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Direct oral anticoagulant-associated bleeding reversal strategies

Direct oral anticoagulant-associated bleeding reversal strategies
Type of bleeding Agent Possible interventions
Life-threatening or imminently fatal bleeding (eg, intracranial, retroperitoneal, compartment syndrome, massive gastrointestinal) Dabigatran (Pradaxa)
  • Idarucizumab
  • Activated PCC* (eg, FEIBA)
  • Antifibrinolytic agent (eg, tranexamic acid, epsilon-aminocaproic acid)
  • Anticoagulant discontinuation
  • Oral activated charcoal (if last dose within prior two hours)
  • Hemodialysis
  • RBC transfusions if needed for anemia
  • Platelet transfusions if needed for thrombocytopenia or impaired platelet function (eg, due to aspirin)
  • Surgical/endoscopic intervention if appropriate
Rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Lixiana)
  • Andexanet alfa (AndexXa) or a 4-factor unactivated PCC (eg, Kcentra)
  • Antifibrinolytic agent (eg, tranexamic acid, epsilon-aminocaproic acid)
  • Anticoagulant discontinuation
  • Oral activated charcoal (if last dose recent enough)
  • RBC transfusions if needed for anemia
  • Platelet transfusions if needed for thrombocytopenia or impaired platelet function (eg, due to aspirin)
  • Surgical/endoscopic intervention if appropriate
Minor bleeding (eg, epistaxis, uncomplicated soft tissue bleeding, minor [slow] gastrointestinal bleeding) Dabigatran (Pradaxa)
  • Local hemostatic measures
  • Possible anticoagulant discontinuation
    • Half-life (normal renal function): 12 to 17 hours
  • Possible antifibrinolytic agent (eg, tranexamic acid, epsilon-aminocaproic acid)
Rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Lixiana)
  • Local hemostatic measures
  • Possible anticoagulant discontinuation
    • Half-lives (normal renal function):
      • Rivaroxaban 5 to 9 hours
      • Apixaban 8 to 15 hours
      • Edoxaban 6 to 11 hours
  • Possible antifibrinolytic agent (eg, tranexamic acid, epsilon-aminocaproic acid)
The table describes measures that may be used to manage bleeding associated with DOACs. Clinical judgment is essential in all cases of DOAC-associated bleeding in order to assess the risks of bleeding and weigh these against the risks of thrombosis if anticoagulation is discontinued or reversed. Refer to UpToDate topics on the use of direct thrombin inhibitors and direct factor Xa inhibitors and management of DOAC-associated bleeding for further details and dosing. The onset of all of the agents discussed herein is approximately 2 to 4 hours.
PCC: prothrombin complex concentrate; FEIBA: factor eight inhibitor bypassing activity; RBC: red blood cell; DOAC: direct oral anticoagulant.
* Use activated PCC only if idarucizumab is unavailable and/or if continued bleeding is reasonably likely to be fatal within hours.
¶ The anticoagulant effect of these agents (especially dabigatran) will dissipate more slowly as renal function declines. Severe hepatic failure may also prolong the half-life for apixaban, edoxaban, and rivaroxaban.
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