What is the recommended approach for reversing Eliquis (apixaban) with Kcentra (4-factor prothrombin complex concentrate) in cases of life-threatening bleeding?

Reversal of Apixaban (Eliquis) with Kcentra (4-Factor PCC) in Life-Threatening Bleeding

For life-threatening bleeding in patients taking apixaban (Eliquis), andexanet alfa is the first-line specific reversal agent, but when unavailable, Kcentra (4-factor prothrombin complex concentrate) at a dose of 50 U/kg is recommended as an alternative. 1, 2

First-Line Reversal Strategy

• Andexanet alfa is the FDA-approved specific reversal agent for apixaban-associated life-threatening bleeding 1
• Dosing depends on timing and last dose of apixaban:
  • Low dose: 400 mg IV bolus over 15 minutes followed by 480 mg infusion over 2 hours 1
  • High dose: 800 mg IV bolus over 30 minutes followed by 960 mg infusion over 2 hours 1

When Andexanet Alfa is Unavailable: Using Kcentra (4F-PCC)

• When andexanet alfa is unavailable, 4-factor PCC (Kcentra) should be administered at 50 U/kg (maximum dose 4,000 units) 2
• 4F-PCC has been shown to effectively restore endogenous thrombin potential (ETP) to pre-apixaban levels within 4 hours of administration, compared to 45 hours with placebo 3
• Clinical studies show that 4F-PCC achieves hemostatic effectiveness in approximately 72.4% of patients with major bleeding on apixaban 4

Indications for Reversal

Reversal of apixaban should be considered in:

• Life-threatening bleeding (e.g., intracranial hemorrhage) 1
• Bleeding in critical organs or closed spaces (intraspinal, intraocular, pericardial, pulmonary, retroperitoneal) 1
• Severe bleeding with hemodynamic instability 2
• Bleeding causing a decrease in hemoglobin of ≥2 g/dL or requiring ≥2 units of RBCs 2

Laboratory Assessment

• Early assessment of laboratory coagulation tests is recommended before reversal 2
• Anti-Xa activity assays are preferred for quantifying apixaban levels 1
• A threshold of >50 ng/mL is generally considered clinically significant for patients with serious bleeding 2, 1
• Standard coagulation tests (PT, INR, aPTT) have limited utility in assessing the anticoagulant effect of apixaban 3

Administration Protocol for Kcentra (4F-PCC)

1. Confirm life-threatening bleeding in a patient taking apixaban 2
2. Administer Kcentra at 50 U/kg IV (maximum 4,000 units) 2
3. Continue standard hemostatic measures (compression, surgical intervention if needed) 2
4. Monitor for clinical response and consider repeat dosing if bleeding continues 2

Monitoring After Reversal

• Monitor for thromboembolic events, which occur in approximately 10% of patients receiving reversal agents 1, 5
• After 4F-PCC administration, ETP levels may increase above pre-apixaban levels (34-51% increase) and remain elevated (21-27% increase) for up to 69 hours 3
• Resume anticoagulation as soon as medically appropriate to reduce thrombotic risk 6

Important Considerations and Caveats

• Comparative studies suggest andexanet alfa may provide better hemostatic effectiveness (85.8% vs. 68.1%) and decreased mortality (7.9% vs. 19.6%) compared to 4F-PCC for intracranial hemorrhage 5
• In vitro studies suggest that activated PCC (aPCC) may be more effective than 4F-PCC in reversing apixaban's anticoagulant effect, but clinical data is limited 7
• Thrombotic complications are a risk with both andexanet alfa and 4F-PCC 6, 5
• Discuss with the primary service managing anticoagulation before fully reversing a patient's anticoagulation 2
• Anticoagulant therapy should be resumed as soon as medically appropriate to prevent thrombotic events 6

Alternative Hemostatic Agents

• Tranexamic acid can be considered as an adjunctive therapy to support hemostasis, though it does not directly reverse the anticoagulant effect 2
• Activated charcoal may be useful if apixaban ingestion occurred within the last 2-4 hours 3