What are the options for reversing apixaban (Factor Xa inhibitor)?

Reversal Options for Apixaban

Andexanet alfa is the first-line specific reversal agent for apixaban in cases of life-threatening or uncontrolled bleeding. 1, 2

Specific Reversal Agents

Andexanet Alfa (First-Line)

• Mechanism: Recombinant modified factor Xa protein that acts as a decoy, binding to apixaban and removing it from circulation 1
• Dosing: Based on timing and dose of last apixaban administration:
  • Low dose: 400 mg IV bolus over 15 minutes followed by 480 mg IV infusion over 2 hours
  • High dose: 800 mg IV bolus over 30 minutes followed by 960 mg IV infusion over 2 hours 1
• Efficacy: Reduces anti-FXa activity by approximately 92% for apixaban and achieves excellent or good hemostasis in 80% of patients with major bleeding 3, 2
• Timing: Rapidly reverses anticoagulant effect within minutes of administration 2, 4
• Indications for use:
  • Life-threatening bleeding (e.g., intracranial hemorrhage)
  • Bleeding into critical organs or closed spaces
  • Persistent major bleeding despite local hemostatic measures
  • Emergency surgery with high bleeding risk 1

Alternative Options (When Andexanet Alfa Unavailable)

Prothrombin Complex Concentrate (PCC)

• Four-factor PCC: 25-50 IU/kg IV 1, 3
• Efficacy: Less effective than andexanet alfa but can provide partial reversal
• Advantages: More widely available, lower cost
• Disadvantages: Non-specific reversal, potential thrombotic risk 3

Other Agents Under Development

• Ciraparantag (PER977): Synthetic small molecule that binds to apixaban via hydrogen bonds
  • Currently in clinical development
  • Binds to multiple anticoagulants including apixaban 1
  • Not yet FDA approved 5

Laboratory Assessment

• Anti-FXa assay: Most accurate test to measure apixaban activity
  • Reversal should be considered for patients with major bleeding and apixaban level >50 ng/mL
  • For emergency surgery with high bleeding risk, consider reversal with level >30 ng/mL 1
• Important note: Standard anti-FXa assays may not accurately assess reversal after andexanet administration due to in vitro dissociation 1

Clinical Decision Algorithm for Apixaban Reversal

1. Assess bleeding severity:

   • Life-threatening (intracranial, expanding hematoma)
   • Critical organ/closed space (intraspinal, intraocular, retroperitoneal)
   • Persistent despite local measures
   • Non-critical but clinically significant

2. Determine if reversal is indicated:

   • For life-threatening bleeding: Proceed with reversal immediately
   • For non-life-threatening: Consider if apixaban level >50 ng/mL (if testing available)
   • For emergency surgery: Consider if apixaban level >30 ng/mL and surgery cannot be delayed

3. Select reversal agent:

   • First choice: Andexanet alfa
   • If unavailable: Four-factor PCC (25-50 IU/kg)

4. Post-reversal monitoring:

   • Monitor for thrombotic events (11.1% risk within 30 days) 6
   • Consider restarting anticoagulation 7-14 days after confirmed hemostasis 3

Important Considerations and Pitfalls

• Do not use reversal agents for:

  • Elective surgery
  • Minor bleeding manageable with local measures
  • High drug levels without associated bleeding
  • Procedures that can be delayed for drug clearance 1

• Thrombotic risk: Andexanet alfa administration carries risk of thrombotic events (approximately 11-18% within 30 days) due to temporary inhibition of tissue factor pathway inhibitor 7, 6

• Timing considerations: Apixaban's effect persists for approximately 24 hours after the last dose 8

• Restart considerations: When restarting apixaban after major bleeding, carefully weigh thrombotic risk versus recurrent bleeding risk 3

By following this evidence-based approach, clinicians can effectively manage apixaban-associated bleeding events while minimizing both bleeding and thrombotic complications.