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Background: Cancer-associated venous thromboembolism (VTE) management guideline recommendations include continued therapeutic anticoagulation while active cancer persists. The Federal Drug Administration label for apixaban for secondary VTE prevention includes a dose reduction to 2.5 mg twice daily after 6 months of treatment., Objectives: The study's purpose was to determine whether this dose reduction is advisable for cancer-associated VTE., Methods: A randomized, double-blind trial compared apixaban 2.5 mg with 5 mg twice daily for 12 months among cancer patients with VTE who had completed 6 to 12 months of anticoagulation therapy. The primary outcome was combined major bleeding plus clinically relevant nonmajor bleeding., Results: Of 370 patients recruited, 360 were included in the intention-to-treat analyses. Major plus clinically relevant nonmajor bleeding occurred in 16 of 179 patients (8.9%) in the apixaban 2.5 mg group compared with 22 of 181 patients (12.2%) in the 5 mg group (hazard ratio [HR], 0.72; 95% CI, 0.38-1.37; P = .39). Major bleeding occurred in 2.8% of the apixaban 2.5 mg group and in 2.2% of the 5 mg group (HR, 1.26; 95% CI, 0.34-4.66; P = .73). Recurrent VTE or arterial thrombosis occurred in 9 of 179 patients (5.0%) in the apixaban 2.5 mg group and 9 of 181 patients (5.0%) in the 5 mg group (HR, 1.0; 95% CI, 0.40-2.53; P = 1.00). All-cause mortality rates were similar between groups, 13% vs 12% (HR, 1.14; 95% CI, 0.63-2.04; P = .67)., Conclusion: For secondary prevention of cancer-associated VTE, apixaban 2.5 mg compared with 5 mg twice daily did not lower combined bleeding events (EVE trial NCT03080883)., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

History of venous thromboembolism (VTE) is prevalent among patients undergoing hematopoietic cell transplantation (HCT). Management of anticoagulation is particularly challenging as most patients will have chemotherapy-induced thrombocytopenia while awaiting engraftment post-HCT. We conducted a retrospective study of autologous and allogeneic HCT recipients with prior VTE from 2006-2015 to 1) compare anticoagulant strategies on short-term VTE recurrence and bleeding and 2) assess predictors for VTE recurrence beyond 30 days. Patients with VTE were allocated to two cohorts based on anticoagulant strategy at thrombocytopenia onset and underwent inverse probability weighting to assess primary outcomes of VTE recurrence and bleeding within 30 days post-HCT. Subsequently, multivariable logistic regression model was used to assess the association of 100-day VTE recurrence by the HIGH-2-LOW VTE risk assessment score and whether patients resumed anticoagulation at platelet recovery. Thirteen percent of recipients had VTE prior to HCT; of those meeting inclusion criteria, 227 continued anticoagulation and 113 temporarily discontinued it. Anticoagulant strategy was not significantly associated with decreased risk of VTE recurrence within 30 days (3% vs 4%, p = 0.61); however, risk of overall bleeding was non-significantly higher in those who continued vs discontinued anticoagulation (41% vs 31%, p = 0.08). In a subgroup of 250 allogeneic HCT patients, every one-point increase of HIGH-2-LOW score was significantly associated with VTE recurrence at 100 days (OR 1.57 [95% CI 1.10-2.23]), while anticoagulation resumption upon platelet engraftment was associated with lower recurrent risk (OR 0.48 [0.20-1.14]). Temporarily withholding anticoagulation during thrombocytopenia may optimize risk-benefit tradeoffs, though additional strategies are essential to prevent VTE recurrence after hematopoietic recovery., (© 2021 Wiley Periodicals LLC.)

