Management of bleeding associated with dabigatran and rivaroxaban: a survey of current practices

University of Minnesota M.S. thesis. Major: Clinical Research. May 2013. Advisor: Mark T. Reding. 1 computer file (PDF); vi, 36 pages.Dabigatran and rivaroxaban are two new oral anticoagulants that have been recently approved as alternatives to warfarin. Clinical trials have shown non-inferiority of the new oral anticoagulants to warfarin for anti-thrombotic effects with equal to decreased bleeding risk. Unfortunately no standard method to assess the level of anticoagulation or reverse the effects of dabigatran or rivaroxaban is available. Current recommended management of bleeding patients taking dabigatran or rivaroxaban is based on expert opinion. To gain information from experience of physicians who have managed hemorrhaging patients, U.S. non-malignant hematologists were surveyed with a 31% response rate. In total, 43 cases of dabigatran associated hemorrhage and 5 cases of rivaroxaban associated bleeding were reported. Factor concentrates were used in 9 cases of dabigatran hemorrhage with perceived effectiveness ranging from 50-80%. A national registry is needed to track management of hemorrhages until antidotes become available

Management of the Bleeding Patient Receiving New Oral Anticoagulants: A Role for Prothrombin Complex Concentrates

Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage

Physician perceptions and use of reduced-dose direct oral anticoagulants for extended phase venous thromboembolism treatment

Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction. Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment. Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups. Results: Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose-reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces \u3c50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce. Conclusions: Most clinicians elect to dose-reduce DOACs for extended-phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high-risk periods

Physician perceptions and use of reduced‐dose direct oral anticoagulants for extended phase venous thromboembolism treatment

Abstract Background The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended‐phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision‐making regarding dose reduction. Aims Report clinician practice and characteristics surrounding dose reduction of DOACs for extended‐phase VTE treatment. Methods We conducted a 16‐question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k‐means clustering to identify distinct groups of dose‐reduction decision‐making. Random forest analysis explored demographics with respect to identified groups. Results Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose‐reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces <50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce. Conclusions Most clinicians elect to dose‐reduce DOACs for extended‐phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high‐risk periods

Executive Summary: Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously. Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update. Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations.</p

Selection Criteria for Internal Medicine Residency Applicants and Professionalism Ratings During Internship

OBJECTIVE: To determine whether standardized admissions data in residents' Electronic Residency Application Service (ERAS) submissions were associated with multisource assessments of professionalism during internship