Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH

J Thromb Haemost. 2024 Oct;22(10):2889-2899. doi: 10.1016/j.jtha.2024.07.009. Epub 2024 Jul 17.

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.

Keywords: andexanet; bleeding; direct oral anticoagulants; factor XI inhibitors; idarucizumab; prothrombin complex concentrates.

Publication types

  • Review
  • Practice Guideline

MeSH terms

  • Administration, Oral
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Arginine / analogs & derivatives
  • Blood Coagulation* / drug effects
  • Dabigatran / administration & dosage
  • Dabigatran / adverse effects
  • Factor Xa / therapeutic use
  • Factor Xa Inhibitors* / administration & dosage
  • Factor Xa Inhibitors* / adverse effects
  • Factor Xa Inhibitors* / therapeutic use
  • Hemorrhage* / chemically induced
  • Humans
  • Piperazines
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Risk Factors
  • Treatment Outcome

Substances

  • Factor Xa Inhibitors
  • PRT064445
  • idarucizumab
  • Antibodies, Monoclonal, Humanized
  • Recombinant Proteins
  • Anticoagulants
  • Dabigatran
  • Factor Xa
  • PER977
  • Arginine
  • Piperazines