Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants

Thromb Haemost. 2015 Nov 25;114(6):1113-26. doi: 10.1160/TH15-03-0222. Epub 2015 Jul 9.


Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in the prevention and treatment of venous thromboembolism and in the prevention of stroke in patients with non-valvular atrial fibrillation. In phase III clinical trials and meta-analyses, the NOACs were at least as effective as vitamin K antagonists (VKAs) and were associated with a similar or lower incidence of major bleeding, including consistent and significant decreases in intracranial bleeding, although with an increase in gastrointestinal bleeding for some agents compared with VKAs. Subsequent real-world evidence supports these outcomes. Despite this, physicians have concerns about serious bleeding or emergencies because there are no specific reversal agents for the NOACs. However, in clinical trials, patients receiving NOACs generally had similar or better outcomes after these events than those taking VKAs. As with any bleeding, anticoagulant-related bleeding should first be stratified according to severity and location; risk can be minimised by ongoing assessment. Management protocols for NOAC-related bleeding are similar to those for VKAs but should take into account the pharmacological profile of the specific drug. Because of their short half-lives, NOAC-related mild bleeding can often be controlled by temporarily withholding treatment. More severe bleeding requires standard escalating haemodynamic support measures, and non-specific reversal agents can be considered in life-threatening situations, based on limited clinical data. Specific and rapid reversal agents are not currently available for any oral anticoagulant and restoration of coagulation may not necessarily lead to better outcomes. Nevertheless, specific NOAC reversal agents are in development and show promise in healthy volunteers.

Keywords: Bleeding profiles; bleeding management; non-vitamin K oral anticoagulant; real-world data; reversal agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antidotes / chemistry
  • Antidotes / therapeutic use
  • Antithrombins / adverse effects*
  • Antithrombins / pharmacokinetics
  • Antithrombins / therapeutic use
  • Atrial Fibrillation / complications
  • Blood Coagulation Factors / therapeutic use
  • Blood Transfusion
  • Clinical Protocols
  • Clinical Trials, Phase III as Topic
  • Disease Management
  • Drug Design
  • Factor Xa Inhibitors / adverse effects*
  • Factor Xa Inhibitors / pharmacokinetics
  • Factor Xa Inhibitors / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / therapy*
  • Hemostatic Techniques
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / therapy
  • Kidney Failure, Chronic / complications
  • Meta-Analysis as Topic
  • Neoplasms / complications
  • Perioperative Care
  • Postoperative Hemorrhage / chemically induced
  • Postoperative Hemorrhage / prevention & control
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / therapeutic use
  • Renal Dialysis
  • Retrospective Studies
  • Risk Assessment
  • Thrombophilia / drug therapy
  • Thrombophilia / etiology
  • Vulnerable Populations
  • Warfarin / adverse effects


  • Antidotes
  • Antithrombins
  • Blood Coagulation Factors
  • Factor Xa Inhibitors
  • Recombinant Proteins
  • Warfarin