In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting., Competing Interests: N. Kraaijpoel has nothing to disclose. M. Di Nisio reports personal fees from Daiichi Sankyo. F.I. Mulder has nothing to disclose. N. van Es reports personal fees from Daiichi Sankyo and Pfizer. J. Beyer-Westendorf reports grants and personal fees from Bayer AG, Boehringer-Ingelheim, Daiichi Sankyo, Pfizer and Portola. M. Carrier reports grants from BMS and Leo Pharma, and personal fees from Pfizer, Bayer, Sanofi and Leo Pharma. D. Garcia reports grants and personal fees from Daiichi Sankyo, Janssen and Incyte, and personal fees from BMS and Boehringer-Ingelheim. M. Grosso, M.F. Mercuri, G. Zhang and L. Schwocho are employees of Daiichi Sankyo Inc. A.K. Kakkar reports grants and personal fees from Bayer AG, and personal fees from Boehringer-Ingelheim, Janssen Pharma, Sanofi SA and Verseon. S. Middeldorp reports grants and personal fees from GSK, BMS/Pfizer, Aspen and Daiichi Sankyo, and personal fees from Bayer, Boehringer-Ingelheim, and grants from Sanquin. C. Rojas Hernandez reports personal fees from Daiichi Sankyo. A. Santamaria reports personal fees from Bayer AG, Boehringer-Ingelheim, Pfizer, Bristol-Myers Squibb, Daiichi Sankyo, LeoPharma, Sanofi-Aventis, Rovia and SOBI. A. Segers reports grants from Daiichi Sankyo, IONIS Pharmaceuticals and Janssen Pharmaceuticals. P. Verhamme reports grants and personal fees from Bayer Healthcare, LeoPharma, Daiichi Sankyo and Boehringer-Ingelheim, and personal fees from BMS, Portola, Medscape, Medtronic and Pfizer. T.F. Wang has nothing to disclose. J.I. Weitz reports personal fees from Daiichi-Sankyo, Bayer Healthcare, BMS, Boehringer-Ingelheim, Ionis Pharmaceuticals, Janssen, Johnson and Johnson, Pfizer, Portola, Medscape and Novartis. J.I. Zwicker reports grants from Quercegen and Incyte, and personal fees from Daichii Sankyo and Parexel. H.R. Büller reports personal fees from Daiichi Sankyo, Bayer Healthcare, BMS/Pfizer, Boehringer-Ingelheim, Portola, Medscape, Eli Lilly, Sanofi Aventis and Ionis. G.E. Raskob reports personal fees from Daiichi Sankyo, Itreas, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Isis Pharmaceuticals, Janssen, Pfizer and Portola., (Georg Thieme Verlag KG Stuttgart · New York.)

The North American Thrombosis Forum Atrial Fibrillation Action Initiative consensus document is a comprehensive yet practical briefing document focusing on stroke and bleeding risk assessment in patients with atrial fibrillation, as well as recommendations regarding anticoagulation options and management. Despite the breadth of clinical trial data and guideline recommendation updates, many clinicians continue to struggle to synthesize the disparate information available. This problem slows the uptake and utilization of updated risk prediction tools and adoption of new oral anticoagulants. This document serves as a practical and educational reference for the entire medical community involved in the care of patients with atrial fibrillation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Whether and when to resume oral anticoagulant therapy for patients who survive warfarin-related intracranial hemorrhage (ICH) remains a dilemma lacking consensus recommendations and high-quality evidence to guide clinical decision making., Objective: To determine the incidences of recurrent ICH, thrombosis, and death in relation to resumption or non-resumption of warfarin therapy during the 365 days after incident ICH., Methods: We conducted a retrospective cohort study of adult patients in an integrated healthcare delivery system who were receiving warfarin therapy at the time of incident (index) ICH between 1/1/2000 and 12/31/2007 and survived to hospital discharge. The primary outcomes were recurrent ICH, thrombosis (stroke, systemic embolism, and venous thromboembolism), and all-cause mortality during the 365 days following index ICH. Patients were assigned to one of two groups defined by warfarin therapy resumption after the index ICH., Results: There were 160 patients discharged from the hospital following warfarin-related index ICH; of these 54 (33.8%) resumed warfarin therapy and 106 (66.2%) did not. Recurrent ICH occurred in a numerically greater, but statistically non-significant, proportion of patients who did not resume warfarin therapy (7.6% vs. 3.7%, p=0.497). Similarly, patients who did not resume warfarin had a three-fold higher (12.3% vs. 3.7%, p=0.092) and approximately two-fold higher (31.1% vs. 18.5%, p=0.089) rates of thrombosis and all-cause mortality, respectively, during follow up., Conclusion: Resumption of warfarin therapy following warfarin-associated ICH appeared not to be associated with increased risk of recurrent ICH but trended toward reduced thrombosis and all-cause mortality., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A 70-year-old male with a history of atrial fibrillation who is being anticoagulated with dabigatran etexilate presents to the emergency room with melena. He reports taking his most recent dose of dabigatran more than 2 hours ago. On examination, he is hypotensive and tachycardic, and he continues to have melanotic stools. Laboratory testing reveals a calculated creatinine clearance of 15 mL/min, a prothrombin time of 16.5 seconds (reference range: 11.8-15.2 seconds), an international normalized ratio of 1.2 (reference range: 0.9-1.2), and an activated partial thromboplastin time of 50 seconds (reference range: 22.2-33.0 seconds). You are asked by the emergency medicine physician whether hemodialysis should be considered to decrease the patient's plasma dabigatran level., (© 2014 by The American Society of Hematology. All rights reserved.)

