes, Renato D
Evidence supporting use of antithrombotic therapy in atrial fibrillation (AF) is based mainly on data from patients with permanent, persistent, or paroxysmal AF. Less is known about the risk following a new diagnosis of AF and the efficacy and safety of apixaban in these patients. Using data from ARISTOTLE, we assessed the relationship between timing of AF diagnosis and clinical outcomes and the efficacy and safety of apixaban versus warfarin in these patients. Recently diagnosed AF was defined as a new diagnosis of AF within 30days prior to enrollment. Cox proportional hazards models were used to determine the association between recently diagnosed AF and clinical outcomes. We also assessed the efficacy and safety of apixaban versus warfarin according to time since AF diagnosis. In ARISTOTLE, 1899 (10.5%) patients had recently diagnosed AF. After adjustment, patients with recently versus remotely diagnosed AF had a similar risk of stroke/systemic embolism (HR=1.07, 95% CI=0.80-1.42; p=0.67), but higher mortality was seen in patients with recently diagnosed AF (adjusted HR=1.21, 95% CI=1.02-1.43; p=0.03). The beneficial effects of apixaban, compared with warfarin, on clinical outcomes were consistent, irrespective of timing of AF diagnosis (all interaction p-values >0.12). Patients with recently diagnosed AF had a similar risk of stroke but higher mortality than patients with remotely diagnosed AF, suggesting that they are not at "low risk" and warrant stroke prevention strategies. The benefits of apixaban over warfarin were preserved, irrespective of timing of AF diagnosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Chaudhary, Nabin; Bundhun, Pravesh Kumar; Yan, He
Abstract Background: Data regarding the clinical outcomes in patients with atrial fibrillation (AF) receiving dual antiplatelet therapy (DAPT) and an anticoagulant in addition to DAPT (DAPT + vitamin K antagonist [VKA]) after coronary stent implantation are still controversial. Therefore, in order to solve this issue, we aim to compare the adverse clinical outcomes in AF patients receiving DAPT and DAPT + VKA after percutaneous coronary intervention and stenting (PCI-S). Methods: Observational studies comparing the adverse clinical outcomes such as major bleeding, major adverse cardiovascular events, stroke, myocardial infarction, all-cause mortality, and stent thrombosis (ST) in AF patients receiving DAPT + VKA therapy, and DAPT after PCI-S have been searched from Medline, EMBASE, and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables, and the pooled analyses were performed with RevMan 5.3. Results: Eighteen studies consisting of a total of 20,456 patients with AF (7203 patients received DAPT + VKA and 13,253 patients received DAPT after PCI-S) were included in this meta-analysis. At a mean follow-up period of 15 months, the risk of major bleeding was significantly higher in DAPT + VKA group, with OR 0.62 (95% CI 0.50–0.77, P < 0.0001). There was no significant differences in myocardial infarction and major adverse cardiovascular event between DAPT + VKA and DAPT, with OR 1.27 (95% CI 0.92–1.77, P = 0.15) and OR 1.17 (95% CI 0.99–1.39, P = 0.07), respectively. However, the ST, stroke, and all-cause mortality were significantly lower in the DAPT + VKA group, with OR 1.98 (95% CI 1.03–3.81, P = 0.04), 1.59 (95% CI 1.08–2.34, P = 0.02), and 1.41 (95% CI 1.03–1.94, P = 0.03), respectively. Conclusion: At a mean follow-up period of 15 months, DAPT + VKA was associated with significantly lower risk of stroke, ST, and
Mirolovics, Ágnes; Papp, Csaba; Zsuga, Judit; Bereczki, Dániel
The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren't within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa-factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications.
Early and late effects of coumarin therapy started before percutaneous coronary intervention: Clinical, angiographic and cost-effective outcome of the Balloon Angioplasty and Anticoagulation Study (BAAS).
Ten Berg, J M; Kelder, J C; Suttorp, M J; Mast, E G; Bal, E T; Ernst, J M P G; Plokker, H W M
Coronary angioplasty frequently creates a thrombogenic surface with subsequent mural thrombosis that may lead to acute complications and possibly stimulates the development of restenosis. Whether coumarins can prevent these complications is unclear. In the Balloon Angioplasty and Anticoagulation Study (BAAS), the effect of coumarins started before the procedure on early and late outcome was studied. Patients were randomised to aspirin only or to aspirin plus coumarins. Half of the patients were randomised to undergo six-month angiographic follow-up. Study medication was started one week before coronary angioplasty and the target international normalised ratio (INR) was 2.1-4.8 during angioplasty and six-month follow-up. 'Optimal' anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. In addition, cost-effectiveness of coumarin treatment was measured. At one year death, myocardial infarction, target-lesion revascularisation and stroke were observed in 14.3% of the 530 patients randomised to aspirin plus coumarin versus in 20.3% of the 528 patients randomised to aspirin alone (relative risk 0.71; 95% CI 0.54-0.93). The incidence of major bleedings and false aneurysms during hospitalisation was 3.2% and 1.0%, respectively, (relative risk 3.39; 95% CI 1.26-9.11). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19-0.57). Quantitative coronary analysis was performed of 301 lesions in the ASA group and of 297 lesions in the coumarin group. At six months, the minimal luminal diameter was similar in the ASA and coumarin group. However, optimal anticoagulation was an independent predictor of angiographic outcome at six months. Optimal anticoagulation led to a 0.21 mm (95% CI: 0.05-0.37) larger MLD as compared with suboptimal anticoagulation whereas aspirin use led to a 0.12 mm (95% CI -0.28-0.04) smaller MLD. When including all costs, the savings associated with coumarin
Córdoba, Juan Pablo; Larrarte, Carolina; Ruiz, Alvaro
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.
Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.
Sambola, Antonia; Montoro, J Bruno; Del Blanco, Bruno García; Llavero, Nadia; Barrabés, José A; Alfonso, Fernando; Bueno, Héctor; Cequier, Angel; Serra, Antonio; Zueco, Javier; Sabaté, Manel; Rodríguez-Leor, Oriol; García-Dorado, David
Oral anticoagulation (OAC) is the recommended therapy for patients with atrial fibrillation (AF) because it reduces the risk of stroke and other thromboembolic events. Dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention and stenting (PCI-S). In patients with AF requiring PCI-S, the association of DAPT and OAC carries an increased risk of bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of developing new ischemic or thromboembolic events. The MUSICA-2 study will test the hypothesis that DAPT compared with triple therapy (TT) in patients with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score ≤2) after PCI-S reduces the risk of bleeding and is not inferior to TT for preventing thromboembolic complications. The MUSICA-2 is a multicenter, open-label randomized trial that will compare TT with DAPT in patients with AF and CHADS2 score ≤2 undergoing PCI-S. The primary end point is the incidence of stroke or any systemic embolism or major adverse cardiac events: death, myocardial infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI-S. The secondary end point is the combination of any cardiovascular event with major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304 patients. The MUSICA-2 will attempt to determine the most effective and safe treatment in patients with nonvalvular AF and CHADS2 score ≤2 after PCI-S. Restricting TT for AF patients at high risk for stroke may reduce the incidence of bleeding without increasing the risk of thromboembolic complications. © 2013.
Vicente, Vicente; Martín, Alfonso; Lecumberri, Ramón; Coll-Vinent, Blanca; Suero, Coral; González-Porras, José Ramón; Marco, Pascual; Mateo, José; Roldán, Vanesa; Soulard, Stéphane; Crespo, Carlos; Camats, Míriam
To evaluate the level of agreement between hematologists and emergency medicine physicians regarding the best clinical practices for managing bleeding and anticoagulant reversal. Nationwide Spanish multicenter Delphi method study with a panel of experts on anticoagulation and the management of bleeding. Two survey rounds were carried out between April and September 2015. Consensus was reached when more than 75% of the panelists scored items in the same tertile. Fifteen hematologists and 17 emergency medicine specialists from 14 Spanish autonomous communities participated. Consensus was reached on the use of both hemodialysis and an activated prothrombin complex concentrate (PCC) to antagonize significant/major bleeding in patients taking dabigatran. Use of an activated PCC was considered sufficient for patients on rivaroxaban or apixaban. The panel did not consider any PCC to be both effective and safe. Tests for activated partial thromboplastin, thrombin, diluted thrombin, and ecarin clotting times were considered useful in patients treated with dabigatran. A specific anti-Xa activity assay was suggested for patients who developed bleeds while treated with rivaroxaban or apixaban. Specific antidotes for direct-acting oral anticoagulants would be useful when severe bleeding occurs according to 97% of the panelists. Such antidotes would substantially change current treatment algorithms. The points of consensus were generally in line with clinical practice guidelines, but the Delphi process revealed that there are aspects of the clinical management of bleeding that require unified criteria. The need for specific antidotes for direct-acting oral anticoagulants was emphasized.
Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria
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
Komatsu, Takashi; Tachibana, Hideaki; Satoh, Yoshihiro; Ozawa, Mahito; Kunugita, Fusanori; Ueda, Hironobu; Nakamura, Motoyuki
The CHA(2)DS(2)-VASc score has been newly proposed for stratifying patients with nonvalvular atrial fibrillation (AF) according to the risk of ischemic stroke in the 2010 European Society of Cardiology guideline. However, there is little information about its usefulness for predicting long-term prognosis of cardiovascular events in Japanese patients with paroxysmal AF. This study retrospectively included 332 paroxysmal AF patients (224 men, mean age 65±13 years, mean follow-up period 53±35 months) without receiving anticoagulant therapy between June 1995 and August 2008 who were categorized into risk stratification on the basis of CHA(2)DS(2)-VASc score. The distribution of CHA(2)DS(2)-VASc scores was 0, 1, 2, 3, 4, 5, 6, and 7 points in 76 (23%), 60 (18%), 69 (21%), 69 (21%), 28 (8%), 23 (7%), 6 (2%), and 1 (0.3%) patients, respectively. The annual rates of symptomatic ischemic stroke were 0%, 0.60%, 0.95%, 1.96%, 5.45%, 9.06%, and 13.7% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5, and ≥6 points, respectively (p<0.001) and those of cardiovascular events including hospitalization for thromboembolism, heart failure and cardiovascular death were 0%, 1.43%, 1.50%, 2.52%, 10.14%, 12.85%, and 17.13% when the CHA(2)DS(2)-VASc score was 0, 1, 2, 3, 4, 5 and ≥6 points, respectively (p<0.001). Higher CHA(2)DS(2)-VASc scores were associated with greater annual rates of ischemic stroke and cardiovascular events. In a multivariate logistic regression analysis adjusted for the potentially confounding variables, the CHA(2)DS(2)-VASc score was associated with symptomatic ischemic stroke (odds ratio 7.051, 95% confidence interval 3.76-13.22, p<0.001) and cardiovascular events (odds ratio 3.448, 95% confidence interval 2.33-5.11, p<0.001). In Japanese patients with paroxysmal AF, the CHA(2)DS(2)-VASc score is a useful scheme for risk stratification of ischemic stroke and cardiovascular events. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier
Gemmati, Donato; Burini, Francesco; Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria; Tisato, Veronica; Gaudio, Rosa Maria
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. 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. 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 that the combination of VKORC1 and CYP2C
Graham, S P
The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class
Hoffman, Janet L; Aneese, Nadia J; Schmidt, Kyle J; Chaben, Alex C; Smythe, Maureen A
The University HealthSystem Consortium (UHC), a national hospital engagement network (HEN), establishes health-system metrics to assess and improve quality of care. In 2012, a metric for inpatient anticoagulant hemorrhage was developed. The utility of this metric to improve anticoagulation care has not been assessed. To identify opportunities to improve anticoagulation safety through the use of a HEN metric for inpatient anticoagulant-associated hemorrhage. This was a single-center, retrospective, observational study of metric identified patients with presumed inpatient anticoagulant hemorrhage. Records were reviewed to confirm anticoagulant hemorrhage and identify bleed site and severity. A structured process was used to assess bleed preventability and subsequently identify opportunities for improving care. Each bleed was reviewed by 2 investigators. Anticoagulant hemorrhage was confirmed in 85.9% (61/71) with heparin infusion the most common anticoagulant. Patients were primarily medical, with a mean age of 72.7 ± 15 years. The most common bleed sites were gastrointestinal (24.6%) and retroperitoneal (21.3%). Major bleeding occurred in 60.7% (37/61). Anticoagulant hemorrhage was preventable in 18% (11/61) of cases with heparin protocol noncompliance the most common cause of a preventable bleed. Several opportunities for improving heparin infusion therapy were recognized and protocol changes were implemented. The UHC metric accurately captures inpatient anticoagulant-associated hemorrhage the majority of time. The UHC metric on anticoagulant-associated hemorrhage can be a useful part of a health system's overall plan for the safe use of anticoagulants in the hospital setting. © The Author(s) 2015.
Gómez-Outes, Antonio; Suárez-Gea, Ma Luisa; Calvo-Rojas, Gonzalo; Lecumberri, Ramón; Rocha, Eduardo; Pozo-Hernández, Carmen; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio
The history of the traditional anticoagulants is marked by both perseverance and serendipity. The anticoagulant effect of heparin was discovered by McLean in 1915, while he was searching for a procoagulant in dog liver. Link identified dicumarol from spoiled sweet clover hay in 1939 as the causal agent of the sweet clover disease, a hemorrhagic disorder in cattle. Hirudin extracts from the medicinal leech were first used for parenteral anticoagulation in the clinic in 1909, but their use was limited due to adverse effects and difficulties in achieving highly purified extracts. Heparins and coumarins (i.e.: warfarin, phenprocoumon, acenocoumarol) have been the mainstay of anticoagulant therapy for more than 60 years. Over the past decades, the drug discovery paradigm has shifted toward rational design following a target-based approach, in which specific proteins, or "targets", are chosen on current understandings of pathophysiology, small molecules that inhibit the target's activity may be identified by high-throughput screening and, in selected cases, these new molecules can be developed further as drugs. Despite the application of rational design, serendipity has still played a significant role in some of the new discoveries. This review will focus on the discovery of the main anticoagulant drugs in current clinical use, like unfractionated heparin, low-molecular-weight heparins, fondaparinux, coumarins (i.e.: warfarin, acenocoumarol, phenprocoumon), parenteral direct thrombin inhibitors (DTIs) (i.e.: argatroban, recombinant hirudins, bivalirudin), oral DTIs (i.e.: dabigatran) and oral direct factor Xa inhibitors (i.e.: rivaroxaban, apixaban).
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
Wheeler, D S; Giugliano, R P; Rangaswami, J
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.
Dilute Russell's viper venom (DRVV) testing and activated partial thromboplastin time (APTT) have been effectively used in combination for lupus anticoagulant testing. The purpose of our study was to evaluate the role of mixing in activated partial thromboplastin and dilute Russell's viper venom testing for evaluation of lupus anticoagulants. Citrated blood from patients who were not on oral anticoagulant therapy was studied. Mixing study with 1 : 1 normal plasma for elevated APTT and also few samples with elevated screen time was carried out. Elevated APTT was seen in only 48.1% of patients with lupus anticoagulant. Correction of APTT was seen in 27.8% of lupus anticoagulant-positive patients. DRVV test on mixing resulted in 83.8% false-negative values. Integrated DRVV test could be a standalone test for testing lupus anticoagulant. Mixing study may be restricted for patients on oral anticoagulants or patients with strong lupus anticoagulant.
