Antidotes for reversal of direct oral anticoagulants

The main advantage of the direct oral anticoagulants over vitamin K antagonists is reduced rates of major bleeding, especially intracranial hemorrhage. While use of different clotting factor supplements have been used in patients with direct oral anticoagulant induced major bleeding or when there is need for urgent surgery, the lack of preclinical and clinical data are concerning. Idarucizumab is a specific antibody developed with a 350-fold greater affinity for dabigatran than its pharmacologic target thrombin. Andexanet is a modified factor Xa molecule that binds the direct and indirect Xa inhibitors without being enzymatically active. Ciraparantag, has potential to reverse the anticoagulant activity of multiple agents. The pharmacology, preclinical, and clinical data that have developed these specific antidotes are reviewed in this manuscript. (C) 2019 Elsevier Inc. All rights reserved.