What is the management plan for a patient on Eliquis (apixaban) who has experienced a brain hemorrhage?

Management of Brain Hemorrhage in a Patient on Apixaban

For a patient on apixaban (Eliquis) who has experienced a brain hemorrhage, immediately stop the anticoagulant, administer andexanet alfa as the specific reversal agent, and provide supportive care while delaying anticoagulation restart for at least 4 weeks. 1

Immediate Management

Step 1: Stop Anticoagulation and Assess Bleeding Severity

• Immediately discontinue apixaban 1
• Determine if bleeding meets criteria for major bleeding:
  • Bleeding at a critical site (intracranial hemorrhage is considered critical)
  • Hemodynamic instability
  • Clinically overt bleeding with hemoglobin decrease ≥2 g/dL or requiring ≥2 units of RBCs

Step 2: Administer Reversal Agent

• First-line therapy: Administer andexanet alfa 1

  • Low dose: 400 mg IV bolus followed by 4 mg/min infusion for up to 120 minutes (480 mg) if:
    • Last apixaban dose was ≤5 mg and taken ≥8 hours prior, OR
    • Last apixaban dose was ≤5 mg taken <8 hours prior or timing unknown
  • High dose: 800 mg IV bolus followed by 8 mg/min infusion for up to 120 minutes (960 mg) if:
    • Last apixaban dose was >5 mg taken <8 hours prior, OR
    • Unknown dose taken <8 hours prior

• Alternative if andexanet alfa unavailable: Administer prothrombin complex concentrate (PCC) or activated PCC 1, 2

  • 4-factor PCC at 25-50 U/kg has shown good hemostatic efficacy in 89% of cases 2

Step 3: Additional Measures

• Provide local therapy/manual compression if applicable
• Provide supportive care and volume resuscitation
• Consider activated charcoal for known recent ingestion (within 2-4 hours) 1
• Assess for and manage comorbidities that could contribute to bleeding (e.g., thrombocytopenia, uremia, liver disease)
• Consider surgical/procedural management of bleeding site if indicated

Monitoring and Follow-up

Neurological Monitoring

• Frequent neurological assessments
• Serial CT scans to monitor for hematoma expansion
• Monitor for signs of increased intracranial pressure

Laboratory Monitoring

• Complete blood count
• Renal function tests (affects apixaban clearance)
• Coagulation parameters (although standard tests may not accurately reflect apixaban activity)

Long-term Management and Anticoagulation Restart

When to Consider Restarting Anticoagulation

• Delay restart of anticoagulation for at least 4 weeks after brain hemorrhage 1
• Factors affecting decision to restart:
  • Location of hemorrhage (lobar vs. non-lobar)
  • Patient's thrombotic risk
  • Risk of recurrent bleeding

Recommendations Based on Hemorrhage Location

• For lobar ICH: Avoidance of long-term anticoagulation is probably recommended due to relatively high risk of recurrence 1
• For non-lobar ICH: Anticoagulation might be considered, particularly with strong indications 1

Risk Factors for ICH Recurrence to Consider

• Lobar location of the initial ICH
• Older age
• Presence and number of microbleeds on gradient echo MRI
• Ongoing anticoagulation
• Presence of apolipoprotein E ε2 or ε4 alleles 1

Special Considerations

Blood Pressure Management

• Implement strict blood pressure control immediately after ICH onset
• Long-term goal of BP <130 mm Hg systolic and 80 mm Hg diastolic 1

Alternative Anticoagulation Options

• The usefulness of DOACs including apixaban in patients with atrial fibrillation and past ICH to decrease risk of recurrence is uncertain 1
• Consider left atrial appendage closure as an alternative to anticoagulation in patients with atrial fibrillation at high risk for both thromboembolism and recurrent ICH

Lifestyle Modifications

• Recommend avoidance of alcohol use greater than 2 drinks per day
• Advise against tobacco use and illicit drug use
• Treat obstructive sleep apnea if present 1

Pitfalls to Avoid

• Delaying administration of reversal agents in critical bleeding
• Restarting anticoagulation too early (before 4 weeks) after ICH
• Failing to control blood pressure, which increases risk of recurrent ICH
• Overlooking the higher risk of recurrence with lobar hemorrhages
• Neglecting to consider alternatives to anticoagulation in high-risk patients

The management of patients on apixaban with brain hemorrhage requires prompt action to reverse anticoagulation and careful consideration of long-term strategies to balance the risks of thromboembolism against recurrent bleeding.