Reversal of Direct Oral Anticoagulants

An Anticoagulation Forum guideline provides recommendations on the use of DOAC reversal agents.

Sponsoring Organization: The Anticoagulation Forum

Background

Direct oral anticoagulants (DOACs) have advantages over warfarin, including the lack of need for monitoring, a lower rate of major bleeding, absence of dietary vitamin K interaction, a shorter half-life, and lack of need for bridging with other agents around the time of procedures. Previously, some physicians and patients were reluctant to use DOACs because of the unavailability of an antidote. However, idarucizumab has recently been approved as a reversal agent for the DOAC dabigatran, and andexanet alfa has been approved as a reversal agent for the DOACs rivaroxaban and apixaban. Now, members of the Anticoagulation Forum have provided indications for proper use of these reversing agents.

Key Points

  • Reversing agents should be used in the context of life-threatening bleeding; major bleeding, if supportive measures (e.g. drug discontinuation, direct compression at the bleeding site, volume resuscitation, or transfusion) fail; and if a clinically relevant plasma DOAC level is demonstrated or suspected.
  • Reversing agents can be used prior to an invasive procedure if the procedure cannot be delayed, if the procedure is unsafe to perform while the patient is anticoagulated, and if a clinically relevant DOAC level is demonstrated or suspected.
  • Reversing agents are not indicated in patients with DOAC overdose without bleeding or in those presenting with trauma without bleeding.
  • If specific reversing agents are not available, activated prothrombin complex concentrates can be used for dabigatran-associated bleeding, and four-factor prothrombin complex concentrates can be used for rivaroxaban- or apixaban-associated bleeding.

COMMENT

Although it is reassuring that DOAC reversal agents are now available, guidance on their rational use is needed, given their cost, limited availability, and associated risk for thrombosis. The authors suggest a need for multidisciplinary stewardship programs to assist with proper use of reversing agents. Ideally, hospital systems will help with the evolution of the Coumadin clinic toward broader anticoagulation monitoring services that support patients treated with DOACs. Although laboratory monitoring is seldom needed, patients treated with DOACs still require careful monitoring and guidance with difficult decisions, including regarding the need for urgent reversal.

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