Kim, Se-Kwon; Wijesekara, Isuru
Recently, a great deal of interest has been developed in the nutraceutical and pharmaceutical industries to isolate natural anticoagulant compounds from marine resources. Among marine resources, marine algae are valuable sources of novel bioactive compounds with anticoagulant effect. Phlorotannins and sulfated polysaccharides such as fucoidans in brown algae, carrageenans in red algae, and ulvans in green algae have been recognized as potential anticoagulant agents. Therefore, marine algae-derived phlorotannins and SPs have great potential for developing as anticoagulant drugs in nutraceutical and pharmaceutical areas. This chapter focuses on the potential anticoagulant agents in marine algae and presents an overview of their anticoagulant effect. Copyright © 2011 Elsevier Inc. All rights reserved.
Dyla, Agnieszka; Mielnicki, Wojciech; Bartczak, Joanna; Zawada, Tomasz; Garba, Piotr
Liver failure is a serious and often deadly disease often requiring MARS (Molecular Adsorbent Recirculating System) therapy. Choosing the safe and effective method of anticoagulation during artificial liver support systems seems to be very difficult and extremely important. The aim of this study was to assess effectiveness and safety of regional anticoagulation with citrate in liver failure patients during MARS. We used a single center observational study. We analyzed 158 MARS sessions performed in 65 patients: 105 (66.5%) sessions in 41 patients with heparin anticoagulation, 40 (25.3%) sessions in 19 patients with citrate, and 13 (8%) sessions in only five patients without anticoagulation, that were excluded from part of the analysis. To determine the effectiveness of regional anticoagulation with citrate, probability of filter survival and changes in laboratory parameters were analyzed according to the applied method of anticoagulation. The safety of citrate was determined by Ca/Ca(2+) ratio, acid-base balance, bleeding complications, and the need for blood product transfusions. The probability of filter survival in the citrate group was 94% and in the heparin group 82% (P = 0.204). There was no relationship between the method of anticoagulation and effectiveness of MARS therapy in lowering the levels of the analyzed parameters. Only one patient had a Ca/Ca(2+) ratio higher than he safety margin. There were no statistically significant changes in pH and lactate level irrespective of anticoagulation; bicarbonate dropped significantly only in the heparin group (P = 0.03). The frequency of bleeding complications and the need for transfusions did not differ significantly between groups. Regional anticoagulation with citrate can be an effective and safe method of anticoagulation during MARS therapy, but requires attentive monitoring and further studies in liver failure patients.
Daniels, Paul R
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.
Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio
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
Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study.
Fiedler, K Anette; Byrne, Robert A; Schulz, Stefanie; Sibbing, Dirk; Mehilli, Julinda; Ibrahim, Tareq; Maeng, Michael; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Sarafoff, Nikolaus
An increasing number of patients undergoing coronary stenting need lifelong anticoagulation and therefore require a triple therapy typically consisting of aspirin, clopidogrel, and a vitamin K antagonist. Triple therapy confers an elevated bleeding risk as compared with dual therapy; however, omission of either antiplatelet or anticoagulation therapy might increase the risk of stent thrombosis or thrombembolic events. Although guidelines recommend a duration of dual antiplatelet therapy of 6 to 12months after drug-eluting stent (DES) implantation, the optimal duration of dual antiplatelet therapy in patients receiving oral anticoagulation is not known. We postulate that 6-week clopidogrel therapy after DES implantation as compared with 6-month therapy is associated with improved clinical outcomes in patients undergoing DES implantation receiving concomitant aspirin and vitamin K antagonists. The ISAR-TRIPLE is a randomized, open-label trial that examines the restriction of clopidogrel therapy from 6 months to 6 weeks after DES implantation in the setting of concomitant aspirin and oral anticoagulant. Patients are randomized in a 1:1 fashion to either 6-week or 6-month clopidogrel therapy. The primary end point is a composite of death, myocardial infarction, definite stent thrombosis, stroke, or major bleeding. The secondary end point comprises ischemic and bleeding complications. According to sample size calculations, a total of 600 patients are required to be enrolled. Clinical follow-up is scheduled at 6 weeks and at 6 and 9 months after randomization. There is clinical equipoise regarding the optimal duration of triple therapy after DES implantation in patients who need vitamin K antagonist therapy. The ISAR-TRIPLE trial aims to test the hypothesis that a 6-week triple therapy compared with a 6-month triple therapy improves net clinical outcomes. Copyright © 2014 Mosby, Inc. All rights reserved.
Albaladejo, Alberto; Alvarado, Alfonso
Background A new group of oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. Patients being treated with oral anticoagulants are at higher risk for bleeding when undergoing dental treatments. Material and Methods A literature search was conducted through April 2016 for publications in the ISI Web of Knowledge, PubMed and Cochrane Library using the keywords “dabigatran”, “rivaroxaban”, “apixaban”, “edoxaban”, “new oral anticoagulants”, “novel oral anticoagulants”, “bleeding” and “dental treatment”. Results There is no need for regular coagulation monitoring of patients on dabigatran therapy. Whether or not to temporarily discontinue dabigatran must be assessed according to the bleeding risk involved in the dental procedure to be performed. Conclusions The number of patients under treatment with new oral anticoagulants will increase in the coming years. It is essential to know about the pharmacokinetics and pharmacodynamics of new oral anticoagulants and about their interactions with other drugs. It is necessary to develop clinical guidelines for the perioperative and postoperative management of these new oral anticoagulants in oral surgical procedures, and to carefully evaluate the bleeding risk of dental treatment, as well as the thrombotic risk of suppressing the new oral anticoagulant. Key words:Dabigatran, rivaroxaban, apixaban, edoxaban, novel oral anticoagulants, bleeding. PMID:28210451
Sidoti, Anna; Brogi, Etrusca; Morse, Joshua; Collareta, Michele; Vetrugno, Luigi; Giunta, Francesco; Forfori, Francesco
Direct hemoperfusion with polymyxin B (PMX-DHP) is an extracorporeal treatment to add to conventional therapy during unresponsive endotoxic septic shock. So far, only heparin has been used as an anticoagulant during polymyxin B therapy. We present a case report of a postsurgical septic patient treated with 2 cycles of PMX-DHP using citrate anticoagulation. Monitoring of serum calcium, postcartridge calcium, and acid-base balance was performed. The treatments were accomplished without complications. To our knowledge, this is the first published report on the use of citrate anticoagulation during PMX-DHP. We conclude that citrate anticoagulation is feasible during hemoperfusion therapy in patients with increased hemorrhagic risk.
Tripodi, A; Chantarangkul, V; Clerici, M; Negri, B; Mannucci, P M
A key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrated whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.
Rojas-Hernandez, Cristhiam M; Garcia, David A
After the introduction of warfarin, long-term oral anticoagulation treatment remained unchanged for more than 50 years. Most recently, with the development and approval of new oral anticoagulants, the treatment of medical conditions that require thrombosis prophylaxis and long-term anticoagulation has become more complex. In the case of venous thromboembolism (VTE) prevention after orthopedic surgery, the new oral agents will be less costly than the parenteral alternative. In other settings (such as atrial fibrillation or treatment of acute VTE), the new agents will offer additional convenience at higher cost, but the degree to which they will reduce clinically important events such as thrombosis or bleeding will be limited, especially for patients on optimally controlled warfarin. As the use of the new oral anticoagulants becomes more widespread, it will be important for all clinicians to have a basic understanding of their pharmacology, advantages, and limitations. Although the need to measure or reverse the effect of these drugs will arise infrequently, clinicians--especially hematologists--will desire evidence-based recommendations about how to manage such scenarios, which will require research studies.
Eusébio, Jorge; Reny, Jean-Luc; Fontana, Pierr; Nendaz, Mathieu
If the benefits of antiplatelet and anticoagulant therapies are well established, bleeding complications appear underestimated in trials in comparison to their real-life incidence. Also, a large number of patients receive various associations of antiplatelet or anticoagulant treatments, while the benefit of some associations is not firmly established and data about their safety are missing. Identifying patients at high risk of bleeding is essential to define appropriate strategies. In this article we discuss the risk-benefit of various antiplatelet and anticoagulant molecules taken individually or in combination. An overview of the main clinical scores available to stratify the risk of bleeding is presented.
Pinède, Laurent; Ninet, Jacques
The curative anticoagulant treatment of venous thromboembolism is non fractionated heparin or low molecular weight heparin, secondly substituted by oral anticoagulant therapy. Early mobilisation and elastic contention should be systematically prescribed. Low molecular weight heparin once or twice a day and early substitution by vitamin K antagonist allow an ambulatory treatment for deep vein thrombosis. It is still recommended a hospital management for patients with symptomatic pulmonary embolism. It is necessary to tailor the duration of anticoagulation individually according to the extension of venous thromboembolism and the presence (or absence) of risk or triggering factors. Bleeding is the major risk of anticoagulant therapy, particularly the vitamin K antagonists, justifying patient's education, adapted and regular biological surveillance, co-ordinated care approach with practical recommendations, patient's self-monitoring.
González-Fajardo, José A; Martin-Pedrosa, Miguel; Castrodeza, Javier; Tamames, Sonia; Vaquero-Puerta, Carlos
We evaluated the effect of long-term anticoagulant treatment (enoxaparin vs coumarin) in patients with deep venous thrombosis (DVT) as to incidence of post-thrombotic syndrome (PTS) and recurrent venous thromboembolism. We also analyzed the impact of thrombus regression after the anticoagulant treatment for these two outcomes. A prospective study was designed in which 165 patients with symptomatic, unilateral, first-episode DVT were randomized to a long-term anticoagulant treatment with coumarin or enoxaparin during at least 3 months. The rate of thrombus regression was defined as the difference in Marder score after 3 months of treatment by venography. Follow-up was performed at 3, 6, and 12 months, and yearly thereafter for 5 years. Venous disease was related to pathologic severity of PTS according to the validated scale of Villalta as rated by a physician blinded to treatment. Recurrence of symptomatic venous thromboembolism was documented objectively. The 5-year follow-up period was completed for 100 patients (enoxaparin, 56; coumarin, 44). A lesser incidence of PTS was observed in the enoxaparin group (39.3% absent, 19.6% severe) than in the coumarin group (29.5% absent, 29.5% severe), although this difference was not statistically significant. The accumulated recurrence rate was 19.3% with enoxaparin compared with 36.6% with coumarin (P = .02). Although the mean Marder score was significantly improved in both groups (49.1% for enoxaparin vs 24.0% for coumarin; P = .016), a lower reduction in thrombus size was associated with higher clinical events of recurrence (hazard ratio = 1.97; 95% CI, 1.06-3.66; P = .032). A significant inverse correlation was also found between the degree of thrombus regression at 3 months and the incidence at 5 years of PTS (P = .007). Residual venous thrombosis is an important risk factor for recurrent thromboembolism and PTS. A greater reduction in thrombus size was associated with lesser clinical events of recurrence and
Garcia, David A; Baglin, Trevor P; Weitz, Jeffrey I; Samama, Meyer Michel
This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
Altenburg, Alexander; Haage, Patrick
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.
Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T
To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant
Cerebral venous sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy: how long should we treat these patients with warfarin?
Jukic, Ivana; Titlic, Marina; Tonkic, Ante; Rosenzweig, Daniel
Cerebral venous sinus thrombosis is an uncommon condition with many clinical manifestations, and hereditary prothrombotic conditions such as factor Leiden V, deficiency of protein S, protein C and antithrombin III, as well as prothrombin gene mutation, may account for 10-15% of cases. To date, conflicting results have been reported for recurrent venous thrombosis in the patients with factor V Leiden and prothrombin G20210A mutation, since some studies have shown a higher risk for recurrent venous thrombosis in carriers of these two mutations than in non-carriers, and the last study showed higher risk only for carriers of double defect (homozygous or double heterozygous for this mutations). Case report is presented. We report a case of cerebral sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy. Since many facts are controversial, the use of secondary prophylaxis for thrombosis in these patients is still a matter of debate without clear consensus recommendation. Data on the risk of recurrent thrombotic events in thrombophilic patient is insufficient. The main unclear question concerning these patients is: how long and whom should we treat with long-term anticoagulant therapy as secondary prophylaxis of DVT? The problem for practitioner is that we do not have guidelines and precise recommendations for secondary thromboprophylaxis in this or similar cases. This case is remarkable for its favorable and quick outcome and its rarity, because CSVT is an uncommon condition and heterozygous prothrombin G20210A genotype was only found predisposing factor for CSVT. Further studies of risk of recurrent venous thrombosis in patients with heterozygous prothrombin G20210A genotype with the larger sample size are required.
Brejcha, M; Gumulec, J; Penka, M; Klodová, D; Wróbel, M; Bogoczová, E
The management of warfarin therapy in patients undergoing surgery or other invasive procedures involves a balance between the risk of hemorrhage, and the risk of thrombosis. Risk of hemorrhage and the trombosis depends on the type of procedure and on pre-existing conditions. Procedures with low risk of hemorrhage (dental, dermatologic or ophtalmologic procedures, endoscopy) can be provided with continuing anticoagulant therapy. Surgery with high hemorrhagic risk need stop warfarin and start bridging anticoagulant therapy, such as unfractionated heparin or low molecular weight heparin, prior and after surgery. In patients requiring emergency surgery, vitamin K, prothrombin complex concentrate or fresh frozen plasma can be used to improve coagulation.
Barnes, Geoffrey D.; Nallamothu, Brahmajee K.; Sales, Anne E.; Froehlich, James B.
Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban), many have questioned the need for anticoagulation clinic. However, we believe the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline three key purposes that a “re-imagined” anticoagulation clinic would serve: 1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), 2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and 3) to encourage ongoing adherence to these life-saving medications. We also describe how re-purposing anticoagulation clinics as broader “medication safety clinics” would promoting safe and effective care across a range of cardiovascular conditions for high-risk medications (e.g. spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a re-imagined anticoagulation or medication safety clinic structure. PMID:26933047
Barnes, Geoffrey D; Nallamothu, Brahmajee K; Sales, Anne E; Froehlich, James B
Anticoagulation clinics were initially developed to provide safe and effective care for warfarin-treated patients with atrial fibrillation, venous thromboembolism, and mechanical valve replacement. Traditionally, these patients required ongoing laboratory monitoring and warfarin dose adjustment by expert providers. With the introduction of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), many have questioned the need for anticoagulation clinic. However, we think that the growing number of oral anticoagulant choices creates an urgent need for expanding the traditional role of the anticoagulation clinic. We outline 3 key purposes that a reimagined anticoagulation clinic would serve: (1) to assist patients and clinicians with selecting the most appropriate drug and dose from a growing list of anticoagulant options (including warfarin), (2) to help patients minimize the risk of serious bleeding complications with careful long-term monitoring and peri-procedural management, and (3) to encourage ongoing adherence to these life-saving medications. We also describe how repurposing anticoagulation clinics as broader medication safety clinics would promote safe and effective care across a range of cardiovascular conditions for high-risk medications (eg, spironolactone, amiodarone). Finally, we highlight a few existing health systems that are overcoming key challenges to implementing a reimagined anticoagulation or medication safety clinic structure.
