ROTEM Testing for Direct Oral Anticoagulants

AbstractDirect oral anticoagulants (DOACs) are increasingly used worldwide for the prevention of stroke in patients with atrial fibrillation and to prevent or treat venous thromboembolism. In situations such as serious bleeding, the need for urgent surgery/intervention or the management of a thromboembolic event, the laboratory measurement of DOACs levels or anticoagulant activity may be required. Rotational thromboelastometry (ROTEM) is a viscoelastic hemostatic assay (VHA) which has been used in emergencies (trauma and obstetrics), and surgical procedures (cardiac surgery and liver transplants), but experience with this assay in DOACs-treated patients is still limited. This article reviews the use of ROTEM in the setting of DOACs therapy, focusing on DOACs-associated bleeding and the use of this VHA for the management of reversal strategies for DOACs-associated anticoagulation.

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FEIBA™ for Patients on Direct Oral Anticoagulants Requiring Urgent Surgery

Blood ◽

10.1182/blood.v124.21.4259.4259 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4259-4259

Author(s):

Joseph Shaw ◽

Gregoire Le Gal ◽

Melanie Tokessy ◽

Nancy Cober ◽

Elianna Saidenberg ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Vitamin K ◽

Major Bleeding ◽

Femur Fracture ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Ischemic Bowel ◽

Urgent Surgery ◽

Thrombotic Complications

Abstract Introduction: A recent Canadian population based review showed a rapid increase in use of direct oral anticoagulants (DOACs) for prevention of systemic embolism in patients with atrial fibrillation (AF) (Xu et al.). These drugs offer advantages over traditional vitamin K antagonists (VKA) including fixed dosing regimens and elimination of laboratory monitoring. In Canada, patients receiving VKA requiring urgent surgery are reversed with prothrombin complex concentrates (PCC) with or without vitamin K. DOAC specific antidotes are under development and use of PCCs or activated PCC for the purposes of DOAC reversal for emergent procedures is controversial. We describe the use of activated PCC (FEIBA™) in patients receiving the DOACs (dabigatran, apixaban, or rivaroxaban) who required urgent surgical intervention. Methods: A retrospective review of patients receiving DOACs and requiring urgent reversal of anticoagulation effect for procedures or surgery at The Ottawa Hospital between January 2013 and June 2014 are included. Major bleeding was defined using the ISTH criteria (Schulman et al.). The primary outcome was major bleeding peri-operatively and secondary outcome was adverse embolic and thrombotic events during follow up. Results: Five patients were identified: two patients were on rivaroxaban, two were on apixaban, and one was on dabigatran. Baseline characteristics are shown in Table 1. One patient was on rivaroxaban for secondary prevention of venous thromboembolism (VTE), while the remaining patients had AF. Three patients required laparotomy for bowel obstruction; one patient required open femur fracture repair; and one patient required angiography and stent placement for ischemic bowel. A large majority of patients (80%) had received a dose of anticoagulant on the day of surgery. One patient required intra-operative blood transfusion. There were no embolic or thrombotic complications following FEIBA™ administration and all patients’ survived hospitalization. Conclusions: The use of FEIBA™ for reversal of DOAC effect for urgent surgery in this cohort of patients was effective and not associated with adverse thrombotic complications. Prospective studies evaluating use of potential benefits and harms of FEIBA™ for reversal of DOACs in patients requiring emergent surgery are needed. Abstract 4259. Table 1: Patients on DOACs Requiring Urgent Procedure Patient (Age and Gender) Indication For DOAC [AF(CHADS2); VTE] DOAC and Dosage Surgery/ Procedure Units of PRBCs Transfused FEIBA™ Dose (IU) Adverse Events post-FEIBA™ administration Survived Hospitalization 91 Female AF (4) Rivaroxaban 15 mg daily Femur fracture ORIF 3, intra-operatively 1812 -- Yes 50 Male VTE Apixaban 5 mg BID Laparotomy for SBO 0 1350 -- Yes 50 Female AF (4) Apixaban 2.5 mg BID Angiography + SMA stent for ischemic bowel 0 3918 -- Yes 77 Male AF (2) Rivaroxaban 20 md daily Laparotomy for incarcerated hernia/SBO 0 3241 Venous oozing intra-operatively Yes 78 Male AF (3) Dabigatran 110 mg BID SBO/ Femoral hernia repair 0 6000 -- Yes AF = atrial fibrillation; BID = twice daily; CHADS = congestive heart failure, hypertension, age, diabetes, stroke; DOAC = direct oral anticoagulant; IU = international units; ORIF = open reduction internal fixation; PRBC = packed red blood cells; SBO = small bowel obstruction; SMA = superior mesenteric artery; VTE = venous thromboembolism References: Schulman, S et al. J Thromb Haemost 2010; 8: 202–4. Xu, Y et al. CMAJ Open 2013; 1:E115-E119. Disclosures Off Label Use: FEIBA is an activated prothrombin complex concentrate that was used during management of patients on direct oral anticoagulants requiring urgent surgery..

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Faculty Opinions recommendation of Efficacy and Harms of Direct Oral Anticoagulants in the Elderly for Stroke Prevention in Atrial Fibrillation and Secondary Prevention of Venous Thromboembolism: Systematic Review and Meta-Analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725514028.793512947 ◽

2016 ◽

Author(s):

Nanette Wenger

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Venous Thromboembolism ◽

Secondary Prevention ◽

Stroke Prevention ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

The Elderly

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Abstract 17301: Safety of Direct Oral Anticoagulants Compared to Warfarin for Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.17301 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Ali Hage ◽

Daniel Dolan ◽

Viviane G Nasr ◽

Luis Castelo-Branco ◽

Daniel Motta-Calderon ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Cardiac Surgery ◽

Hospital Readmission ◽

Lower Risk ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Secondary Outcome ◽

Systemic Embolization

Introduction: The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation (POAF) is limited and mostly founded on clinical trials that excluded this patient population. Hypothesis: We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with POAF. Methods: We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality, with secondary outcome of hospital readmission. We performed a random-effects meta-analysis. Results: We found 3 clinical trials, 1 prospective and 12 retrospective cohort studies eligible for inclusion with a total of 10,538 patients (3,207 DOAC patients and 7,331 warfarin patients). The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50 to 0.81, I2: 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41 to 1.01, I2: 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74 to 1.10, I2: 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74 to 1.37, I2: 26.5%) The secondary outcome of hospital readmission had similar risk between groups. Conclusions: Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding or mortality.

