A review of oral anticoagulants, old and new, in major bleeding and the need for urgent surgery

Trends Cardiovasc Med. 2020 Feb;30(2):86-90. doi: 10.1016/j.tcm.2019.03.004. Epub 2019 Mar 26.


Oral anticoagulants, old and new, are effective therapies for prevention and treatment of venous thromboembolism and reduction of stroke risk in patients with atrial fibrillation. However, blocking elements of the clotting cascade carries an inherent risk of bleeding. Also, anticoagulated patients sometimes require urgent surgery or invasive procedures. This has led to the emergence of a body of scientific literature on the reversal of anticoagulation in these two settings. Traditionally, vitamin K antagonists (VKAs), which indirectly inactivate clotting factors II, VII, IX and X (and natural anticoagulant proteins C and S), had been the mainstay of oral anticoagulation for half a century. Only a few years ago, the US Food and Drug Administration (FDA) approved a specific VKA reversal agent, 4-Factor Prothrombin Complex Concentrate (4F-PCC). The last decade has seen the rise of non-Vitamin K oral anticoagulants (NOACs), which target specific factors, i.e. Factors IIa and Xa. Investigators have rapidly developed reversal agents for these agents as well, idarucizumab for the Factor IIa inhibitor dabigatran (Pradaxa) and andexanet alfa for the entire class of Factor Xa inhibitors (FXaIs), currently four drugs: rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa) and betrixaban (Bevyxxa). Clinicians still use off-label PCC for reversing FXaIs in some settings, and a universal reversal agent, ciraparantag, remains in development. This review summarizes the safety and efficacy of these reversal agents in the setting of anticoagulant-associated major bleeding and the need for urgent surgery.

Keywords: Andexanet alfa; Anticoagulant; Apixaban; Coumadin; Dabigatran; Direct oral anticoagulants; Idarucizumab; Kcentra, 4-factor prothrombin complex concentrate; Major bleeding; Non-Vitamin K oral anticoagulants; Reversal; Rivaroxaban; Vitamin K antagonists; Warfarin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Antidotes / administration & dosage*
  • Antidotes / adverse effects
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Blood Coagulation / drug effects*
  • Blood Loss, Surgical / prevention & control*
  • Clinical Decision-Making
  • Coagulants / administration & dosage*
  • Coagulants / adverse effects
  • Drug Administration Schedule
  • Humans
  • Perioperative Care* / adverse effects
  • Postoperative Hemorrhage / chemically induced
  • Postoperative Hemorrhage / diagnosis
  • Postoperative Hemorrhage / prevention & control*
  • Risk Assessment
  • Risk Factors
  • Stroke / etiology
  • Stroke / prevention & control
  • Treatment Outcome
  • Venous Thromboembolism / blood
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / prevention & control*


  • Anticoagulants
  • Antidotes
  • Coagulants