This study evaluated 44 separate medication withdrawal periods in 17 subjects who were attending a hospital anticoagulation clinic for management of anticoagulation medication. The data suggest that when anticoagulant withdrawal is needed for particular dental procedures, a 2-day hold is an effective period of medication withdrawal. No thromboembolic events were observed after any of the withdrawal periods. Further, no posttreatment hemorrhagic episodes were observed when the anticoagulant medication was reinstituted after dental treatment. Prothrombin time blood levels should be determined in the immediate pretreatment period, however, because the prothrombin time can fluctuate even in the best maintained patients.
Dang, Yi-Ping; Chen, Yun-Fei; Li, Yi-Qing; Zhao, Lei
Deep Vein Thrombosis (DVT) has been known as a common medical problem all over the world. Thrombus traveling in blood vessels may lead to pulmonary embolism (PE), associated with high rates of mortality. Anticoagulant therapy is the mainstay treatment of DVT. Common anticoagulants, Vitamin K antagonists (VKAs), unfractionated heparin (UFH) and Low-molecular-weight heparin (LMWH) have been used in clinical application over decades, but can increase the risk of hemorrhage. Thereby, several new oral anticoagulants (NOACs) have been developed, which includes direct thrombin inhibitors (DTI) and direct factor Xa inhibitors. To be contrast with VKAs and UFH, NOACs have many advantages such as rapid offset action, few drug/food interactions and no need for routine coagulation monitoring, etc. Many NOACs are still being evaluated in Phase III clinical trials such as Betrixaban and Darexaban (YM150). However, NOACs still have problems to be solved such as lack of antidotes and laboratory monitoring, high drug costs, etc. Besides, several agents have already shown the potential to be new anticoagulants. Factor Xa play an important role in thrombin generation and coagulation pathway. Thus, the new compounds directly targeting on factor Xa for prevention DVT are highly anticipated. DPC423, a new series of 6-substituted coumarin derivatives and Phenyltriazolinones as potent factor Xa inhibitors have been recently reported. Recent studies revealed that agents extracted from botanicals not only have anti-coagulant effects but also possess other pharmacological activities such as anti-inflammation to alleviate the post-thrombotic syndromes. All the evidence above suggests that many new compounds might have great potential to be more effective and safe oral anticoagulants.
Vogel, T; Geny, B; Kaltenbach, G; Lang, P-O
Prescribing anticoagulant therapy when the CHA₂DS₂-VASc score is ≥ 1 prevents strokes secondary to non-valvular atrial fibrillation (AF). However, it is important to remember that whether the aged population has the highest risk of stroke in case of AF, under anticoagulant therapy this population is also at the highest risk of bleeding. Vitamin K antagonists were for decades the molecules of reference with benefits even after 75 years of age. The direct oral anticoagulants have overcome the biological constraints inherent to monitoring vitamin K antagonists and provide a more stable pharmacological action with a limited number of drug-drug interactions. However, the widespread use of these molecules in the older population remains controversial. In this review article, indications and modalities of administration of anticoagulant therapy in the elderly will be detailed and discussed on the basis of the most recent recommendations proposed in particular by the European Society of Cardiology. Particular attention will be paid to new oral anticoagulant therapies compared with vitamin K antagonists and antiplatelet agents.
Maynar, Javier; Martínez-Sagasti, Fernando; Herrera-Gutiérrez, Manuel; Martí, Francisco; Candel, Francisco Javier; Belda, Javier; Castaño, Sergio; Sanchez-Izquierdo, José Ángel
High levels of endotoxin have been reported as a risk factor for mortality in critical patients. Toraymyxin® is a column designed to remove circulating blood endotoxin by direct hemoperfusion widely used in Japan. To evaluate the effect of direct hemoperfusion with Toraymyxin® (DHP-PMX) as an adjuvant treatment in patients with severe sepsis due to intestinal perforation in terms of hemodynamic function and coagulation abnormalities. Prospective cohort study with a historical control group. Cohort 1: prospective cohort undergoing two sessions of DHP-PMX (n=14). Cohort 2: retrospective historical cohort (n=7). The anticoagulation regime was used according to the protocol of each centre and to the special conditions of each patient. Mean norepinephrine dose was significantly reduced (0.9 ± 0.5 μg/kg/min pre-first DHP-PMX vs 0.3 ± 0.4 μg/kg/min post-second DHP-PMX treatment, p<0.05). Central venous pressure (CVP) and stroke volume variation (SVV) remained without significant changes during the study, as well as cardiac index (CI) in patients with initial CI ≥ 2.5 L/min/m2. CI significantly increased in patients with initial CI<2.5 L/min/m2 (2.1 ± 0.4 pre-first DHP-PMX vs 3.4 ± 0.4 pre-second DHP-PMX session, p=0.01). Mean platelet count pre-first and post-second DHP-PMX decreased significantly (213.9 x 10(3) ± 138.5 x 10(3) platelets/mm3 vs 91.0 x 10(3) ± 53.5 x 10(3) platelets/mm3, p=0.03), without significant changes during each DHP-PMX treatment. Patients did not experience bleeding nor complications derived from DHP-PMX treatments. Survival rates at 28 and 56 days did not differ significantly between cohort 1 and 2 (21.4% vs 42.9%; 42.9% vs 57.1%; respectively). Performing two sessions of DHP-PMX treatment in a cohort of patients with abdominal sepsis is a feasible adjuvant therapeutic approach, safe in terms of coagulation abnormalities, can be done with different anticoagulation protocols, improves hemodynamic status and may impact on survival.
Carter, Cedric J.
The author briefly reviews the use of anticoagulants, describing the specific tests their use requires. These tests are usually performed in a specialized laboratory. The clinical implication of the laboratory's use of different prothrombin time systems is explained. Implications of the use of oral anticoagulants in family practice are discussed. PMID:21253057
Tieken, Chris; Versteeg, Henri H
Venous thromboembolism (VTE) and cancer are strongly associated, and present a major challenge in cancer patient treatment. Cancer patients have a higher risk of developing VTE, although the risk differs widely between tumour types. VTE prophylaxis is routinely given to cancer patients, in the form of vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). Several studies have reported that cancer patients receiving anticoagulants show prolonged survival and this effect was more pronounced in patients with a good prognosis, although the mechanism is poorly understood. Tissue Factor (TF) is the initiator of extrinsic coagulation, but its non-haemostatic signalling via protease-activated receptors (PARs) is a potent driver of tumour angiogenesis. Furthermore, coagulation activation is strongly implicated in tumour cell migration and metastasis. This review discusses the effects of anticoagulants on cancer progression in patients, tumour cell behaviour, angiogenesis, and metastasis in in vitro and in vivo models. Inhibition of TF signalling shows great promise in curbing angiogenesis and in vivo tumour growth, but whether this translates to patients is not yet known. Furthermore, non-haemostatic properties of coagulation factors in cancer progression are discussed, which provide exciting opportunities on limiting oncologic processes without affecting blood coagulation. © 2016 Elsevier Ltd. All rights reserved.
Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky
Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.
Steinberg, M J; Moores, J F
Dental professionals frequently treat patients who are receiving anticoagulation therapy. Proper treatment may require adjustment of the anticoagulant dose usually on the basis of the patient's current prothrombin time. This test has been shown to be less accurate than previously thought. The international normalized ratio is another method that attempts to standardize the degree of anticoagulation and to improve reproducibility of results. This system is slowly being implemented in laboratories in the United States. Practitioners who treat patients taking anticoagulants need to be aware of this system in order to make appropriate management decisions.
Weitz, Jeffrey I.; Fredenburgh, James C.
Compared with vitamin K antagonists, the direct oral anticoagulants (DOACs) are simpler to administer and are associated with less intracranial bleeding. Nonetheless, even with the DOACs, bleeding still occurs and many patients with atrial fibrillation fail to receive anticoagulant thromboprophylaxis because of the fear of bleeding. Therefore, there is an urgent need for safer anticoagulants. Recent investigations into the biochemistry of hemostasis and thrombosis have identified new targets for development of novel anticoagulants. Using data from complementary sources, including epidemiological studies and investigations in various animal models, the contact pathway has emerged as a potential mediator of thrombosis that plays a minor part in hemostasis. Consequently, factor (F) XII of the contact system and FXI in the intrinsic pathway have been identified as potentially safer targets of anticoagulation than thrombin or FXa. However, further studies are needed to identify which is the better target for the appropriate indication. This review highlights the evidence for focusing on FXI and FXII and examines the novel approaches directed at these new targets. These emerging strategies should address current unmet medical needs and provide new avenues by which to improve anticoagulant therapy by reducing the risk of bleeding. PMID:28286749
Radaelli, Franco; Dentali, Francesco; Repici, Alessandro; Amato, Arnaldo; Paggi, Silvia; Rondonotti, Emanuele; Dumonceau, Jean Marc
Acute gastrointestinal bleeding represents the most common adverse event associated with the use of oral anticoagulant therapy. Due to increasing prescription of anticoagulants worldwide, gastroenterologists are more and more called to deal with bleeding patients taking these medications. Their management is challenging because several issues have to be taken into account, such as the severity of bleeding, the intensity of anticoagulation, the patient's thrombotic risk and endoscopy findings. The recent introduction into the marketplace of new direct oral anticoagulants, for whom specific reversal agents are still lacking, further contributes to make the decision-making process even more demanding. Available evidence on this topic is limited and practice guidelines by gastroenterology societies only marginally address key issues for clinicians, including when and how to reverse coagulopathy, the optimal timing of endoscopy and when and how to resume anticoagulation thereafter. The present paper reviews the evidence in the literature and provides practical algorithms to support clinicians in the management of patients on anticoagulants who present with acute gastrointestinal bleeding.
Broman, Marcus; Klarin, Bengt; Sandin, Karin; Carlsson, Ola; Wieslander, Anders; Sternby, Jan; Godaly, Gabriela
Since 2012, citrate anticoagulation is the recommended anticoagulation strategy for continuous renal replacement therapy (CRRT). The main drawback using citrate as anticoagulant compared with heparin is the need for calcium replacement and the rigorous control of calcium levels. This study investigated the possibility to achieve anticoagulation while eliminating the need for calcium replacement. This was successfully achieved by including citrate and calcium in all CRRT solutions. Thereby the total calcium concentration was kept constant throughout the extracorporeal circuit, whereas the ionized calcium was kept at low levels enough to avoid clotting. Being a completely new concept, only five patients with acute renal failure were included in a short, prospective, intensely supervised nonrandomized pilot study. Systemic electrolyte levels and acid-base parameters were stable and remained within physiologic levels. Ionized calcium levels declined slightly initially but stabilized at 1.1 mmol/L. Plasma citrate concentrations stabilized at approximately 0.6 mmol/L. All postfilter ionized calcium levels were <0.5 mmol/L, that is, an anticoagulation effect was reached. All filter pressures were normal indicating no clotting problems, and no visible clotting was observed. No calcium replacement was needed. This pilot study suggests that it is possible to perform regional citrate anticoagulation without the need for separate calcium infusion during CRRT.
Edmunds, Ian; Avakian, Zorik
The management of anticoagulated patients requiring surgery presents a challenge to hand surgeons. The risk of bleeding related complications needs to be weighed up against the increased risk of thrombotic events if anticoagulants are altered or ceased. There is literature reporting the safety of hand, skin, eye and dental surgery on patients taking anticoagulants, and there is literature highlighting the risks associated with altering regular anticoagulant medication. However, it is common practice to cease or alter patients' anticoagulants peri-operatively for hand surgery. We report a prospective study of 107 patients taking anticoagulants who underwent 121 hand operations from December 2005 to August 2009. There was only one significant complication, that being a haematoma which occurred in a patient taking clopidogrel. We conclude that interruption to therapy with warfarin (provided the INR is not greater than 3.0), clopidogrel or clopidogrel with aspirin is unnecessary for patients undergoing hand surgery.
Alikhani Pour, Mahdi; Sardari, Soroush; Eslamifar, Ali; Azhar, Abid; Rezvani, Mohammad; Nazari, Milad
Medicinal plants, as a complementary medicine, have been used to treat various diseases since ancient times. These plants have numerous beneficial applications and are the source of certain conventional drugs. In diseases such as stroke and ischemia, which are caused by several factors, abnormal coagulation is an important causative factor. Accordingly, novel and effective therapies such as herbal remedies should be practiced to prevent such lethal diseases. Using the available databases such as Google Scholar and PubMed, the previously reported anticoagulant compounds and plants possessing anticoagulant activity were identified and collected in two separate lists. Next, the fast and cost-effective cheminformatics methods incorporated in PubChem were applied to detect some compounds similar to reported anticoagulants. Subsequently, 15 native medical plants of Iran containing the potential anticoagulants were selected. The selected plants were purchased and chopped, and the potential compounds were extracted by ethanol. Then three concentrations of extracts (1, 10, and 100 µg per ml) were made. Finally, anticoagulant effect of the selected plants was evaluated by in vitro prothrombin time and activated partial thromboplastin time coagulation tests. Among the 15 selected medicinal plants, three plants, including Terminalia bellirica (P=0.0019), Astragalus arbusculinus (P=0.0021), and Origanum vulgare (P=0.0014) showed a more promising anticoagulant effect in comparison to the control. The anticoagulant activity was identified for the first time in these three plants. Further in vivo study and mechanism of action assay are required to be performed on these three plants, which could be suitable candidates for use as natural anticoagulant medicines.
Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E.; Mann, Kenneth G.
The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may
Draper, Evan; Parkhurst, Brandon; Carley, Blake; Krueger, Kori; Larson, Tonja; Griesbach, Sara
The goal of anticoagulation management programs is to prevent thrombosis while minimizing the risks of hemorrhage. Direct acting oral anticoagulants (DOACs) selectively inhibit coagulation proteins to inhibit thrombosis. Previous studies suggest patient monitoring and education provided through anticoagulation services enhance adherence and decrease adverse outcomes in patients receiving DOAC therapy. The objectives of this study were to describe DOAC prescribing adherence to anticoagulation service protocols and to observe whether enrollment in an anticoagulation service resulted in greater prescribing adherence to DOAC protocols. A retrospective cohort study evaluated all initial prescriptions of apixaban, dabigatran, and rivaroxaban at Marshfield Clinic from 19 October 2010 to 21 August 2014. Three algorithms analyzed patient and prescription data extracted from the organization's electronic health record and classified prescriptions as per protocol or not per protocol. The algorithms classified not per protocol prescriptions as off-label indication, renal impairment [estimated glomerular filtration rate (eGFR) <30 ml/min], hepatic impairment (rivaroxaban and apixaban), advanced age >74 years (dabigatran), dose too low, or dose too high. The analysis assessed whether enrollment in the Marshfield Clinic Anticoagulation Service DOAC monitoring process was associated with increased adherence to protocols. In aggregate, 72% of apixaban prescriptions, 52% of dabigatran prescriptions, and 70% of rivaroxaban prescriptions were per protocol. Off-label indications and dosage too low were the most common not per protocol reasons for apixaban and rivaroxaban prescriptions. Age ≥75 years and off-label indication were the most common not per protocol reasons for dabigatran prescriptions. Enrollment in the anticoagulation service process was not associated with increased adherence to protocols. A significant proportion of DOAC prescriptions did not adhere to protocol
Veltkamp, R; Hacke, W
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.