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The Combination of Oral Anticoagulant and Antiplatelet Therapies: Stay One Step Ahead

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420923528 ◽

2020 ◽

Vol 25 (5) ◽

pp. 391-398

Author(s):

Fabiana Lucà ◽

Simona Giubilato ◽

Stefania Angela Di Fusco ◽

Angelo Leone ◽

Stefano Poli ◽

...

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Antiplatelet Therapy ◽

Oral Anticoagulant ◽

Acute Coronary Syndromes ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Clinical Scenarios ◽

Coronary Syndromes

Antithrombotic drugs, which include antiplatelets and anticoagulants, are effective in prevention and treatment of many cardiovascular disorders such as acute coronary syndromes, stroke, and venous thromboembolism and are among the drugs most commonly prescribed worldwide. The advent of direct oral anticoagulants, which are safer alternatives to vitamin K antagonists and do not require laboratory monitoring, has revolutionized the treatment of nonvalvular atrial fibrillation and venous thromboembolism. The combination of oral anticoagulant and antiplatelet therapy is required in many conditions of great clinical impact such as the coexistence of atrial fibrillation and coronary artery disease, with indication to percutaneous coronary intervention. However, strategies that combine anticoagulant and antiplatelet therapies lead to a significant increase in bleeding rates and it is crucial to find the right combination in the single patient in order to optimize the ischemic and bleeding risk. The aim of this review is to explore the evidence and controversies regarding the optimal combination of anticoagulant and antiplatelet therapy through the consideration of past dogmas and new perspectives from recent clinical trials and to propose a tailored therapeutic approach, according to specific clinical scenarios and individual patient characteristics. In particular, we separately explored the clinical settings of stable and acute coronary syndromes and percutaneous revascularization in patients with atrial fibrillation.

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Reasons for Switching from Warfarin to a Direct Oral Anticoagulant: A Retrospective Study

Blood ◽

10.1182/blood-2018-99-116974 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5060-5060

Author(s):

Siavash Piran ◽

Marlene Robinson ◽

Erjona Kruja ◽

Sam Schulman

Keyword(s):

Atrial Fibrillation ◽

Cardiac Surgery ◽

Drug Interactions ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Retrospective Chart Review ◽

Mechanical Valve ◽

Adherence Rate ◽

Valve Prosthesis ◽

Significant Difference

Abstract Background: Direct oral anticoagulants (DOACs) are slowly replacing warfarin for the prevention of stroke in atrial fibrillation and treatment and secondary prevention of venous thromboembolism. Patients with poor time in therapeutic range (TTR) are often switched to a DOAC. Poor TTR can be due to drug interactions but if the reason is poor compliance, outcomes could be worse using a DOAC without monitoring. Methods: To understand the compliance patterns we performed a retrospective chart review in patients from the anticoagulation clinic at Hamilton General Hospital that were switched from warfarin to a DOAC from April 2013 to April 2018. Patients who were taking warfarin for ≥ 2 months for any indication, except for mechanical valve prosthesis, and who were switched to a DOAC were included. We excluded patients who had a DOAC-to-DOAC switch, patients who had no reported TTR available, and those who were temporarily on warfarin after cardiac surgery. The documented reasons for a switch from warfarin to a DOAC were compared between patients with TTR ≤ 60% and >60%. Non-adherence to international normalized ratio (INR) monitoring was considered if >20% of tests were not done or delayed for more than 2 days. Results: A total of 643 eligible patients were initially screened and 288 patients were excluded: 179 had no available TTR, 93 were temporarily on warfarin after cardiac surgery, 11 were not actually switched from warfarin to a DOAC, and 5 had a DOAC-to-DOAC switch. The remaining 355 patients were included in the analysis: 223 had a TTR ≤ 60% and 132 patients had a TTR >60%. There were no differences in the median age or gender distribution. The most common indication for anticoagulation was atrial fibrillation in both groups. The median TTR was 43% in the TTR ≤ 60% group and 71% in the TTR >60% group. The median duration on anticoagulation with warfarin was significantly longer for the TTR >60% group compared with the TTR ≤ 60% group (42 months versus 19 months; P <0.001). Apixaban was the most common DOAC of choice for the switch in both groups. The most common documented reasons for a switch in the group with a TTR >60% were: switch by another physician for unknown reason (n=36), bleeding (n=30), and patient preference (n=20). The most common reasons for a switch in those with a TTR ≤ 60% were: unstable INR readings (n=42), drug interactions (n=33), and bleeding (n=30). There was no significant difference in the rate of non-adherence with the scheduled INR monitoring (42% in the group with a TTR >60% versus 49% in those with a TTR ≤ 60%). Conclusion: We found that about half of the patients on chronic anticoagulation with warfarin and switched to a DOAC were non-adherent with the scheduled INR monitoring. This, in combination with low TTR, should alert the physician of possible non-compliance with taking DOACs. Further prospective studies are needed to examine the DOAC adherence rate and clinical outcomes in this specific population. Disclosures Schulman: Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; Sanofi: Honoraria; Bayer: Honoraria.

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