Direct oral anticoagulant reversal: how, when and issues faced

Introduction: The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. Areas covered: In the current review, risk of major bleeding in patients taking NOACs and general approaches to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed. Expert commentary: Due to short half-life of NOACs compared to warfarin, discontinuation of drug, mechanical compression, and volume substitution are considered to be sufficient measures in most of bleeding cases. In case of life-threatening bleeding or urgent surgery, hemostasis can be achieved with non-specific reversal agents (prothrombin complex concentrates) in patients treated with factor Xa inhibitor until specific antidotes (andexanet α and ciraparantag) will receive approval. Thus far, idarucizumab has been the only reversal agent approved for dabigatran.