How do you reverse apixaban (Factor Xa inhibitor) in a patient with bleeding?

Reversing Apixaban in Patients with Bleeding

For patients with life-threatening bleeding on apixaban, andexanet alfa is the specific reversal agent of choice, administered as an 800 mg IV bolus followed by a 960 mg IV infusion over 2 hours for recent or unknown timing of last dose. 1

First-Line Reversal Options

Andexanet Alfa

• Mechanism: Recombinant modified human factor Xa protein that binds and sequesters factor Xa inhibitors 1
• Efficacy: Rapidly reduces anti-FXa activity by >90% within minutes 1
• Dosing regimens:
  • High dose (for last dose <7 hours or unknown timing):
    • 800 mg IV bolus over 15-30 minutes
    • Followed by 960 mg IV infusion over 2 hours 1
  • Low dose (for last dose >7 hours):
    • 400 mg IV bolus over 15-30 minutes
    • Followed by 480 mg IV infusion over 2 hours 1
• Duration of effect: Maintained during the 2-hour infusion but may diminish afterward 1
• Safety concerns: Risk of thromboembolic events in 10-18% of patients within 30 days 1

Alternative Option: Prothrombin Complex Concentrate (PCC)

• Use if andexanet alfa is unavailable 1
• Dosing: 50 U/kg 1
• Note: While the FDA label mentions that PCC may be considered, it has not been evaluated in clinical studies 2

Additional Management Strategies

1. Discontinue apixaban in patients with active pathological hemorrhage 2

2. Supportive measures:

   • Local hemostatic measures
   • Fluid resuscitation
   • Blood product support as needed
   • Consider tranexamic acid (1 g IV, repeated every 6 hours if needed)
   • Maintain adequate diuresis to help eliminate apixaban 1

3. Blood transfusion thresholds:

   • Hemodynamically stable patients: Hemoglobin trigger of 70 g/L, target 70-90 g/L
   • Patients with cardiovascular disease: Hemoglobin trigger of 80 g/L, target 100 g/L 1

4. Monitoring:

   • When using PCCs, monitoring anti-factor Xa activity or using clotting tests (PT, INR, aPTT) is not useful and not recommended 2
   • Monitor for rebound anticoagulation after reversal agent administration 1

Important Considerations

• Apixaban's half-life is 6-15 hours with normal renal function but extends to 17 hours with severe renal impairment 1
• The pharmacodynamic effect of apixaban can be expected to persist for at least 24 hours after the last dose 2
• Hemodialysis does not appear to have a substantial impact on apixaban exposure 2
• Activated oral charcoal reduces absorption of apixaban if given shortly after ingestion 2
• Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of apixaban 2
• There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) or systemic hemostatics (desmopressin and aprotinin) in individuals receiving apixaban 2

Post-Reversal Management

• Consider restarting anticoagulation 7-14 days after confirmed hemostasis 1
• Assess the original indication for anticoagulation and the risk of thrombotic events
• Patients remain at risk for delayed intracranial hemorrhage, with risk approximately 0.95% (increasing to 4-4.5% if also on antiplatelet therapy) 1