Eickhoff, Jennifer S; Wangen, Tina M; Notch, Katie B; Ferguson, Tanya J; Nickel, Travis W; Schafer, Amy R; Bush, Diana L
A patient education workgroup was developed on a progressive care medical/vascular surgical unit. The workgroup identified patient education needs regarding discharge education for postsurgical patients and those discharging with oral anticoagulants (OAC). Staff surveys aided the workgroup in identifying a need for additional discharge education for patients and families. After various methods of patient education were explored, it was determined the workgroup could best meet the needs of the patient population through a class format providing group discussion and interaction. Logistical details and class formatting were configured to meet both the needs of the patients and the nursing staff. Current institutional patient education pamphlets were used to develop the content for the class. Physician review and input were obtained during the development of the content. A patient education specialist was also consulted to ensure proper literacy levels were used. To meet the Joint Commission National Patient Safety Goal regarding anticoagulant safety, the content focused on home management, which included the following: knowledge of INR goal range, dietary factors, when to call the provider and safety precautions. Other topics to promote self-efficacy in anticoagulation therapy were also included in the content. Postclass evaluations completed by patients and families provided useful feedback for continuous improvement and patient satisfaction. Preliminary survey results indicate high patient satisfaction with the class. Plans include a quality improvement project to evaluate the effectiveness of the patient education class on OAC. Copyright © 2010. Published by Mosby, Inc.
Simultaneous administration of the anticoagulants acenocoumarol, phenprocoumon or chlorindion and the antirheumatic substance alclofenac in long term trials has no observable influence on the prothrombin time of stabilized patients. When the anticoagulant (acenocoumarol or phenprocoumon) and the alclofenac therapy are begun simultaneously, a variation of the dose is necessary. Either a one-third lower initial dosage can be given, or, after attaining the maximal anticoagulation effect on the prothrombin time (48 h after beginning acenocoumarol therapy, 72 h with phenprocoumarol), a lower daily dosage must be administered once, in comparison to the other group without alclofenac therapy. The maintenace dosage is not influenced by alclofenac.
Objective: Oral anticoagulants are widely administered to patients with atrial fibrillation in order to prevent the onset of cardiogenic embolisms. However, intracranial bleeding during anticoagulant therapy often leads to fatal outcomes. Accordingly, the use of novel oral anticoagulants (NOACs), which less frequently have intracranial bleeding as a complication, is expanding. A nationwide survey of intracranial bleeding and its prognosis in Japan reported that intracranial bleeding of advanced severity was not common after NOAC administration. In this report, two cases from our institute are presented. Patients: Case 1 was an 85-year-old man with a right frontal lobe hemorrhage while under dabigatran therapy. Case 2 was an 81-year-old man who had cerebellar hemorrhage while under rivaroxaban therapy. Result: In both patients, the clinical course progressed without aggravation of bleeding or neurological abnormalities once anticoagulant therapy was discontinued. Conclusion: These observations suggest that intracranial hemorrhage during NOAC therapy is easily controlled by discontinuation of the drug. NOAC administration may therefore be appropriate despite the risk of such severe complications. Further case studies that include a subgroup analysis with respect to each NOAC or patient background will be required to establish appropriate guidelines for the prevention of cardiogenic embolisms in patients with atrial fibrillation. PMID:27928459
Wooten, James M
For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug.
Biasiutti, F Demarmels; Strebel, J Kremer Hovinga
For haemostatic and circulatory reasons pregnancy is associated with an about 6-fold relative increase of thrombotic risk which is further raised by additional risk factors, such as history of thrombosis or acquired and hereditary thrombophilia, respectively. Recently, the thrombophilias have been revealed as risk factors for severe preeclampsia, abruptio placentae, fetal growth retardation, abortion and still birth as well. Thus, there are several situations in which the question for the need of antithrombotic medication is raised in a pregnant woman, either for therapy of acute thromboembolism or for prophylaxis of thrombosis and obstetrical complications, respectively. While acute thromboembolism has to be treated in every case, indication for prophylaxis has to be weighed in the light of the individual risk profile of the pregnant woman and the potential side effects and inconvenience of the medication. The first part of this article deals with the pregnancy related problems of coumarins, heparins and aspirin and demonstrates that the low molecular weight heparins are the anticoagulants of choice for most indications in pregnancy. The second part of this overview shows in which specific situations and how the antithrombotic medications mentioned above are used in pregnancy.
Ciurus, Tomasz; Cichocka-Radwan, Anna
Introduction The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. Material and methods We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. Results The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). Conclusions The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID:26855650
Hijazi, Ziad; Oldgren, Jonas; Andersson, Ulrika; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Reilly, Paul A; Yusuf, Salim; Siegbahn, Agneta; Wallentin, Lars
To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial. GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment. GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores. In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment. Copyright © 2017 Elsevier Inc. All rights reserved.
Babilonia, Katrina; Trujillo, Toby
Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting.
Over the past several years a new era for patients requiring anticoagulation has arrived. The approval of new target specific oral anticoagulants offers practitioners several advantages over traditionally used vitamin K antagonist agents including predictable pharmacokinetics, rapid onset of action, comparable efficacy and safety, all without the need for routine monitoring. Despite these benefits, hemorrhagic complicates are inevitable with any anticoagulation treatment. One of the major disadvantages of the new oral anticoagulants is lack of specific antidotes or reversal agents for patients with serious bleeding or need for urgent surgery. As use of the new target specific oral anticoagulants continues to increase, practitioners will need to understand both the pharmacodynamics and pharmacokinetic properties of the agents, as well as, the available literature with use of non-specific therapies to reverse anticoagulation. Four factor prothrombin complex concentrates have been available for several years in Europe, and recently became available in the United States with approval of Kcentra. These products have shown efficacy in reversing anticoagulation from vitamin K antagonists, however their usefulness with the new target specific oral anticoagulants is poorly understood. This article will review the properties of dabigatran, rivaroxaban and apixaban, as well as the limited literature available on the effectiveness of prothrombin complex concentrates in reversal of their anticoagulant effects. Additional studies are needed to more accurately define the role of prothrombin complex concentrates in patients with life threatening bleeding or who require emergent surgery, as current data is both limited and conflicting. PMID:24742134
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
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.
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
Dannemiller, Robert; Ward, Tucker; Fanikos, John
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.
Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel
Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis.
Mommsen, Jens; Rodríguez-Fernández, Javier; Mateos-Micas, Mario; Vázquez-Bouso, Olga; Gumbao-Grau, Victor; Forteza-Gonzalez, Gabriel
Amputation of the auricle is a periodic occurrence leading to disfigurement if not treated properly. Venous stasis is a common complication in reattachments and requires decongestant and anticoagulant treatment. Today, leech therapy is the treatment of choice. Common problems are that it is not available everywhere and that it is usually contraindicated in anticoagulated patients. The peculiarities of leech therapy and the various aspects of surgical management are reviewed. A case of a partial amputation of the auricle in a patient under concomitant anticoagulation therapy with warfarin is presented. The amputated part was reattached in another hospital without microvascular anastomosis. The patient presented to our department with early signs of venous congestion. Leech therapy was started 35 hours after trauma, and the patient continued his anticoagulation therapy. With this treatment, 90% of the amputated part was rescued. The anticoagulation therapy of the patient may have played an important role in the first hours after reattachment, preventing capillary thrombosis and in consequence facilitating the minimal oxygenation necessary. The claim that anticoagulation therapy is a contraindication to leeching should be questioned in cases of reattachments in well-controllable locations without arterial anastomosis. PMID:22655116
Mas, Jean-Louis; Derumeaux, Geneviève; Guillon, Benoît; Massardier, Evelyne; Hosseini, Hassan; Mechtouff, Laura; Arquizan, Caroline; Béjot, Yannick; Vuillier, Fabrice; Detante, Olivier; Guidoux, Céline; Canaple, Sandrine; Vaduva, Claudia; Dequatre-Ponchelle, Nelly; Sibon, Igor; Garnier, Pierre; Ferrier, Anna; Timsit, Serge; Robinet-Borgomano, Emmanuelle; Sablot, Denis; Lacour, Jean-Christophe; Zuber, Mathieu; Favrole, Pascal; Pinel, Jean-François; Apoil, Marion; Reiner, Peggy; Lefebvre, Catherine; Guérin, Patrice; Piot, Christophe; Rossi, Roland; Dubois-Randé, Jean-Luc; Eicher, Jean-Christophe; Meneveau, Nicolas; Lusson, Jean-René; Bertrand, Bernard; Schleich, Jean-Marc; Godart, François; Thambo, Jean-Benoit; Leborgne, Laurent; Michel, Patrik; Pierard, Luc; Turc, Guillaume; Barthelet, Martine; Charles-Nelson, Anaïs; Weimar, Christian; Moulin, Thierry; Juliard, Jean-Michel; Chatellier, Gilles
Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization
Mani, Helen; Hellis, Mirna; Lindhoff-Last, Edelgard
Sodium citrate is the most commonly used anticoagulant for platelet function testing. However, the use of citrated blood for platelet function analysis has been criticized due to creation of a non-physiological milieu. Moreover, platelet function measurements performed with citrated blood need to be completed within 4 h after blood collection. Alternatively, hirudin and recently, a dual thrombin/factor Xa inhibitor benzylsulfonyl-D-Arg-Pro-4-amidinobenzylamide (BAPA), can be used to improve the reactivity after prolonged storage of platelets. The present study investigated platelet function tests using hirudin and BAPA anticoagulated blood. Blood was obtained from 30 healthy individuals and 20 patients on aspirin or clopidogrel therapy, and stored for 2, 12, 24 or 48 h. Light transmission aggregometry and impedance platelet aggregometry were performed using adenosine 5-diphosphate (ADP) and arachidonic acid as agonists. The vasodilator stimulated phosphoprotein (VASP) phosphorylation assay was evaluated. Platelet aggregation measurements of healthy individuals and patients showed stable platelet aggregation values induced by arachidonic acid, after 24 h, when hirudin or BAPA anticoagulated blood was used. However, citrated blood resulted in significantly reduced platelet response after 12 h. ADP-induced light transmission aggregation of healthy individuals and patients exhibited unchanged platelet aggregation after 12 h using hirudin or BAPA anticoagulated blood, while significantly reduced platelet response was observed after 12 h when using citrated blood. In contrast, measurement of ADP-induced aggregation by use of impedance aggregometry resulted in reduced stability over 12 h using hirudin or BAPA anticoagulated blood. The VASP assay exhibited no significant changes in results over a storage period of 48 h, independent of the anticoagulants used. Use of hirudin or BAPA anticoagulated blood resulted in improvement of stability of platelet function measurements.
Witt, Daniel M; Humphries, Tammy L
Analysis of the outcomes associated with episodes of excessive anticoagulation (international normalized ratio [INR] > 6.0) managed by physicians in a group model health maintenance organization (HMO) revealed opportunities for improvement. A centralized, telephone follow-up Clinical Pharmacy Anticoagulation Service (CPAS) was later implemented in the same HMO. We sought to compare the outcomes of excessive anticoagulation episodes managed by CPAS pharmacists to traditional physician management. Computerized laboratory information was used to identify episodes of excessive anticoagulation managed by CPAS clinical pharmacists during the 6-month study. Pertinent data were collected through retrospective medical record review. Results were compared to a similar analysis conducted prior to CPAS implementation (traditional management). A total of 313 INR episodes >6.0 were identified in the CPAS group compared to 301 in the traditional management group. 6.3% of patients in the traditional management group experienced major bleeding compared to 1.3% in the CPAS group (p = 0.001). The majority of excessive anticoagulation episodes in both groups were managed by temporarily withholding warfarin therapy. Phytonadione was administered more frequently in the traditional management group than the CPAS group, 17.0% vs. 6.4%, respectively (p < 0.001). Traditional management patients also received higher doses of phytonadione than CPAS patients, 13.0 mg vs. 3.3 mg, respectively (p < 0.001). Aggressive use of phytonadione in the traditional management group resulted in two episodes of iatrogenic thromboembolism while no such episodes occurred in the CPAS group. The management of excessive anticoagulation by a centralized telephone follow-up anticoagulation service staffed by clinical pharmacists resulted in improved clinical outcomes compared to traditional management.
O'Connell, John Edward; Stassen, Leo F A
Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. Over the last 40 years, warfarin has been the oral anticoagulant of choice and has been considered the mainstay of treatment. However, its use is limited by a narrow therapeutic index and complex pharmacodynamics, necessitating regular monitoring and dose adjustments. Recently, two new oral anticoagulants--dabigatran etexilate (a direct thrombin inhibitor) and rivaroxiban (a factor Xa inhibitor)--have been approved for use in North America and Europe. Unlike warfarin, dabigatran and rivaroxiban are relatively small molecules that work as anticoagulants by targeting specific single steps of the coagulation cascade. Their advantages, relative to warfarin, include: predictable pharmacokinetics; limited food and drug interactions; rapid onset of action; and, short half-life. They require no monitoring. However, they lack a specific reversal agent. The number of patients taking dabigatran and rivaroxaban is increasing. Therefore, it is inevitable that dentists will be required to perform invasive procedures on this cohort of patients. This paper outlines the various properties of the new oral anticoagulants and the most recent guidelines regarding the management of these dental patients taking these medications.
Costopoulos, Charis; Niespialowska-Steuden, Maria; Kukreja, Neville; Gorog, Diana A
Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide with a prevalence that has now reached pandemic levels as a consequence of the rapid modernization of the developing world. Its presentation as an acute coronary syndrome (ACS) is a frequent reason for hospital admission and of profound implications for personal, societal and global health. Despite improvements in the management of ACS with anti-platelet and anticoagulant therapy and revascularization techniques, many patients continue to suffer recurrent ischemic events. The need to reduce future cardiovascular events has led to the development of novel therapies to prevent coronary thrombosis, targeting thrombin-mediated pathways. These include direct Xa inhibitors (apixaban, rivaroxaban and darexaban), direct thrombin inhibitors (dabigatran) and PAR 1 antagonists (vorapaxar and atopaxar). This article critically reviews the comparative mechanisms of action, the risks and benefits, together with the clinical evidence base for the use of these novel oral agents in the management of ACS patients.
Willbanks, O L; Willbanks, S E
Femoral neuropathy occurs when occult retroperitoneal bleeding impinges on the appropriate nerve roots. The syndrome involves the acute onset of groin and thigh pain with characteristic flexion and external rotation of the hip. It may mimic other conditions such as acute arterial occlusion. Thorough knowledge of the anatomy of the femoral nerve explains the clinical features and leads the clinician to suspect the occurrence of this syndrome. Three cases have been reviewed that exhibited this condition as a result of retroperitoneal bleeding, a complication of systemic heparin therapy. The hemophilia that afflicted Alexis, the Crown Prince of Russia and son of Tsar Nicholas and Tsarina Alexandra, resulted in this clinical syndrome. The consequences enabled the sinister starets, Gregory Rasputin, to become intimately involved with the royal family, influencing the response of the Tsar to the political events in Russia, thereby playing an important role in setting the stage for the 1917 Russian communist revolution.
Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.
Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418
Singer, Daniel E; Hellkamp, Anne S; Piccini, Jonathan P; Mahaffey, Kenneth W; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L; Becker, Richard C; Breithardt, Günter; Hankey, Graeme J; Hacke, Werner; Nessel, Christopher C; Patel, Manesh R; Califf, Robert M; Fox, Keith A A
Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i-TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i-TTR was 55.2% (SD 21.3%) and the median i-TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i-TTR, dominant determinants were previous warfarin use (mean i-TTR of 61.1% for warfarin-experienced versus 47.4% in VKA-naïve patients) and geographic region where patients were managed (mean i-TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i-TTRs had INR distributions shifted toward lower INR values and had longer inter-INR test intervals. Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i-TTR in global studies of warfarin. Regional differences in mean i-TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. URL: ClinicalTrials.gov. Unique identifier: NCT00403767.
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.
Dakay, Katarina; Chang, Andrew D; Hemendinger, Morgan; Cutting, Shawna; McTaggart, Ryan A; Jayaraman, Mahesh V; Chu, Antony; Panda, Nikhil; Song, Christopher; Merkler, Alexander; Gialdini, Gino; Kummer, Benjamin; Lerario, Michael P; Kamel, Hooman; Elkind, Mitchell S V; Furie, Karen L; Yaghi, Shadi
Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation. We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe). We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16). LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Ko, Darae; Hylek, Elaine M
The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhage. Understanding the risks and their underlying mechanisms would help to mitigate adverse events and improve persistence with these life-saving therapies. The objectives of this review are to: (1) elucidate the age-related physiologic changes that render this high risk subgroup susceptible to hemorrhage, (2) identify mutable risk factors and hazards contributing to an increased bleeding risk in older individuals, and (3) discuss interventions to optimize anticoagulation therapy in this population.
Gleason, Lauren Jan; Friedman, Susan M
This article describes current literature and treatment plans for managing anticoagulation and antiplatelet agents in patients presenting with hip fractures. Indications for anticoagulation and antiplatelet agents are discussed, and management techniques for when patients present with hip fractures are reviewed.
... by heart Treatments + Tests What Are Anticoagulants and Antiplatelet Agents? Anticoagulants and antiplatelet agents are medicines that reduce blood clotting in an artery, a vein or the heart. Blood clots can block the ...
Barnes, Geoffrey D; Kanthi, Yogendra; Froehlich, James B
Initial treatment for venous thromboembolism (VTE) includes the acute and intermediate phases, usually lasting for 3 months. The choice to extend therapy beyond the initial 3-month window involves assessing a combination of risk factors for VTE recurrence and bleeding, along with weighing patient preferences. In some cases, such as VTE provoked by a reversible surgical risk factor, the recurrence risk is sufficiently low that most patients should not receive extended therapy. In other cases, such as VTE associated with malignancy, the recurrence risk is sufficiently high that treatment should be extended beyond the initial 3 months. However, a large number of patients fall into a grey zone where the decision on extended therapy is less clear-cut. In this review, we summarize the evidence for VTE recurrence risk and the role for extended anticoagulation given a variety of patient-specific factors and laboratory results. We also review the role of VTE risk prediction tools and provide a recommended algorithm for approaching the decision of extended anticoagulation therapy. Various agents available for extended VTE therapy, including warfarin, aspirin and the direct oral anticoagulant agents, are discussed. PMID:25832602
Antz, Matthias; Hullmann, Bettina; Neufert, Christian; Vocke, Wolfgang
The correct anticoagulation regimen for prevention of thromboembolic events is essential in patients with atrial fibrillation. However, only a minority of patients receives anticoagulation according to the guidelines. The current guidelines are intended to make the indication for anticoagulation more simple and are summarized in the present article. This includes recommendations for chronic anticoagulation, prevention of thromboembolic events after cardioversion and in ablation of atrial fibrillation.
King, Brian J; El-Azhary, Rokea A; McEvoy, Marian T; Shields, Raymond C; McBane, Robert D; McCarthy, James T; Davis, Mark D P
Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants. Patient data, including demographics, comorbidities, other treatments, and adverse events, were abstracted from the health records. Eleven patients (69%) had chronic kidney disease (stage ≥3A), and eight (50%) received dialysis. Apixaban was the most frequently used agent (n = 11 [69%]). Dabigatran (n = 4 [25%]) and rivaroxaban (n = 2 [13%]) were reserved for patients with mild renal impairment (stage ≤2). One clinically relevant but nonmajor bleeding event occurred. There were no major bleeding events. Nine patients (56%) were alive at last follow-up, and five (31%) had complete resolution of their calciphylaxis (mean follow-up, 523 days; range, 26-1884 days). DOACs were safe and well tolerated in patients with calciphylaxis, in this initial experience. Several patients had improvement or resolution of calciphylaxis in response to therapy that included DOACs. The degree of renal impairment should guide DOAC choice. Randomized trials are required to determine treatment efficacy. © 2017 The International Society of Dermatology.
Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John
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
Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud
Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.
Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.
Sarig, Galit; Garach-Jehoshua, Osnat; Deutch, Varda; Winder, Asher; Hyam, Esti; Katz, Ben Zion; Lahav, Judith; Cassel, Aliza; Zivelin, Ariella; Souroujon, Moshe; Shimron, Orit
Lupus anticoagulants (LAC) are antibodies which are detected by a prolongation of phospholipid-dependent coagulation assays, and are associated with thrombotic events and pregnancy complications in patients with the antiphospholipid syndrome. The antiphospholipid syndrome is defined by arterial or venous thrombosis and/or pregnancy morbidity and by laboratory diagnosis of antiphospholipid antibodies. The laboratory diagnosis is based on LAC and/or anticardiolipin and/or anti-beta2-glycoprotein I antibodies present in plasma, on two or more occasions at least 12 weeks apart. ALthough the presence of LAC correlates best with thrombosis, the Laboratory testing of LAC is not well standardized. In this article, the Laboratory evaluation of LAC will be explained, including the different tests that are recommended by the Israeli Sub-committee of Thrombosis and Hemostasis Laboratories, the possibility to evaluate LAC in patients treated with antithrombotic therapy, and how to report and interpret the results.
Engelsen, Jytte; Nielsen, Susan M; Thorsen, Sixtus
Severe hemorrhagic diathesis due to lupus anticoagulant complicated by hypoprothrombinaemia resulting from prothrombin autoantibodies is a rare disorder and is often associated with systemic lupus erythematosus (SLE). We report a case in which a 15-year-old girl with SLE developed marked haemorrhagic manifestations due to menorrhagia and nosebleeds. The acute bleeding episode was treated with SAGM, tranexamic acid and recombinant factor VIIa. Lupus anticoagulant, cardiolipin antibodies and antiprothrombin antibodies were successfully depressed within weeks after corticosteroid therapy was begun.
Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis.
Hijazi, Ziad; Hohnloser, Stefan H; Oldgren, Jonas; Andersson, Ulrika; Connolly, Stuart J; Eikelboom, John W; Ezekowitz, Michael D; Reilly, Paul A; Siegbahn, Agneta; Yusuf, Salim; Wallentin, Lars
Renal impairment increases the risk of stroke and bleeding in patients with atrial fibrillation. In the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, dabigatran, with ≈80% renal elimination, displayed superiority over warfarin for prevention of stroke and systemic embolism in the 150-mg dose and significantly less major bleeding in the 110-mg dose in 18 113 patients with nonvalvular atrial fibrillation. This prespecified study investigated these outcomes in relation to renal function. Glomerular filtration rate was estimated with the Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Modification of Diet in Renal Disease (MDRD) equations in all randomized patients with available creatinine at baseline (n=17 951), and cystatin C-based glomerular filtration rate was estimated in a subpopulation with measurements available (n=6190). A glomerular filtration rate ≥80, 50 to <80, and <50 mL/min was estimated in 32.6%, 47.6%, and 19.8% and in 21.6%, 59.6%, and 18.8% of patients based on Cockcroft-Gault and CKD-EPI, respectively. Rates of stroke or systemic embolism, major bleeding, and all-cause mortality increased as renal function decreased. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily compared with warfarin, without significant heterogeneity in subgroups defined by renal function (interaction P>0.1 for all). For the outcome of major bleeding, there were significant interactions between treatment and renal function according to CKD-EPI and MDRD equations, respectively (P<0.05). The relative reduction in major bleeding with either dabigatran dose compared with warfarin was greater in patients with glomerular filtration rate ≥80 mL/min. The efficacy of both dosages of dabigatran was consistent with the overall trial irrespective of renal function. However, with the CKD-EPI and MDRD equations, both dabigatran dosages displayed significantly lower
Rodríguez-Campello, A; Roquer-González, J; Gomis-Cortina, M; Munteis-Olivas, E; Ois-Santiago, A; Herraiz-Rocamora, J
Intracranial haemorrhage (ICH) during dicumarinic treatment is a complication related to anticoagulation intensity with a high level of mortality. The aim of our study is to analize etiology, location and outcome of intracerebral haemorrhages related with anticoagulant therapy. Over 401 spontaneous intracranial haemorrhages consecutively admitted in the neurological ward, we analyzed the acenocumarol ICH by location, anticoagulation range and factors that conditioned the outcome. We identified 26 patients, 6.5% of total ICH. Mean age was 75.2 +/- 7.9 years-old, over the rest of ICH. International Normalized Ratio (INR) was less than 2 in 10 patients, between 2 and 3 in six and greater than 3 in ten patients. 8 patients (31%) died, three of them had multiple ICH, but none of them had a INR greater than 2. Dicumarinic haemorrhages were of lobar location in 14 cases (three of them multiples) and deep in 12 cases. In our study, dicumarinic ICH are responsible of 6.5% total intracranial haemorrhages and they are not in clear relation with excessive anticoagulation. Mortality is slightly greater than the other ICH. Relatively benignity of these patients, the age and lobar location suggest that the etiology of these haemorrhages can be related to a subjacent amyloid angiopathy.
Mueller, Edward J.
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.
De Lorenzo, Ferruccio; Dotsenko, Olena; Scully, Michael F; Tymoshchuk, Myroslava
Thromboembolic events contribute significantly to the morbidity and mortality in cancer. Effective and safe anticoagulation - mainstay in prevention and treatment of thrombosis - remains very challenging clinical task in oncology patients - population of high rate of treatment failure, bleeding complications and thromboembolic events recurrences. Prospective randomized clinical studies have documented that with advent of low molecular weight heparins new possibilities for thrombosis treatment and long-term prevention with more convenient and safe anticoagulation have emerged. Considerable advances have been achieved at present time in our understanding of the pathobiology of thrombogenesis in human malignancies, particularly of the interactions between coagulation cascade reactions and processes of tumor growth and dissemination. This builds up a new challenge for modern oncology - appreciation of the hypothesis of anti-malignant effects of anticoagulants, which could influence the outcome of human cancer. Antineoplastic effects of antithrombotic drugs have been reported in various experimental models. Heparins have been the most extensively studied and have been shown to reduce the primary tumour growth and its metastatic spread. Joint evidence from fundamental research and from several randomized clinical trials, observing beneficial impact of low molecular weight heparins therapy on cancer patients survival, dictate the need for further scientific steps to confirm biological effects of heparins in human malignancies. The evidence is started to accumulate, that clinically approved heparins have different abilities to influence some processes of metastasis spread. The experimental work towards development of heparin derivates with low anticoagulant activity, but with potential inhibitory effects on tumor cells migration is in progress.
Ashjian, Peter; Chen, Constance M; Pusic, Andrea; Disa, Joseph J; Cordeiro, Peter G; Mehrara, Babak J
Numerous protocols exist to prevent thrombosis after free-tissue transfer. Many surgeons advocate using aspirin or other antiplatelet agents, but little objective evidence supports this practice. This study evaluates the rate of microvascular thrombosis in patients undergoing free-tissue transfer treated with or without antiplatelet agents. All consecutive free flaps from 2002-2005 at a single center were reviewed using a prospectively maintained database. Patients were in 2 groups based on postoperative anticoagulation administration. In group 1, 325 mg of aspirin was administered daily for 5 days postoperatively. In group 2, patients were treated with 5000 units of low-molecular-weight heparin (LMWH) per day until ambulating. Patient demographics, procedure type, diagnosis, adjuvant treatment, and procedure type were recorded. Outcome variables included microvascular thrombosis, partial or total flap loss, hematoma, bleeding, deep venous thrombosis (DVT), pulmonary embolism, and death. Four hundred seventy patients underwent 505 microvascular free flaps to reconstruct oncologic defects. Two hundred sixty flaps (group A) received postoperative aspirin therapy; 245 flaps (group B) received LMWH therapy. Both groups were statistically similar in their composition. No statistically significant difference was noted between the 2 groups when comparing outcome variables including microvascular thrombosis, partial or total flap loss, hematoma, bleeding, DVT, pulmonary embolism, and death. Postoperative anticoagulation choice has no statistically significant effect on the incidence of free flap complications, including bleeding, thromboembolism, and flap loss. We conclude that aspirin or LMWH therapy demonstrates equivalent outcomes when used as single-agent postoperative anticoagulation in oncologic free flap reconstruction.
Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip
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.
Carr, M M; Mason, R B
Today's trend toward ambulatory medical care will bring more pharmacological problems into the dental office. While the dental management of patients taking oral anticoagulants is controversial, current research supports the contention that they can be safely treated on an outpatient basis. The use of the International Normalized Ratio (INR) has made better estimates of prothrombin time possible, and patients can be maintained in a narrow therapeutic range. Postoperative hemorrhage can be avoided or controlled with local hemostatic agents.
Orfeo, Thomas; Butenas, Saulius; Brummel-Ziedins, Kathleen E.; Gissel, Matthew; Mann, Kenneth G.
Summary Background Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (f)Xa emerging as a promising approach. Objective To assess anticoagulant strategies targeting fXa. Methods A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole blood model) were used to evaluate clinically relevant examples of the two available types of fXa directed anticoagulants (an antithrombin (AT)-dependent agent, fondaparinux, and an AT-independent inhibitor, Rivaroxaban) in experimental regimens relevant to long term (suppression of new Tf-initiated events) and acute (suppression of ongoing coagulation processes) clinical applications. Results Computational representations of each anticoagulant’s efficacy in suppressing thrombin generation over a range of anticoagulant concentrations in both anticoagulation regimens were validated by results from corresponding empirical reconstructions and were consistent with those recommended for long term and acute clinical applications respectively. All three model systems suggested that Rivaroxaban would prove more effective in the suppression of an ongoing coagulation process than fondaparinux, reflecting its much higher reactivity toward the prothrombinase complex. Conclusion The success of fondaparinux in acute settings in vivo is not explained solely by its properties as an fXa inhibitor. We have reported that fIXa contributes to the long term capacity of clot-associated catalysts to restart a coagulation process [Orfeo T et al. J Biol Chem 2008;283:9776], suggesting that the enhanced anti-fIXa activity of fondaparinux-AT may be critical to its success in acute settings in vivo. PMID:20492473
Ten Cate, Hugo
New oral anticoagulants (NOACs) have been introduced to improve anticoagulant therapy worldwide, but safe implementation may require additional measures. First, optimization of dose adjustment based on therapeutic levels of the drug may be more appropriate than fixed dose therapy. The development and implementation in quantitative laboratory assays will enable further dose optimization. Second, non-adherence to medication is a potential threat to the safe use of NOACs. Since cardiovascular medication may not be optimally used in about 50% of patients, procedures to improve adherence are imperative, also for NOAC therapy and in particular in elderly patients.
