A Historical Perspective on the Reversal of Anticoagulants.

There has been a landmark shift in the last several decades in the management and prevention of thromboembolic events. From the discovery of parenteral and oral agents requiring frequent monitoring as early as 1914, to the development of direct oral anticoagulants (DOACs) that do not require monitoring or dose adjustment in the late 20th century, great advances have been achieved. Despite the advent of these newer agents, bleeding continues to be a key complication, affecting 2 to 4% of DOAC-treated patients per year. Bleeding is associated with substantial morbidity and mortality. Although specific reversal agents for DOACs have lagged the release of these agents, idarucizumab and andexanet alfa are now available as antagonists. However, the efficacy of these reversal agents is uncertain, and complications, including thrombosis, have not been adequately explored. As such, guidelines continue to advise the use of nonspecific prohemostatic agents for patients requiring reversal of the anticoagulant effect of these drugs. As the indications for DOACs and the overall prevalence of their use expand, there is an unmet need for further studies to determine the efficacy of specific compared with nonspecific pro-hemostatic reversal agents. In this review, we will discuss the evidence behind specific and nonspecific reversal agents for both parenteral and oral anticoagulants.
Competing Interests: In the last 24 months, Dr. Crowther has sat on Advisory Boards for Syneos Health and Astra-Zeneca. He has prepared materials for, or presented on behalf of, Bayer, Pfizer, and CSL Behring. He has provided consulting services and presented on behalf numerous for profit, and not for profit, agencies, and provides consulting expertise for medical malpractice cases. He holds the Leo Pharma Chair in Thromboembolism Research with funding endowed at McMaster University.
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