Target-specific oral anticoagulants (TSOACs) that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are effective and safe alternatives to vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH). Although these agents have practical advantages compared with VKAs and LMWH, there are no antidotes that reverse their anticoagulant effect. Clinical evidence for the efficacy of nonspecific therapies that promote formation of fibrin (prothrombin complex concentrate [PCC], activated PCC [aPCC], and recombinant factor VIIa) in the setting of TSOAC-associated bleeding is lacking, and these prohemostatic products are associated with a risk of thrombosis. In the absence of specific antidotes, addition of PCC or aPCC to maximum supportive therapy may be reasonable for patients with severe or life-threatening TSOAC-associated bleeding. Targeted antidotes for these agents are in development.

Background: Patients with atrial fibrillation who are vitamin K antagonist (VKA)-naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced patients., Methods and Results: Using data from ARISTOTLE, we assessed baseline characteristics and the treatment effect of apixaban versus warfarin in the VKA-naive and VKA-experienced cohorts. We compared rates of study drug discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA naive, and 10,401 were VKA experienced. At baseline, both groups were similar with respect to age and congestive heart failure, hypertension, age, diabetes, stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs 33%). The effect of apixaban on the primary efficacy and safety outcomes was similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI 0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for interaction = 0.50). Permanent study drug discontinuation was numerically less likely in patients receiving apixaban whether they were VKA naive (HR for discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the mean/median times in therapeutic range were lower in the VKA-naive group (VKA-naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001)., Conclusion: The treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The rates of stroke/systemic embolism and major bleeding were numerically lower among the patients assigned to apixaban, irrespective of prior VKA use., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: We observed that centhaquin, a cardiovascular active agent, reduces blood lactate levels. Because blood lactate is an important indicator of end-organ perfusion, we determined the resuscitative effect of centhaquin in hemorrhaged rats., Materials and Methods: Male, adult Sprague-Dawley rats (Harlan, Indianapolis, IN) were anesthetized with urethane, and a pressure catheter SPR-320 was placed in the left femoral artery, and a pressure-volume catheter SPR-869 was placed into the left ventricle through carotid artery. Hemorrhage was induced by withdrawing blood from the right femoral artery, and mean arterial pressure was maintained between 35 and 40 mm Hg for 30 min after which resuscitation was performed using normal saline (control), 3% hypertonic saline, or centhaquin dissolved in 3% hypertonic saline. Arterial blood pH, pO(2), pCO(2), lactate, hematocrit, and cardiovascular parameters were measured before the induction of hemorrhage (baseline), 30 min after induction of hemorrhagic shock, and every 60 min thereafter until the animal expired., Results: Hypertonic saline was effective in reducing blood lactate levels and improving cardiac output (CO) of hemorrhaged rats. Centhaquin dissolved in hypertonic saline produced a significantly greater decrease in blood lactate and increase in mean arterial pressure and CO compared with hypertonic saline in hemorrhaged rats. Fraction survival at 250 min was 0 when resuscitated with hypertonic saline, whereas it was 0.8 with centhaquin., Conclusions: Centhaquin significantly improved the resuscitative effect of hypertonic saline by increasing CO, reducing blood lactate, and improving survival time of hemorrhaged rats., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Genotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all dosing method., Objective: The objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing the occurrence of serious bleeding events and over-anticoagulation., Data Sources: The authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a "standard" dose control algorithm in adult patients taking warfarin for the first time., Review Methods: Two reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included minor bleeding, thrombotic events and other measures of anticoagulation quality., Results: Three of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms, length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07) in the pharmocogenetic arm., Conclusions: We did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice.

Background: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain., Objective: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy., Design: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment., Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy., Patients: Nonbleeding patients with INR values of 4.5 to 10.0., Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed)., Measurements: Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes)., Results: 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001)., Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed., Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0., Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research.