Akl, Elie A; Kahale, Lara A; Hakoum, Maram B; Matar, Charbel F; Sperati, Francesca; Barba, Maddalena; Yosuico, Victor E D; Terrenato, Irene; Synnot, Anneliese; Schünemann, Holger
Anticoagulation may improve survival in patients with cancer through a speculated anti-tumour effect, in addition to the antithrombotic effect, although may increase the risk of bleeding. To evaluate the efficacy and safety of parenteral anticoagulants in ambulatory patients with cancer who, typically, are undergoing chemotherapy, hormonal therapy, immunotherapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. A comprehensive search included (1) a major electronic search (February 2016) of the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), MEDLINE (1946 to February 2016; accessed via OVID) and Embase (1980 to February 2016; accessed via OVID); (2) handsearching of conference proceedings; (3) checking of references of included studies; (4) use of the 'related citation' feature in PubMed and (5) a search for ongoing studies in trial registries. As part of the living systematic review approach, we are running searches continually and we will incorporate new evidence rapidly after it is identified. This update of the systematic review is based on the findings of a literature search conducted on 14 August, 2017. Randomized controlled trials (RCTs) assessing the benefits and harms of parenteral anticoagulation in ambulatory patients with cancer. Typically, these patients are undergoing chemotherapy, hormonal therapy, immunotherapy or radiotherapy, but otherwise have no standard therapeutic or prophylactic indication for anticoagulation. Using a standardized form we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interested included all-cause mortality, symptomatic venous thromboembolism (VTE), symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, minor bleeding, and quality of life. We assessed the certainty of evidence for each outcome using the GRADE approach
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).
Greenway, Anthea; Ignjatovic, Vera; Summerhayes, Robyn; Newall, Fiona; Burgess, Janet; DeRosa, Lydia; Monagle, Paul
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.
Heng, Charles; Rybarczyk-Vigouret, Marie Christine; Michel, Bruno
A growing number of patients today receive anticoagulants. These drugs can cause serious adverse reactions leading to patients' hospitalization. The present study aimed to assess the number of hospital admissions as a result of anticoagulant adverse reactions in Alsace, a French region of 1.8 million inhabitants, and to estimate the economic burden associated with their management. A retrospective analysis was performed using data extracted from the regional and anonymous hospital Programme de Médicalisation des Systèmes d'Information (PMSI) database to assess the number of hospital admissions and the associated costs. Stays from public and private hospitals were extracted from the database using two International Classification of Diseases, 10th revision, codes referring to anticoagulant drugs: 'T45.5-Poisoning by anticoagulants' and 'Y44.2-Anticoagulants' adverse effect in therapeutic use'. Costs were calculated from official French tariffs. Within a 2-year period from 1 Januray 2010 to 31 December 2011, 462 anticoagulant-related hospital admissions, predominantly in elderly patients, were identified in Alsace. These stays, as a result of anticoagulant adverse reactions, represented a cost of 2 050 127.86 euros (including hospitalization and expensive drugs). Regional PMSI database constitutes an effective tool to explore anticoagulant-related hospital admissions. Based on our study, one can state that the cost of anticoagulation therapies lies not only in the price of the drugs but also in the cost of adverse reaction management. Policy makers should be aware of this reality and should focus on better medication supervision in order to improve patient safety and reduce expenses. Copyright © 2014 John Wiley & Sons, Ltd.
Mendenhall, V.M.; Pank, L.F.
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
Pototski, Mariele; Amenábar, José M
Antiplatelet and anticoagulant agents have been extensively researched and developed as potential therapies in the prevention and management of arterial and venous thrombosis. On the other hand, antiplatelet and anticoagulant drugs have also been associated with an increase in the bleeding time and risk of postoperative hemorrhage. Because of this, some dentists still recommend the patient to stop the therapy for at least 3 days before any oral surgical procedure. However, stopping the use of these drugs exposes the patient to vascular problems, with the potential for significant morbidity. This article reviews the main antiplatelet and anticoagulant drugs in use today and explains the dental management of patients on these drugs, when subjected to minor oral surgery procedures. It can be concluded that the optimal INR value for dental surgical procedures is 2.5 because it minimizes the risk of either hemorrhage or thromboembolism. Nevertheless, minor oral surgical procedures, such as biopsies, tooth extraction and periodontal surgery, can safely be done with an INR lower than 4.0.
Mohammed, Shaban; Aljundi, Amer H. S.; Kasem, Mohamed; Alhashemi, Mohammed; El-Menyar, Ayman
There is a limited knowledge about the predictors of anticoagulation control in patients with nonvalvular atrial fibrillation (NVAF). Furthermore, few reports addressed the role of time in therapeutic range (TTR) that could reflect the safety and efficacy of anticoagulation therapy. We aimed to assess factors that affect the quality of anticoagulation therapy utilizing TTR in patients with NVAF. A retrospective observational study was conducted for patients with NVAF who were maintained on warfarin >6 months at a tertiary cardiac care hospital. Patients were categorized according to the TTR status (≥65% vs. <65%). A total of 241 eligible patients were identified. A high-quality anticoagulation based on TTR values ≥65% was found in 157 (65.1%) patients; the remaining (34.9%) patients represented the low-quality anticoagulation group (TTR <65%). Demographics and clinical characteristics were comparable in the two TTR groups. Both groups were comparable in terms of warfarin dose and medications use. When compared to patients with high-quality anticoagulation, patients in the low-quality anticoagulation group were more likely to seek outpatient warfarin clinic visits more frequently (22.3 ± 5.5 vs. 18 ± 4.4, P = 0.001) and to have higher rate of polypharmacy (57.1% vs. 42%, P = 0.03). Of note, patients in both groups had similar major bleeding events (P = 0.41). After adjusting for age and sex, polypharmacy use was a predictor of poor coagulation control (odds ratio = 1.89, 95% confidence interval: 1.03–3.33; P = 0.03). In NVAF patients, TTR is generally high in our cohort. Patients with polypharmacy and frequent clinic visits have lower TTR. High-quality oral anticoagulation could be achieved through optimizing TTR without a significant risk of major bleeding. PMID:28217549
Shifting Perceptions of Risk and Reward: Use of Anticoagulation in Patients With Acute Brain Ischemia and Atrial Fibrillation: Nine-Year Data From a National Acute Stroke Registry (National Acute Stroke Israeli Survey [NASIS]).
Schwammenthal, Yvonne; Tsabari, Rakefet; Orion, David; Merzlyak, Oleg; Haratz, Salo; Peretz, Shlomi; Bornstein, Natan M; Ifergane, Gal; Einhorn, Michal; Schwammenthal, Ehud; Geva, Diklah; Tanne, David
Despite overwhelming evidence for the benefits of anticoagulation in patients with brain ischemia and atrial fibrillation, vast underuse has been reported. Use of anticoagulation for secondary stroke prevention was assessed in the National Acute Stroke Israeli Survey registry (NASIS) of hospitalized patients with atrial fibrillation and acute brain ischemia. Logistic regression analysis was performed to evaluate the effects of clinical covariates on anticoagulation therapy at discharge, and anticoagulation use over time was assessed in subgroups of patients with identified barriers to anticoagulation utilization. There were 1254 survivors of acute brain ischemia with atrial fibrillation (mean age 77.2±10.6 years; 57.7% female). Between 2004 and 2013, the proportion of patients discharged on anticoagulation increased from 55% to 76.2%, and among those without perceived contraindications from 70% to 96% (P<0.0001). Older age, greater stroke severity, earlier registry period, and presence of contraindications were independent predictors of withholding therapy. Increased anticoagulation use over the years was observed even in patients with barriers to anticoagulation use, including patients with potential contraindications (P<0.001). In survivors of acute brain ischemia with atrial fibrillation, we observed a substantial increase in anticoagulation utilization within less than a decade. This change was mainly driven by greater utilization of anticoagulation in subgroups with traditional clinical barriers to anticoagulation use, indicating a shift in physicians' perceptions of the risk-benefit ratio of anticoagulation. © 2017 American Heart Association, Inc.
Garcia, David A
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.
Tauron, M; Paniagua, P; Muñoz-Guijosa, C; Mirabet, S; Padró, J M
Heparin-induced thrombopenia is a common autoimmune complication. It is a prothrombotic state due to the formation of antibodies against heparin/platelet factor 4 complexes. In this situation drugs other than heparin must be used for anticoagulation during extracorporeal circulation (bypass) surgery. Two cases of heart transplantation are presented in whom bivalirudin was used as an anticoagulant during the cardiopulmonary bypass. Severe bleeding complications were observed in both patients. The diagnosis of heparin-induced thrombopenia needs to be improved, as well as the development of protocols for using new drugs other than heparin. For this reason, we have reviewed current protocols and alternative therapies to heparin. Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.
Shamoun, Fadi; Obeid, Hiba; Ramakrishna, Harish
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
... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...
Della Valle, Antonio; Sammartino, Gilberto; Marenzi, Gaetano; Tia, Mariano; Espedito di Lauro, Alessandro; Ferrari, Francesca; Lo Muzio, Lorenzo
This study evaluated the effectiveness of a protocol using platelet-rich plasma (PRP) to prevent bleeding after dental extraction in patients treated with anticoagulant oral therapy. Forty patients with mechanical heart-value replacement who were treated with anticoagulant oral therapy were selected for the study. Each patient was treated with PRP gel placed into residual alveolar bone after extraction without heparin administration after suspension of oral anticoagulant drugs (36 hours). Only 2 patients reported hemorrhagic complications (5%). Sixteen patients (40%) had mild bleeding that was easy to control with hemostatic topical agents; this mild bleeding terminated completely 1 to 3 days after the surgical procedures. The remaining 22 patients (55%) presented with adequate hemostasis. Oral surgery in heart surgical patients under oral anticoagulant therapy may be facilitated with PRP gel. Its use is an advanced and safe procedure. This biological and therapeutical improvement can simplify systemic management and help avoid hemorrhagic and/or thromboembolic complications.
Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Barón-Franco, Bosco; Murcia-Zaragoza, José; Fuertes Martín, Aurelio; Alemán, Antonio; Ollero-Baturone, Manuel
To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.
Jones, Kellie L; Barnett, Chad; Gauthier, Michelle; Boster, Bonnie; Espirito, Janet L; Michaud, Laura B
Report descriptive outcome measures related to the quality of pharmacist-managed anticoagulation care with warfarin in patients with breast cancer since the formation of the anticoagulation management service (AMS). Retrospective review of 145 patients with breast cancer (median age 54 years) receiving warfarin therapy for venous thromboembolism (VTE) managed by the pharmacist-run AMS between 1998 and 2005. The median time followed by the AMS was 151 days. Fifty three percent (n = 1651) of total lab draws (n = 3129) were within the target therapeutic INR range 2-3. Recurrent thrombosis occurred in 4.1% of patients. Minor bleeding occurred in 18.6% of patients and major bleeding occurred in three patients (2.1%, gastrointestinal, intra-abdominal, and subdural hematoma). To date, this is the largest known published database of cancer patients receiving anticoagulation in a pharmacist-managed anticoagulation service. Recurrent VTE rates, major and minor bleeding rates, and percentage of time spent within the therapeutic range are slightly different in our patient population compared to an oncology population receiving warfarin and a non-oncology population with warfarin managed by AMS. Oral anticoagulation with warfarin is an effective, albeit complicated, treatment for venous thromboembolism in the oncology population. Although low-molecular weight heparin (LMWH) therapy is now the preferred treatment for thrombosis in malignancy, warfarin is still relevant in patients who are unable to receive treatment with LMWH. This report provides valuable information supporting coordinated anticoagulation therapy with a pharmacist-managed service in a breast cancer-specific population, and contributes to the growing data supporting the challenging nature of maintaining warfarin anticoagulation in patients with cancer.
Gianetti, J; Gensini, G; De Caterina, R
The recent publication of two large trials of secondary prevention of coronary artery disease with oral anticoagulants (WARIS and ASPECT) has caused a revival of the interest for this antithrombotic therapy in a clinical setting where the use of aspirin is common medical practice. Despite this, the preferential use of aspirin has been supported by an American cost-effectiveness analysis (JAMA 1995; 273: 965). Using the same parameters used in that analysis and incidence of events from the Antiplatelet Trialists Collaboration and the ASPECT study, we re-evaluated the economic odds in favor of aspirin or oral anticoagulants in the Italian Health System, which differs significantly in cost allocation from the United States system and is, conversely, similar to other European settings. Recalculated costs associated with each therapy were 2,150 ECU/ patient/year for oral anticoagulants and 2,187 ECU/patient/year for aspirin. In our analysis, the higher costs of oral anticoagulants versus aspirin due to a moderate excess of bleeding (about 10 ECU/ patient/year) and the monitoring of therapy (168 ECU/ patient/year) are more than offset by an alleged savings for recurrent ischemic syndromes and interventional procedures (249 ECU/ patient/year). Preference of aspirin vs. oral anticoagulants in a pharmaco-economical perspective is highly dependent on the geographical situation whereupon calculations are based. On a pure cost-effectiveness basis, and in the absence of data of direct comparisons between aspirin alone versus I.N.R.-adjusted oral anticoagulants, the latter are not more expensive than aspirin in Italy and, by cost comparisons, in other European countries in the setting of post-myocardial infarction.
Hall, Deanne; Buchanan, Julianne; Helms, Bethany; Eberts, Matthew; Mark, Scott; Manolis, Chronis; Peele, Pamela; Docimo, Anne
To evaluate the differences in health care expenditures and therapeutic outcomes of patients receiving warfarin therapy management by a pharmacist-managed anticoagulation service compared with those receiving warfarin management by usual medical care. Retrospective, matched-cohort study. University of Pittsburgh Medical Center (UPMC) and UPMC Health Plan. Three hundred fifty adults who received warfarin therapy; 175 were managed by the pharmacist-managed anticoagulation service for at least 2 months between October 1, 2007, and September 30, 2008, (case patients) and 175 received usual care (matched comparison group). Medical claims data compared were direct anticoagulation cost and overall medical care costs, anticoagulation-related adverse events, hospitalizations and emergency department visits, frequency of international normalized ratio (INR) testing, and quantity of warfarin refills. Operational costs of the anticoagulation service were also calculated. The INR values and time within therapeutic range were assessed through anticoagulation service reports and laboratory results. The direct anticoagulation care cost was $35,465 versus $111,586 and the overall medical care cost was $754,191 versus $1,480,661 for the anticoagulation service group versus the usual care group. Accounting for operational and drug expenditure costs, the cost savings was $647,024 for the anticoagulation service group. The anticoagulation service group had significantly fewer anticoagulation-related adverse events (14 vs 41, p<0.0001), hospital admissions (3 vs 14, p<0.00001), and emergency department visits (58 vs 134, p<0.00001). The percentage of INR values in range and the percentage of time the INR values were in range were significantly higher in the anticoagulation service group (67.2% vs 54.6%, p<0.0001, and 73.7% vs 61.3%, p<0.0001, respectively). Compared with the usual care group, the anticoagulation service group had significantly more INR tests performed but demonstrated
Xu, Tingting; Peng, Fang; Zhang, Tao; Chi, Bo; Xu, Hong; Mao, Chun; Feng, Shuaihui
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.
Sniecinski, Roman M; Levy, Jerrold H
The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass. Copyright © 2015 Elsevier Ltd. All rights reserved.
... 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 ...
... 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 ...
