What is the recommended approach for reversing warfarin (anticoagulant) in cases of intracranial bleeding?

Warfarin Reversal in Intracranial Hemorrhage

For patients with intracranial hemorrhage on warfarin therapy, urgent reversal with 4-factor prothrombin complex concentrate (PCC) plus intravenous vitamin K 10 mg is strongly recommended as the first-line treatment. 1

Initial Management

• Immediately discontinue warfarin when intracranial hemorrhage is present or suspected 1
• Check INR level as soon as possible to guide reversal strategy 1
• For patients with INR ≥ 1.4, administer vitamin K 10 mg IV along with PCC 1
• Time is critical - implement rapid reversal protocols to ensure correction of coagulopathy within 4 hours of admission 1

Recommended Reversal Protocol

First-Line Therapy:

• 4-factor PCC (weight-based dosing according to INR) 1
  • Preferred over 3-factor PCC due to more complete factor replacement 1
  • Offers rapid INR correction (within 1-2 hours) 2
  • Does not require cross-matching or thawing 1
  • Can be administered in smaller volumes over shorter periods (20-30 minutes) 1

Concurrent Administration:

• Vitamin K 10 mg IV (administered slowly over 20-30 minutes) 1
  • Essential for durable reversal of anticoagulation 1
  • Prevents INR rebound after initial correction 1
  • Monitor INR at 24-48 hours and consider redosing vitamin K if INR remains ≥1.4 1

Alternative When PCC Unavailable:

• Fresh Frozen Plasma (FFP) 10-15 mL/kg IV 1
  • Less effective and slower than PCC 3, 4
  • Requires blood type cross-matching, thawing, and longer infusion times 1
  • May not achieve complete INR correction 3

Comparative Effectiveness

• PCC provides significantly faster INR correction compared to FFP (65-98 minutes vs. 256-307 minutes) 4, 2
• PCC achieves more complete INR normalization than FFP (mean post-treatment INR 1.3 vs. 2.3) 3
• PCC allows earlier surgical intervention when needed (159 minutes vs. 307 minutes) 2
• PCC administration is associated with improved outcomes in elderly patients with traumatic intracranial hemorrhage 1

Monitoring and Follow-up

• Recheck INR within 30-60 minutes after PCC administration to confirm adequate reversal 1, 5
• Monitor for INR rebound within 24-48 hours, especially with shorter-acting reversal agents 1, 4
• If INR remains elevated (≥1.4) after initial treatment, consider additional vitamin K 10 mg IV 1

Special Considerations

• Not recommended: Recombinant activated factor VII (rFVIIa) as first-line therapy due to thrombotic risk and lack of FDA approval for this indication 1, 6
• Consider risks of thromboembolism when reversing anticoagulation (7.2-12% within 30 days) 1
• Decision on when to restart anticoagulation should be carefully weighed against risk of thromboembolism (3-5% 30-day risk of ischemic stroke after discontinuation) 1, 6

Common Pitfalls to Avoid

• Delaying reversal while waiting for FFP preparation - time to correction is critical for preventing hematoma expansion 1, 2
• Relying solely on vitamin K without concurrent PCC or FFP administration 1
• Using 3-factor PCC when 4-factor PCC is available (4-factor provides more complete factor replacement) 1
• Failing to administer vitamin K concurrently with PCC/FFP, which can lead to INR rebound 1, 4
• Overlooking the need for follow-up INR monitoring to detect rebound coagulopathy 1, 5