Background: Significant uncertainty surrounds the treatment of patients who must discontinue warfarin sodium therapy before an invasive procedure. In part, the uncertainty results from the lack of published information about the risk of thromboembolism associated with short-term warfarin therapy interruption. We aimed to assess the frequency of thromboembolism and bleeding within a large cohort of patients whose warfarin therapy was temporarily withheld for an outpatient invasive procedure., Methods: This prospective, observational cohort study was performed at 101 sites (primarily community-based physician office practices) in the United States. Enrollment was conducted from April 4, 2000, to March 6, 2002. The main outcome measures were thromboembolism or clinically significant hemorrhage within 30 days of warfarin therapy interruption., Results: A total of 1293 episodes of warfarin therapy interruption in 1024 individuals were included. The mean (SD) patient age was 71.9 (10.6) years; 438 (42.8%) were female. The most common indications for anticoagulant therapy were atrial fibrillation (n=550), venous thromboembolism (n=144), and mechanical heart valve (n=132). The most common procedures were colonoscopy and oral and ophthalmic surgery. Perioperative heparin or low-molecular-weight heparin was used in only 8.3% of cases overall. Seven patients (0.7%; 95% confidence interval [CI], 0.3%-1.4%) experienced postprocedure thromboembolism within 30 days. None of the 7 patients who experienced thromboembolism received periprocedural bridging therapy. Six patients (0.6%; 95% CI, 0.2%-1.3%) experienced major bleeding, whereas an additional 17 patients (1.7%; 95% CI, 1.0%-2.6%) experienced a clinically significant, nonmajor bleeding episode. Of these 23 patients who had bleeding episodes, 14 received periprocedural heparin or low-molecular-weight heparin. The duration of warfarin therapy interruption was variable; however, more than 80% of patients had warfarin therapy withheld for 5 days or fewer., Conclusions: For many patients receiving long-term anticoagulation who need to undergo a minor outpatient intervention, a brief (< or =5 days) periprocedural interruption of warfarin therapy is associated with a low risk of thromboembolism. The risk of clinically significant bleeding, even among outpatients undergoing minor procedures, should be weighed against the thromboembolic risk of an individual patient before the administration of bridging anticoagulant therapy.

Objectives: Among warfarin-treated patients with international normalized ratio (INR) >5, we sought to determine the risk of major bleeding within 30 days., Background: For warfarin-treated patients, the risk of bleeding increases as the INR rises, particularly if the INR exceeds 4. The 30-day risk of hemorrhage among outpatients with excessively prolonged INR values is unknown., Methods: To assess anticoagulation care in the U.S., a cohort of 6,761 patients taking warfarin was prospectively assembled from 101 participating sites (43% were community-based cardiology practices). From this cohort, 1,104 patients were identified with a first episode of INR >5., Results: A total of 979 met eligibility criteria; complete follow-up information was available for 976 (99.7%). Ninety-six percent (n = 937) of patients had an INR value between 5 and 9; 80% of INR values were <7. Thirteen patients (1.3%) experienced major hemorrhage during the 30-day follow-up period; among patients whose INR was >5 and <9, 0.96% experienced major hemorrhage. None of the bleeding events was fatal. Intervention with vitamin K was uncommon (8.7%). Warfarin doses were withheld for the majority of patients. Fifty percent of patients who were managed conservatively and retested on day 4 or 5 had an INR of 2.0 or less., Conclusions: For warfarin-treated outpatients presenting with an INR >5 and <9, the 30-day risk of major bleeding is low (0.96%). Intervention with vitamin K among asymptomatic patients presenting with an INR <9 is not routine practice in the U.S.

Background: Despite published reports of its safety and efficacy, oral vitamin K (phytonadione) may not be widely used for patients with warfarin-associated coagulopathy. We tested the hypothesis that recommendations for phytonadione use from the American College of Chest Physicians (ACCP) Fifth Consensus Conference on Antithrombotic Therapy are not routinely incorporated into the clinical practice of many anticoagulation clinics., Methods: Surveys were mailed to 100 separate clinics in the southwestern region of the United States that are members of the Anticoagulation Forum, an association of anticoagulation clinic personnel and medical directors in the United States and Canada. Respondents were presented with 4 scenarios involving asymptomatic patients taking warfarin whose international normalized ratio is supratherapeutic. In each scenario, the respondents were told the patient's international normalized ratio and whether the patient was at "high" risk for bleeding., Results: Of 53 respondents, 13 (25%) indicated that their clinics never use oral phytonadione. Eighteen (34%) indicated that their clinics use subcutaneous phytonadione, despite the absence of a recommendation for this in the ACCP guidelines published in 1998. For each scenario, we made a judgment as to whether the respondent's management was consistent with guidelines found in the ACCP Fifth Consensus Conference on Antithrombotic Therapy. Overall, only 17 respondents (32%) provided all 4 answers consistent with the ACCP recommendations., Conclusion: For patients with supratherapeutic international normalized ratio values, our survey suggests that a substantial number of anticoagulation clinics underutilize oral phytonadione.

