Reversal agents for severe bleeding associated with direct oral anticoagulants

Abstract

Direct oral anticoagulants (DOACs) have demonstrated a positive benefit-risk balance compared with vitamin K antagonists in both clinical trials and real-world studies. However, with increased DOAC use, the risk of bleeding should not be underestimated. In clinical practice, the annual rate of DOAC-related major bleeding is between approximately 1.5% and 3.5%. The outcome of major bleeds was similar or better in patients receiving DOACs than in those taking vitamin K antagonists. Due to their short half-lives, supportive measures are sufficient to manage most bleeds in patients receiving DOACs. Anticoagulant reversal should only be considered with life-threatening bleeds or with serious bleeds that fail to respond to usual measures. Effective strategies to reverse the anticoagulant effects of DOACs are now available. Idarucizumab has been approved for dabigatran reversal and andexanet alfa was recently granted approval for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding events. Other reversal agents (e.g. ciraparantag for heparins and DOACs) are under development. Non-specific prohemostatic agents (e.g. prothrombin complex concentrate) can counteract the anticoagulant action of DOACs in emergency situations, when specific reversal agents are unavailable. However, specific reversal agents are efficacious and safe and should be preferred when available.