Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH
Jerrold H. Levy 1), Joseph R. Shaw 2), Lana A. Castellucci 3), Jean M. Connors 4), James Douketis 5), Edelgard Lindhoff-Last 6), Bianca Rocca 7) 8), Charles Marc Samama 9), Deborah Siegal 3) Jeffrey I. Weitz 10)
1) Department of Anesthesiology, Critical Care, and Surgery, Duke University School of Medicine, Durham, North Carolina, USA
2) Department of Medicine, Division of Hematology, University of Ottawa, Ottawa, Ontario, Canada
3) Department of Medicine, Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Ontario, Canada
4) Hematology Division Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
5)Department of Medicine, Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
6) Department of Vascular Medicine and Hemostaseology, Coagulation Research Centre Bethanien Hospital, Frankfurt, Germany
7) Department of Safety and Bioethics-Section of Pharmacology, Catholic University School of Medicine, Rome, Italy
8) NeuroFarBa Department, University of Florence, Florence, Italy
9) Department of Anaesthesia, Intensive Care and Perioperative Medicine, Groupement Hospitalier Universitaire Assistance Publique – Hôpitaux de Paris Centre, Université Paris Cité, Paris, France
10) Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
Abstract
The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs than with vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet alfa and idarucizumab are the currently approved specific reversal agents for oral factor (F)Xa inhibitors and dabigatran, respectively. Our prior guidance document was published in 2016, but with more information available on the utility and increased use of these reversal agents and other bleeding management strategies, we have updated this International Society on Thrombosis and Haemostasis guidance document on DOAC reversal. In this narrative review, we compare the mechanism of action of specific and nonspecific reversal agents, review the clinical data supporting their use, and provide guidance on when reversal is indicated. In addition, we briefly discuss the reversal of oral FXIa inhibitors, a new class of DOACs currently under clinical development.