Background: Anticoagulation requires urgent reversal in cases of life-threatening bleeding or invasive procedures.Study Design and Methods: Network meta-analysis for comparing the safety and efficacy of warfarin reversal strategies including plasma and prothrombin complex concentrates (PCCs).Results: Seven studies including 594 subjects using reversal agents plasma, 3-factor-PCC (Uman Complex and Konyne), and 4-factor-PCC (Beriplex/KCentra, Octaplex, and Cofact) met inclusion criteria. Compared with plasma, patients receiving Cofact probably have a higher rate of international normalized ratio (INR) correction (risk difference [RD] 499 more per 1000 patients, 95% confidence interval [CI], 176-761, low certainty[LC]); higher reversal of bleeding (323 more per 1000 patients, 11-344 more, LC); and fewer transfusion requirements (0.96 fewer units, 1.65-0.27 fewer, LC). Patients receiving Beriplex/KCentra probably have a higher rate of INR correction (476 more per 1000 patients, 332-609 more, LC); higher reversal of bleeding (127 more per 1000 patients, 43 fewer to 236 more); and similar transfusion requirements (0.01 fewer units, 0.31 fewer to 0.28 more, high/moderate certainty). Patients receiving Octaplex probably have a higher rate of INR correction (RD 579 more per 1000 patients, 189-825 more, LC).Conclusions: PCCs probably provide an advantage in INR reversal compared to plasma. There was no added risk of adverse events with PCCs. [ABSTRACT FROM AUTHOR]

Background Scalp arteriovenous fistulas (AVFs) are a rare vascular disease usually presenting as a progressively increasing pulsating mass in the scalp. These lesions can be associated with mild to severe complications, including congestive heart failure. If ruptures, this pathology constitutes a life-threatening medical emergency because of its potential to cause severe bleeding and acute anemia. Methods We describe the case of a young woman with a ruptured Yokouchi type C scalp AVF with eyelid involvement. Results The patient presented with hypovolemic shock and acute anemia due to severe bleeding from the lesion. Emergent treatment through a combined endovascular and open surgical approach was required to stop bleeding and stabilize the patient. Conclusions Emergent and effective treatment is required to stop bleeding when a scalp AVF ruptures. A combination of endovascular embolization and microsurgical excision of the shunt is a treatment option. [ABSTRACT FROM AUTHOR]

Oncology patients are at a high risk of experiencing venous thromboembolism. Historically, venous thromboembolisms in cancer patients have been managed with low-molecular-weight heparin on the basis of the CLOT trial published in 2003. However, recent prospective data provide evidence for safe and effective direct oral anticoagulant use in this population. The purpose of this review article is to evaluate the current body of literature surrounding direct oral anticoagulant use in the oncology population and to highlight key practical considerations when prescribing these agents for patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Genotype-guided initial warfarin dosing may reduce over-anticoagulation and serious bleeding compared to a one-dose-fits-all dosing method.Objective: The objective of this review was to investigate the safety and efficacy of genotype-guided dosing of warfarin in reducing the occurrence of serious bleeding events and over-anticoagulation.Data Sources: The authors searched PubMed, EMBASE and International Pharmaceutical Abstracts through January 23, 2009, without language restrictions. Selected articles were randomized trials comparing pharmacogenetic dosing of warfarin versus a "standard" dose control algorithm in adult patients taking warfarin for the first time.Review Methods: Two reviewers independently extracted data and assessed study quality using a validated instrument. The primary outcomes were major bleeding and time spent within the therapeutic range International Normalized Ratio (INR). Secondary outcomes included minor bleeding, thrombotic events and other measures of anticoagulation quality.Results: Three of 2,014 studies (423 patients) met the inclusion and exclusion criteria. Differences in study quality, dosing algorithms, length of follow-up and outcome measures limited meta-analysis. Summary estimates revealed no statistically significant difference in bleeding rates or time within the therapeutic range INR. The highest quality study found no significant difference in primary or secondary outcomes, although there was a trend towards more rapid achievement of a stable dose (14.1 vs. 19.6 days, p = 0.07) in the pharmocogenetic arm.Conclusions: We did not find sufficient evidence to support the use of pharmacogenetics to guide warfarin therapy. Additional clinical trials are needed to define the optimal approach to use warfarin pharmacogenetics in clinical practice. [ABSTRACT FROM AUTHOR]

