What is the reversal treatment for Eliquis (apixaban) in cases of life-threatening bleeding?

Reversal of Apixaban (Eliquis) in Life-Threatening Bleeding

For life-threatening bleeding in patients taking apixaban, andexanet alfa is the first-line specific reversal agent and should be administered promptly according to a weight-based protocol. 1, 2

First-Line Reversal Strategy

Andexanet Alfa Administration

• Dosing regimen based on:
  • Last dose of apixaban
  • Timing since last dose 3, 2

Low-Dose Regimen

• For patients who took ≤5 mg of apixaban >8 hours ago:
  • 400 mg IV bolus over 15 minutes
  • Followed by 480 mg IV infusion over 2 hours 1, 2

High-Dose Regimen

• For patients who took >5 mg of apixaban or took apixaban <8 hours ago or unknown timing:
  • 800 mg IV bolus over 30 minutes
  • Followed by 960 mg IV infusion over 2 hours 1, 2

Alternative Reversal Options (If Andexanet Alfa Unavailable)

Four-Factor Prothrombin Complex Concentrate (4F-PCC)

• Dose: 2000 units IV (approximately 25-50 units/kg) 3
• Consider when andexanet alfa is unavailable or contraindicated

Activated Prothrombin Complex Concentrate (APCC)

• May be considered as a third-line option if neither andexanet alfa nor 4F-PCC is available 3

Laboratory Assessment

• Anti-FXa activity: Most accurate test to measure apixaban activity and reversal efficacy 1
• Thresholds for reversal:
  • Consider reversal for major bleeding with apixaban level >50 ng/mL
  • For emergency surgery with high bleeding risk, consider reversal with level >30 ng/mL 1

Important Clinical Considerations

Efficacy

• Andexanet alfa rapidly (within minutes) reduces anti-FXa activity by >90% 3, 4
• Hemostatic efficacy (excellent or good hemostasis at 12 hours) achieved in approximately 80% of patients 5

Monitoring After Reversal

• Monitor for rebound anticoagulation: Significant apixaban concentrations may reappear after andexanet alfa administration ends 1
• Duration of effect: The reversal effect is maintained during the 2-hour infusion but may diminish afterward 3

Thrombotic Risk

• Thrombotic events: 11-18% risk within 30 days after andexanet alfa administration 1, 6
• This is due to temporary inhibition of tissue factor pathway inhibitor 3, 1
• Resume anticoagulation: As soon as medically appropriate after bleeding is controlled 7

Indications for Reversal

Reversal of apixaban is indicated in:

• Life-threatening bleeding (intracranial hemorrhage, uncontrollable hemorrhage)
• Bleeding into critical organs (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal)
• Persistent major bleeding despite local hemostatic measures
• Need for urgent high-risk surgery/intervention that cannot be delayed 3

Situations Where Reversal Is Not Indicated

• Elective surgery
• Gastrointestinal bleeds responding to supportive measures
• High drug levels without associated bleeding
• Need for surgery that can be delayed for drug clearance (≥8 hours with normal renal function) 3

Practical Pitfalls to Avoid

1. Delaying reversal: Don't wait for laboratory confirmation in life-threatening bleeding situations 3
2. Inadequate monitoring: Continue clinical and laboratory monitoring after andexanet alfa administration due to potential rebound anticoagulation 1
3. Neglecting thrombotic risk: Balance reversal against potential prothrombotic effects, particularly with andexanet alfa 1
4. Inappropriate dosing: Using low-dose regimen when high-dose is indicated based on timing or dose of last apixaban administration 2
5. Failure to restart anticoagulation: Resume anticoagulation as soon as medically appropriate to prevent thrombotic events 7