MIRANDA, M.; MARTINEZ, L.S.; FRANCO, R.; FORTE, V.; BARLATTANI, A.; BOLLERO, P.
SUMMARY The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant – dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) – have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions. PMID:28042443
Miranda, M; Martinez, L S; Franco, R; Forte, V; Barlattani, A; Bollero, P
The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions.
Shah, Karna; Bayoumi, Riad; Banerjee, Yajnavalka
Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure-activity relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF-FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.
New oral anticoagulants (NOAC) are increasingly applied after hip and knee replacement and in patients with non-vavular atrial fibrillation. Patients with cardiac disease benefit from regional anaesthesia, especially catheter-provided postoperative pain relief, but are at higher risk for puncture-related haematoma when NOAC are applied simultaneously. Therefore recommended time intervals between drug application and performance of RA including catheter removal of 22-34 h must be respected. The next dose of NOAC must not be given before 6 h have been elapsed; after bloody tap a delay of 24 h is recommended. The respective time intervals are prolonged in patients with renal insufficiency, especially when Dabigatran is applied, until 36 to 72 h. In general, high risk patients with NOAC undergoing surgery benefit from an interdicsciplinary approach and from less traumatic techniques such as spinal anaesthesia or superficial peripheral nerve blocks. © Georg Thieme Verlag Stuttgart · New York.
da Silva, Rose M.F.L.
Atrial fibrillation is the most frequent arrhythmia in clinical practice, reaching 2% of the people in the world and is associated with systemic embolism. Thus, the use of anticoagulants is indicated if CHA2DS2-VASc score ≥2 or in patients with previous transient ischemic attack or stroke. For decades, warfarin, a vitamin K antagonist, was the only choice for chronic oral anticoagulation. Recently, novel oral anticoagulants (NOACs) have been introduced, offering similar (or better) effectiveness, safety, and convenience to the vitamin K antagonists. Dabigatran was the first NOAC approved and is a direct thrombin inhibitor. Rivaroxaban and apixaban are factor Xa inhibitors. They display rapid onset of action, more predictable of pharmacological profile, less interactions with other drugs, lack of significant effects in the diet, and less risk of intracranial hemorrhage than warfarin. Despite that dose adjustment is necessary for patients with chronic kidney disease or according to body weight, these new drugs do not require regular monitoring. There are recommendations for the start and follow-up therapy with NOACs, planning for cardioversion, ablation and surgical interventions and the management of bleeding. This article is a review of the major studies of the NOACs. The clinical use of these drugs in patients with non-valvular atrial fibrillation is presented. PMID:25470147
Gu, Kang Mo; Shin, Jong Wook; Park, In Won
Antiphospholipid syndrome (APS) is an acquired systemic autoimmune disorder characterized by a combination of clinical criteria, including vascular thrombosis or pregnancy morbidity and elevated antiphospholipid antibody titers. It is one of the causes of deep vein thrombosis and pulmonary embolism that can be critical due to the mortality risk. Overall recurrence of thromboembolism is very low with adequate anticoagulation prophylaxis. The most effective treatment to prevent recurrent thrombosis is long-term anticoagulation. We report on a 17-year-old male with APS, who manifested blue toe syndrome, deep vein thrombosis, pulmonary thromboembolism, and cerebral infarction despite adequate long-term anticoagulation therapy.
Atrial fibrillation treatment relies on anticoagulation therapy that reduces the risk of stroke. Vitamin K antagonists (VKA) were the only oral anticoagulant drugs for more than 50 years, but they are difficult to manage especially in the elderly. In France, VKA are the main cause of iatrogenic hospitalizations with about 17,000 hospitalizations per year and around 4,000 to 5,000 deaths per year. Pharmacologic properties of VKA, especially the narrow therapeutic margin explain the complexity of their management. Several studies have shown that patients treated with VKA were on average only 50% of the time with an INR in the therapeutic range. In other words, patients are, half of the time, either-under treated or over-treated. Within this framework, development of new oral anticoagulant drugs appeared necessary, in order to obtain drugs with larger therapeutic margin and a better risk/benefit profile than VKA. Three large randomized clinical trials including almost 50,000 patients with 20,000 subjects over 75 years old and 8,000 over 80 years old, show a better risk/benefit profile of the new oral anticoagulants (NOAC) than VKA, characterized by a 50% reduction of cerebral hemorrhages, 22% reduction of stroke and 12% reduction of total mortality. Meanwhile, their renal elimination and the lack of control of the biological efficacy need to be taken into account for their prescription. Renal failure (estimated glomerular filtration rate according to Cockcroft formula < 30 mL/min) contraindicates their use. Their half-life is shorter than that of VKA and the biological monitoring is not available, thus a good adherence to the treatment is important. Studies specifically conducted among geriatric older population with poly-pathologies and frail are therefore needed to evaluate tolerance of NOAC in real life conditions.
Cundiff, David Keith
Context I coauthored a published review of anticoagulation for venous thromboembolism in the Cochrane Database of Systematic Reviews and published a review on the same topic in MedGenMed (now the Medscape Journal of Medicine). In contrast to the article in Medscape, the discussion and conclusions in the Cochrane review were altered appreciably during the review process. Consequently, I decided to critique all anticoagulation drug-related reviews and protocols in the Cochrane database with feedback letters concerning any issues of potential controversy. Evidence Acquisition Using key words in the search engine of the Cochrane Reviews, I located reviews and protocols involving anticoagulant drugs. I critiqued each anticoagulation review and protocol and sent a total of 57 feedback letters to Cochrane concerning each publication to elicit a response/rebuttal from the authors. Evidence Synthesis Cochrane anticoagulation review editors acknowledged receipt of all letters. As of 12 months after receipt of my last letter, the Cochrane authors have replied to 13 of the 57 and agreed with many of my points. Two protocols were withdrawn after my feedback letters were acknowledged. The 58 Cochrane anticoagulation drug reviews, including mine, contained 9 categories of methodological errors (207 total instances) and 4 types of biases (18 total instances). This review of those Cochrane reviews suggests that the effectiveness of anticoagulants for 30 medical indications is questionable. Conclusions The efficacy of anticoagulants for treatment and prophylaxis for 30 current medical indications should be reconsidered by the scientific community and medical regulatory agencies. At least 50,000 people per year worldwide have fatal bleeding due to anticoagulant treatment or prophylaxis for these indications. PMID:19295926
Nagata, Naoyoshi; Sakurai, Toshiyuki; Moriyasu, Shiori; Shimbo, Takuro; Okubo, Hidetaka; Watanabe, Kazuhiro; Yokoi, Chizu; Yanase, Mikio; Akiyama, Junichi; Uemura, Naomi
Anticoagulant management of acute gastrointestinal bleeding (GIB) during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB. Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs) and warfarin users. Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR) ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users. Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption) were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.
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
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; e.g., 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 (e.g., those with renal impairment) and other specific clinical situations.
Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide–polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants. PMID:25119520
Nutescu, Edith; Chuatrisorn, Ittiporn; Hellenbart, Erika
Clinicians and patients around the world have been intrigued by the concept of developing an oral anticoagulant with a broad therapeutic window and few drug and dietary interactions that can be administered at fixed doses with no or minimal monitoring. The recently approved oral direct thrombin inhibitor dabigatran, along with the emerging oral anti-factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have been developed to address many of the shortcomings of warfarin therapy. As warfarin is associated with extensive food and drug interactions, there is also a need to consider such interactions with the new oral anticoagulants. While to date few drug and dietary interactions have been reported with the new oral anticoagulants, it is still early in their development and clinical use cycle. Pharmacokinetic and pharmacodynamic profiles will have to be closely accounted for when determining the likelihood of a potential drug interaction prior to therapy initiation. As the list of drugs and supplements that interact with warfarin is continuously expanding, and the knowledge on drug interactions with the novel oral anticoagulants is still in its infancy, clinicians need to be vigilant when initiating any of these agents or when any changes in the patient's medication profile occur and perform a close screening for potential drug and dietary interactions. The objective of this paper is to give an update on drug and dietary interactions with warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban.
Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K
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.
Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068
Douketis, James D.; Spyropoulos, Alex C.; Kaatz, Scott; Becker, Richard C.; Caprini, Joseph A.; Dunn, Andrew S.; Garcia, David A.; Jacobson, Alan; Jaffer, Amir K.; Kong, David F.; Schulman, Sam; Turpie, Alexander G.G.; Hasselblad, Vic; Ortel, Thomas L.
BACKGROUND It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. METHODS We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. RESULTS In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], −0.6 to 0.8; P = 0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P = 0.005 for superiority). CONCLUSIONS In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to
Douketis, James D; Spyropoulos, Alex C; Kaatz, Scott; Becker, Richard C; Caprini, Joseph A; Dunn, Andrew S; Garcia, David A; Jacobson, Alan; Jaffer, Amir K; Kong, David F; Schulman, Sam; Turpie, Alexander G G; Hasselblad, Vic; Ortel, Thomas L
It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding. We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding. In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low
Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial.
Takizawa, Shunya; Tanaka, Fumiaki; Nishiyama, Kazutoshi; Hasegawa, Yasuhiro; Nagata, Eiichiro; Mizuma, Atsushi; Yutani, Sachiko; Nakayama, Taira; Kobayashi, Hiroyuki; Yanagimachi, Noriharu; Okazaki, Takashi; Kitagawa, Kazuo
Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs). This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(∗)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Zeus, Tobias; Kelm, Malte; Bode, Christoph
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.
Koenig-Oberhuber, V; Filipovic, M
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.
Knapp, Georgia L; Chalasani, Venu; Woo, Henry H
To compare perioperative factors and adverse events (AEs) in men undergoing photoselective vaporisation of the prostate (PVP) with or without continued anticoagulation therapy. Retrospective review of a PVP database of men treated with the 180-W lithium triborate (LBO) laser from 2010 to 2016. Of 373 men, 59 underwent PVP with continued anticoagulant therapy, which was defined as treatment with heparin, warfarin, clopidogrel, dipyridamol or new oral anticoagulant drugs. Perioperative factors and AEs occurring within 90 days of surgery were analysed. There was no statistically significant difference in the overall incidence of perioperative AEs between those receiving and not receiving anticoagulation therapy (30.5% vs 19.9%, P = 0.07). However, there was a statistically significant difference in the incidence of high-grade Clavien-Dindo events in men who continued anticoagulation during PVP (P = 0.01). No men required blood transfusion. There was no difference in operative times and energy utilisation between the groups. In all, 53 of the 59 men in the anticoagulation group had a high-grade American Society of Anesthesiologists score, compared to 27 of the 272 men in the control group. The anticoagulation group were also significantly older. The anticoagulation group had a significantly longer length of hospital stay and duration of catheterisation compared to the controls. While continued anticoagulation therapy is not associated with an overall increase in perioperative AEs, it is associated with an increased rate of high-grade Clavien-Dindo events. The findings of this study suggest that there should be caution in extrapolating results about the safety profile of earlier generation lasers to the current 180-W LBO laser for patients on anticoagulation. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.
Mattle, H; Kohler, S; Huber, P; Rohner, M; Steinsiepe, K F
From January 1981 to June 1986 116 patients with anticoagulation-related intracranial haemorrhage were referred to hospital. Seventy six of these haemorrhages were extracerebral, 69 were in the subdural and seven in the subarachnoid space. No epidural haemorrhages were identified. Compared with non-anticoagulation-related haematomas, the risk of haemorrhage was calculated to be increased fourfold in men and thirteenfold in women. An acute subdural haematoma, mostly due to contusion, was more frequently accompanied by an additional intracerebral haematoma than a chronic subdural haematoma. Trauma was a more important factor in acute subdural haematomas than in chronic. Almost half of the patients (48%) had a history of hypertension, more than a third (35%) had heart disease and about one fifth (18%) were diabetic. Headache was the most frequent initial symptom. Later decreased level of consciousness and focal neurological signs exceeded the frequency of headache. Three patients with subarachnoid haemorrhage and nine patients with acute subdural haematomas died, while those with chronic subdural haematomas all survived and had at the most mild, non-disabling sequelae. Myocardial infarction (22%), pulmonary embolism (20%), and arterial disease (20%) were the most frequent reasons for anticoagulant treatment. Critical review based on established criteria for anticoagulation treatment suggests there was no medical reason to treat a third of these patients. The single most useful measure that could be taken to reduce the risk of anticoagulation-induced intracranial haemorrhage would be to identify patients who are being unnecessarily treated and to discontinue anticoagulants. PMID:2769275
Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu
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
Rentea, Rebecca M.; Fehring, Charles H.
Causes of colonic and recto-sigmoid hematomas are multifactorial. Patients can present with a combination of dropping hemoglobin, bowel obstruction and perforation. Computed tomography imaging can provide clues to a diagnosis of intramural hematoma. We present a case of rectal hematoma and a review of current management literature. A 72-year-old male on therapeutic anticoagulation for a pulmonary embolism, was administered an enema resulting in severe abdominal pain unresponsive to blood transfusion. A sigmoid colectomy with end colostomy was performed. Although rare, colonic and recto-sigmoid hematomas should be considered as a possible diagnosis for adults with abdominal pain on anticoagulant therapy. PMID:28108634
Yanik, Megan V; Irvin, Marguerite R; Beasley, T Mark; Jacobson, Pamala A; Julian, Bruce A; Limdi, Nita A
To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non-KTRs). Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first-time warfarin users followed at two anticoagulation clinics. Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals. Adults aged 20 years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2-3 who were kidney transplant recipients (n=65) or patients without kidney transplants (n=1630). Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6 mg/day, p=0.0005) compared with non-KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non-KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR ≥ 60%) was low in both groups, it was similar among KTRs and non-KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors. KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Beynon, Christopher; Jakobs, Martin; Rizos, Timolaos; Unterberg, Andreas W; Sakowitz, Oliver W
With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. The POC coagulometer CoaguChek XS(®) was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37-61 min). Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.
De Vos, J; Hombrouckx, R
Several patients with heparin intolerance were dialysed with tri-sodium citrate as anticoagulant without acute clinical problems (good tolerance). After some weeks however problems arose. In all patients an alkalosis developed: the pre dialysis bicarbonate level rose progressively from 27 mmol/l to 40 mmol/l. This could be tempered by lowering the dialysis fluid bicarbonate concentration from 37 mmol/l to 25 mmol/l. A second problem was a progressive rise in pre dialysis sodium level from a mean of 136 mmol/l to 150 mmol/l. Adapting the dialysis fluid sodium concentration from 140 mmol/l towards 132 mmol/l could solve this. The third problem was a progressive rise in serum aluminium level in patients from 3 microg/l to 38 microg/l. After excluding water, concentrate, dialysis fluid, drug intake, etc... as possible sources, we controlled the aluminium level in the glass bottle containing tri-sodium citrate. We noted the very high value of 35,300 microg/l. After replacing the glass bottles with polyvinylchloride bags with a negligible aluminium content, the serum aluminium levels returned back to normal. It is known that citrate chelates the aluminium present in the glass of bottles or vials.
Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D
Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
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
Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo
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.
Norris, John W
There are no reliable data from randomised trials to decide whether anticoagulants or antiplatelet agents are better to prevent further thromboembolic events after cervical arterial dissection. Most neurologists favour anticoagulants based on the underlying pathology and the likely course of acute post-dissection thromboembolism.
