Managing Bleeding with Eliquis (Apixaban)

Initial Assessment and Management

For life-threatening or critical site bleeding on apixaban, the American College of Cardiology recommends immediately stopping the drug and administering andexanet alfa as the specific reversal agent, with 4-factor prothrombin complex concentrate (4F-PCC) as an alternative if andexanet alfa is unavailable 1, 2
Determine if the bleed is major based on whether ≥1 of the following applies: bleeding at a critical site, hemodynamic instability, or clinically overt bleeding with hemoglobin decrease ≥2 g/dL or transfusion of ≥2 units RBCs, as per the American College of Cardiology guidelines 1, 3
The American College of Cardiology recommends classifying bleeding severity to guide management, with major bleeding defined as bleeding that meets any of the above criteria 1, 3

The American College of Cardiology recommends andexanet alfa as the specific reversal agent for apixaban, dosed as a low-dose regimen (400 mg IV bolus followed by 4 mg/min infusion for 120 minutes) if the last apixaban dose ≤5 mg was taken <8 hours prior, or as a high-dose regimen (800 mg IV bolus followed by 8 mg/min infusion for 120 minutes) if the last apixaban dose >5 mg was taken <8 hours prior 6, 2
If andexanet alfa is unavailable, the American College of Cardiology recommends administering 4-factor prothrombin complex concentrate (4F-PCC) as an alternative, with clinical data demonstrating effective hemostasis in 72.4% of patients with major bleeding on apixaban 1, 2

For major bleeding that is NOT at a critical site or life-threatening, the American College of Cardiology recommends stopping apixaban, providing local therapy/manual compression, and providing supportive care and volume resuscitation 1, 3, 4
The American College of Cardiology also recommends assessing and managing comorbidities contributing to bleeding, and considering surgical/procedural management of the bleeding source 4

Standard coagulation tests (PT, aPTT) are insensitive to apixaban levels, and a prolonged PT suggests clinically important apixaban levels, but a normal PT and aPTT do NOT exclude on-therapy or even above-therapy levels, according to the American College of Cardiology 7
For quantitation of apixaban levels, the American College of Cardiology recommends using an anti-FXa assay calibrated specifically with apixaban, or liquid chromatography-tandem mass spectrometry as an alternative 7, 6

Once the patient is stable, the American College of Cardiology recommends assessing whether to restart anticoagulation, considering factors such as clinical indication for continued anticoagulation, bleeding source control, and absence of contraindications 1, 3, 4
The American College of Cardiology recommends delaying or discontinuing anticoagulation if ≥1 of the following applies: bleed occurred at a critical site, patient is at high risk of rebleeding or of death/disability with rebleeding, source of bleed has not been identified, surgical or invasive procedures are planned, or patient does not wish to restart anticoagulation 1, 3

The American College of Cardiology recommends avoiding the use of vitamin K for apixaban reversal, as it is ineffective for direct oral anticoagulants and only works for warfarin 1, 3
The American College of Cardiology also recommends not delaying resuscitation and local hemostatic measures while obtaining reversal agents, and recognizing high-risk situations for bleeding, such as mild renal failure, advanced age, extremes in body weight, and drug-drug interactions 7