Study Objective. To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin. Design. Retrospective, matched cohort analysis. Setting. Centralized anticoagulation service in an integrated health care delivery system. Patients. A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age. Measurements and Main Results. Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05). Conclusion. Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation. [ABSTRACT FROM AUTHOR]

Source Citation: Lopes RD, de Barros E Silva PG, Furtado RH, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021;397:2253-63. 34097856. [ABSTRACT FROM AUTHOR]

The author comments on a study which investigates whether the contemporary bleeding risk model can predict major bleeding in patients with atrial fibrillation (AT) who are receiving warfarin therapy. It is asserted that the model accurately predicts the patient's risk of major bleeding, enabling the weighing of the risk and benefits of warfarin therapy. It is claimed that the proposed model has disadvantages including the complexity of the equation.

Keywords: anticoagulants; apixaban; atrial fibrillation; embolism, paradoxical; hemorrhage; stroke EN anticoagulants apixaban atrial fibrillation embolism, paradoxical hemorrhage stroke 958 960 3 09/19/22 20220920 NES 220920 Factor Xa inhibitors are the predominant type of oral anticoagulant for stroke prevention in atrial fibrillation.[1] Although recommendations exist on holding these medications before procedures with a low, intermediate, or high bleeding risk, whether and for how long to interrupt these medications around the time of a procedure continue to be debated.[2] In a previous analysis of the ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation), the 30-day postprocedure risk of stroke and major bleeding was similarly low in apixaban- and warfarin-treated patients, regardless of whether or not anticoagulation was interrupted at the time of a procedure.[3] Despite these results, many clinicians remain concerned about the risk of stroke when anticoagulation is held and the risk of bleeding when anticoagulation is not held before an invasive procedure. Atrial fibrillation, hemorrhage, stroke, anticoagulants, apixaban, embolism, paradoxical The rates of stroke/systemic embolism, myocardial infarction, death and major bleeding were <0.5% for patients on study drug 1 or 2 days after the procedure. [Extracted from the article]

Background: Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear.Methods: In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.Results: Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6).Conclusions: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .). [ABSTRACT FROM AUTHOR]

Background Amiodarone is an effective medication in preventing atrial fibrillation (AF), but it interferes with the metabolism of warfarin. Objectives This study sought to examine the association of major thrombotic clinical events and bleeding with the use of amiodarone in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods Baseline characteristics of patients who received amiodarone at randomization were compared with those who did not receive amiodarone. The interaction between randomized treatment and amiodarone was tested using a Cox model, with main effects for randomized treatment and amiodarone and their interaction. Matching on the basis of a propensity score was used to compare patients who received and who did not receive amiodarone at the time of randomization. Results In ARISTOTLE, 2,051 (11.4%) patients received amiodarone at randomization. Patients on warfarin and amiodarone had time in the therapeutic range that was lower than patients not on amiodarone (56.5% vs. 63.0%; p < 0.0001). More amiodarone-treated patients had a stroke or a systemic embolism (1.58%/year vs. 1.19%/year; adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.03 to 2.10; p = 0.0322). Overall mortality and major bleeding rates were elevated, but were not significantly different in amiodarone-treated patients and patients not on amiodarone. When comparing apixaban with warfarin, patients who received amiodarone had a stroke or a systemic embolism rate of 1.24%/year versus 1.85%/year (HR: 0.68, 95% CI: 0.40 to 1.15), death of 4.15%/year versus 5.65%/year (HR: 0.74, 95% CI: 0.55 to 0.98), and major bleeding of 1.86%/year versus 3.06%/year (HR: 0.61, 95% CI: 0.39 to 0.96). In patients who did not receive amiodarone, the stroke or systemic embolism rate was 1.29%/year versus 1.57%/year (HR: 0.82, 95% CI: 0.68 to 1.00), death was 3.43%/year versus 3.68%/year (HR: 0.93, 95% CI: 0.83 to 1.05), and major bleeding was 2.18%/year versus 3.03%/year (HR: 0.72, 95% CI: 0.62 to 0.84). The interaction p values for amiodarone use by apixaban treatment effects were not significant. Conclusions Amiodarone use was associated with significantly increased stroke and systemic embolism risk and a lower time in the therapeutic range when used with warfarin. Apixaban consistently reduced the rate of stroke and systemic embolism, death, and major bleeding compared with warfarin in amiodarone-treated patients and patients who were not on amiodarone. [ABSTRACT FROM AUTHOR]