Lobos-Bejarano, José M; Barrios, Vivencio; Polo-García, José; Escobar, Carlos; Vargas-Ortega, Diego; Marín-Montañés, Nuria; Prieto-Valiente, Luis; Fuentes, Sonia; Prieto, Miguel Angel; García-Ortiz, Luis
To assess the major clinical factors affecting the quality of anticoagulation and evaluate the predictive value of the SAMe-TT2R2 score to identify patients who will achieve a high average time in therapeutic range (T.T.R.) with vitamin K antagonist (V.K.A.) treatment. This observational, cross-sectional, retrospective and nationwide multicenter study included 1524 patients from the primary care setting with non-valvular atrial fibrillation receiving V.K.A. (≥12 months). We performed a bivariate analysis to identify factors individually associated with the T.T.R. and a multiple regression analysis to identify the independent predictive factors. For the validation of the SAMe-TT2R2 score, the receiver operating characteristic (R.O.C.) curve was calculated and the Hosmer-Lemeshow test was used to test calibration. A total of 94.8% of patients received acenocumarol (4.8% warfarin). A progressive decrease in mean T.T.R. was found when the SAMe-TT2R2 score increased from 0 points (72.1 ± 17.1%) to 4 points (64.1 ± 23.2%), p < 0.001. Other risk scores (CHADS2 and CHA2DS2-VASc, HAS-BLED) were also associated with the mean T.T.R. We found a significant association between low T.T.R. and the following clinical factors: female sex, three or more comorbidities, amiodarone treatment, dietary habits, bleeding history and the intake of ≥7 tablets per day besides V.K.A. (p < 0.01). Regarding SAMe-TT2R2 score validation, the R.O.C. curve showed significant capability, although not high, of discriminating good anticoagulation control (T.T.R. ≥65%) with an area under the curve of 0.562 (95% C.I. 0.533-0.592, p < 0.001) which increased, remaining modest, to 0.594 (95% C.I. 0.564-0.624, p < 0.001) when the factors not included in SAMe-TT2R2 score were added. In this cohort, the SAMe-TT2R2 score had a significant, although modest, ability to assess the likelihood of good international normalized ration (I.N.R.) control, and its predictive value might
Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID:27413710
Murray, Maureen; Tseng, Florina
Anticoagulant rodenticides inhibit the activation of vitamin K-ependent clotting factors, resulting in fatal hemorrhage. Nontarget species are exposed to these rodenticides primarily by direct consumption of baits or secondarily by consumption of poisoned prey. The diagnosis of anticoagulant rodenticide toxicosis is more challenging in birds than in mammals because of the limited availability of laboratory tests to evaluate avian coagulation. In addition, the presenting signs in birds may differ from those commonly seen in mammals. Treatment for acute blood loss and therapy with vitamin K1 can result in a favorable outcome in birds. This report describes the presenting signs, diagnosis, and successful treatment of a red-tailed hawk (Buteo jamaicensis) with secondary anticoagulant rodenticide toxicosis.
Mező, Erika; Eszenyi, Dániel; Varga, Eszter; Herczeg, Mihály; Borbás, Anikó
Heparin-based anticoagulants are drugs of choice in the therapy and prophylaxis of thromboembolic diseases. Idraparinux is a synthetic anticoagulant pentasaccharide based on the heparin antithrombin-binding domain. In the frame of our ongoing research aimed at the synthesis of sulfonic acid-containing heparinoid anticoagulants, we elaborated a modular pathway to obtain a series of idraparinux-analogue pentasaccharides bearing one or two primary sulfonic acid moieties. Five protected pentasaccharides with different C-sulfonation patterns were prepared by two subsequent glycosylation reactions, respectively, using two monosaccharide and four disaccharide building blocks. Transformation of the protected derivatives into the fully O-sulfated, O-methylated sulfonic acid end-products was also studied.
Henriksen, Jakob Nørgaard; Nielsen, Lars Peter; Hellebek, Annemarie; Poulsen, Birgitte Klindt
Reporting of adverse incidents is mandatory in Denmark. All reported adverse incidents are made anonymously, and stored in an encrypted database. It is the purpose of this descriptive study to describe the severity of adverse medication incidents caused by oral anticoagulants in hospitals. All moderate, severe and fatal reports concerning non-vitamin K antagonist oral anticoagulants were analyzed from date of marketing until July 8 2014. The data collection for warfarin was from January 1 2014 until July 8 2014. Three independent specialists in clinical pharmacology evaluated the severity of incident outcomes. A total of 147 adverse medication incidents were analyzed, and showed that de facto or potentially fatal and serious incidents were most frequently associated with sector change (admission to or discharge from hospital, or undergoing surgery) and resulted from insufficient or excess dosing. Physicians should be aware when prescribing and changing anticoagulant therapy to avoid severe or fatal incidents.
Fanikos, John; Fiumara, Karen; Baroletti, Steve; Luppi, Carol; Saniuk, Catherine; Mehta, Amar; Silverman, Jon; Goldhaber, Samuel Z
This study reviewed 863 alerts generated from the infusion of anticoagulants in 355 patients from October 2003 to January 2005. Alerts were generated by smart infusion technology pumps and recorded in the devices' memory. The most common alerts were underdose alerts (59.8%), followed by overdose alerts (31.3%) and duplicate drug therapy alerts (8.9%). In response to the alerts, users' most frequent action was to cancel (46.5%) or reprogram (43.1%) the infusions. The highest percentage of alerts occurred from 2 to 4 p.m. During the study, there were 4 infusion rate errors, compared with 15 in the immediately preceding 16-month period. In conclusion, smart infusion technology intercepted keypad entry errors, thereby reducing the likelihood of intravenous anticoagulant overdose or underdose. Dose or infusion rate programming during intravenous anticoagulation is an important targets for medication safety interventions.
Fernández Sarmiento, Jaime; Varela, María A; Pinzón, Carlos E
The current practice of plasmapheresis at most centers employs anticoagulation of the extracorporeal circuit, which has been associated with complications. There are few studies evaluating the efficacy and safety of using plasmapheresis without any anticoagulation. We report our experience using this strategy in children (1 month to 18 years old) over a period of 5 years. Two hundred forty-three plasmapheresis sessions without anticoagulation of the extracorporeal circuit, in 27 pediatric patients, were analyzed. Of these, 81.4% were female and the predominant age range was 12-18 years (70.3%). One hundred percent of the patients had PRISM III scale low mortality risk, and the main indication of therapy was acute rejection after renal transplantation (25.9%), followed by recurrence of focal segmental sclerosis in the transplanted kidney (17.2%). Filtration lasted more than 3 hours in 86.8% of cases, with bleeding complications in 2.9% of patients requiring early termination due to associated complications in 3.2% of cases. Other complications were paresthesias (0.41%), vomiting (5%), hypertension during (67.4%) and after therapy (64.6%), and hyperchloremia (46.5%). In our experience, plasmapheresis without circuit anticoagulation in children is safe and effective, with a low frequency of bleeding and hydroelectrolytic complications, allowing the achievement of therapeutic goals without altering therapy duration and efficiency. Prospective studies are needed to corroborate these findings. Copyright © 2016 Elsevier Ltd. All rights reserved.
The dynamic evolution of therapeutic options including the use of vitamin K antagonists (VKA), non-vitamin K oral anticoagulants (NOAC), more potent antiplatelet drugs as well as new generation drug-eluting stents could lead to the view that the current recommendations on the management of patients with percutaneous coronary intervention (PCI) requiring oral anticoagulation do not keep up with the results of several clinical studies published within the last 5 years. In the present overview, we summarize the recent advances in antithrombotic management used in atrial fibrillation patients undergoing PCI for stable coronary artery disease or acute coronary syndrome (ACS). The safety and efficacy of prasugrel and ticagrelor taken with oral anticoagulants also remain to be established in randomized trials; therefore the P2Y12 inhibitor clopidogrel on top of aspirin or without is now recommended to be used together with a VKA or NOAC. It is still unclear which dose of a NOAC in combination with antiplatelet agents and different stents should be used in this clinical setting and whether indeed NOAC are safer compared with VKA in such cardiovascular patients. Moreover, we discuss the use of anticoagulation in addition to antiplatelet therapy for secondary prevention in patients with ACS. To minimize bleeding risk in anticoagulated patients following PCI or ACS, the right agent should be prescribed to the right patient at the right dose and supported by regular clinical evaluation and laboratory testing, especially assessment of renal function when a NOAC is used. PMID:27980542
Poli, Daniela; Antonucci, Emilia; Dentali, Francesco; Erba, Nicoletta; Testa, Sophie; Tiraferri, Eros; Palareti, Gualtiero
To evaluate the risk of recurrent intracranial hemorrhage (ICH) in patients on vitamin K antagonists (VKAs) after a first episode of ICH. The Cerebral Haemorrhage in patients Restarting Oral Anticoagulant Therapy (CHIRONE) Study collected data of patients eligible for the study from the database of 27 centers affiliated with the Italian Federation of Anticoagulation Clinics. We enrolled 267 patients (163 male, median age 73.9 years) who had received VKA anticoagulation after an ICH event. During the total period of follow-up (778 patient-years), ICH recurred in 20 patients (7.5%; rate 2.56 × 100 patient-years) at a median time of 16.5 months, and was fatal in 5 patients (25%; rate 0.4 × 100 patient-years). Male sex, hypertension, prosthetic valves, previous ischemic stroke, renal failure, cancer, and spontaneous events were associated with the risk of recurrence, though none of them in isolation reached statistical significance. More than one-third of spontaneous recurrences occurred in patients with a posttraumatic index event. Our results show that patients with a history of ICH carry a significant risk of recurrent ICH when treated with VKA anticoagulation. The risk is also present, though to a lower degree, in patients with previous posttraumatic events. All patients with a history of ICH require a careful evaluation of their thromboembolic risk to estimate the net clinical benefit of (re)starting anticoagulation with VKAs.
Hellfritzsch, Maja; Husted, Steen Elkjaer; Grove, Erik Lerkevang; Rasmussen, Lotte; Poulsen, Birgitte Klindt; Johnsen, Søren Paaske; Hallas, Jesper; Pottegård, Anton
Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on pattern of switching and discontinuation of oral anticoagulants. To address this, we conducted a nationwide drug utilization study including all registered Danish atrial fibrillation patients initiating a non-VKA oral anticoagulant (NOAC) between August 2011 and February 2016. We assessed changes in anticoagulant treatment, including switching between oral anticoagulants and discontinuation of NOACs, and explored patient characteristics predicting these changes. We identified 50,632 patients with atrial fibrillation initiating NOAC therapy within the study period. The majority initiated dabigatran (49.9%) and one-third had previously used VKA. Within 1 year, 10.1% switched to VKA, 4.8% switched to another NOAC and 14.4% discontinued treatment. The frequencies of switching to VKA and discontinuation were highest among NOAC users of young age (<55 years) and with low CHA2 DS2 -VASc score (=0). However, the majority of patients (87.3%) stopping NOAC treatment had a CHA2 DS2 -VASc score ≥1. We conclude that switching from VKA to NOAC, and to a lesser extent from NOAC to VKA, is common, as is early treatment discontinuation. The majority of treatment changes are observed in patients at increased risk of stroke. More research is warranted on the risks of bleeding and thromboembolism associated with switching and discontinuation of NOACs as well as the underlying reasons why these treatment changes occur.
Background After addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages. Results Responses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid). Conclusion High dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in
Hankey, Graeme J
This review article discusses the following, as yet unanswered, questions and research priorities to optimise patient management and stroke prevention in atrial fibrillation with the new direct oral anticoagulants (NOACs): 1. In patients prescribed a NOAC, can the anticoagulant effects or plasma concentrations of the NOACs be measured rapidly and reliably and, if so, can "cut-off points" between which anticoagulation is therapeutic (i.e. the "therapeutic range") be defined? 2. In patients who are taking a NOAC and bleeding (e.g. intracerebral haemorrhage), can the anticoagulant effects of the direct NOACs be reversed rapidly and, if so, can NOAC-associated bleeding and complications be minimised and patient outcome improved? 3. In patients taking a NOAC who experience an acute ischaemic stroke, to what degree of anticoagulation or plasma concentration of NOAC, if any, can thrombolysis be administered safely and effectively? 4. In patients with a recent cardioembolic ischaemic stroke, what is the optimal time to start (or re-start) anticoagulation with a NOAC (or warfarin)? 5. In anticoagulated patients who experience an intracranial haemorrhage, can anticoagulation with a NOAC be re-started safely and effectively, and if so when? 6. Are the NOACs effective and safe in multimorbid geriatric people (who commonly have atrial fibrillation and are at high risk of stroke but also bleeding)? 7. Can dose-adjusted NOAC therapy augment the established safety and efficacy of fixed-dose unmonitored NOAC therapy? 8. Is there a dose or dosing regimen for each NOAC that is as effective and safe as adjusted-dose warfarin for patients with atrial fibrillation who have mechanical prosthetic heart valves? 9. What is the long-term safety of the NOACs?
Hauguel, M; Boelle, Py; Pichereau, C; Bourcier, S; Bigé, N; Baudel, JL; Maury, E; Guidet, B; Ait-Oufella, H
Abstract Bleeding is the most frequent complication of anticoagulant therapy, responsible for a number of hospitalizations or deaths. However, studies describing the management and prognosis factors of extra-cerebral anticoagulant-related bleedings in intensive care unit (ICU) are lacking. Retrospective observational study in an 18-bed ICU in a tertiary teaching hospital. From January 2000 to December 2013, all consecutive patients, older than 18 years, admitted for severe anticoagulant-related bleeding (SAB) except intracerebral site were included. A total of 100 patients were included, the mean age was 77 ± 11 years and 62% were women. SAB incidence in ICU doubled over 10 years (P = 0.03). In ICU, the average length of stay was 5 ± 6 days and mortality was 30%. Nonsurviving patients had a higher SAPS II (78 ± 24 vs 53 ± 24, P < 0.0001), a higher SOFA (9.0 ± 3.6 vs 4.7 ± 3.4, P < 0.0001) and received more frequently support therapy such as mechanical ventilation (87% vs 16%, P < 0.0001) and vasopressors (90% vs 27%, P < 0.0001). The volume of blood-derived products transfused was more important in nonsurvivors mainly during the first 24 hours of resuscitation. Rapid anticoagulant reversal therapy was associated with better prognosis (ICU survivors 66% vs 39%, Fisher test P = 0.04). Anterior abdominal wall was identified as a frequent site of bleeding (22%) due to epigastric artery injury during subcutaneous injection of heparin and was associated with a large mortality (55%). Extra-cerebral SAB is a life-threatening complication that requires rapid resuscitation and anticoagulant reversal therapy. Injection of heparin should be done carefully in the subcutaneous tissue thereby avoiding artery injury. PMID:26632750
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
Heneghan, Carl J; Garcia-Alamino, Josep M; Spencer, Elizabeth A; Ward, Alison M; Perera, Rafael; Bankhead, Clare; Alonso-Coello, Pablo; Fitzmaurice, David; Mahtani, Kamal R; Onakpoya, Igho J
The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0
Ratzinger, Franz; Lang, Mona; Belik, Sabine; Jilma-Stohlawetz, Petra; Schmetterer, Klaus G; Haslacher, Helmuth; Perkmann, Thomas; Quehenberger, Peter
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 di