What is the role of Fresh Frozen Plasma (FFP) transfusion in managing intracranial bleed with deranged International Normalized Ratio (INR)?

Role of FFP Transfusion in Intracranial Hemorrhage with Deranged INR

Prothrombin Complex Concentrates (PCCs) are strongly preferred over Fresh Frozen Plasma (FFP) for rapid reversal of anticoagulation in patients with intracranial hemorrhage and elevated INR. 1

Anticoagulation Reversal in Intracranial Hemorrhage

First-Line Treatment

• For patients with VKA-associated intracranial hemorrhage with INR ≥1.4:
  • Four-factor PCC (dosing based on weight and INR) 1
  • Vitamin K 10 mg IV (as adjunct therapy) 1
  • FFP should only be used if PCC is not available 1

Rationale for PCC over FFP

PCCs offer several critical advantages over FFP in the emergency setting of intracranial hemorrhage:

1. Speed of correction: PCCs correct INR within minutes versus hours for FFP 1
2. Lower volume: PCCs require significantly smaller infusion volumes (typically <50mL vs ~1L for FFP) 1
3. No blood typing needed: PCCs don't require ABO compatibility testing 1
4. Reduced complications: Lower risk of transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) 1

A randomized controlled trial comparing 4-factor PCC with FFP in patients with VKA-associated ICH demonstrated:

• 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% of FFP-treated patients 1
• Reduced hematoma expansion with PCC (18.3% vs 27.1%) 1

When to Use FFP

FFP should be considered in the following scenarios:

• When PCCs are unavailable 1
• As a second-line agent if repeat INR remains elevated ≥1.4 after initial PCC dosing 1
• In resource-limited settings where PCCs are not accessible 1

Practical Approach to Management

Immediate Steps

1. Assess severity and obtain baseline information:

   • Check INR, time of last anticoagulant dose, renal function 1
   • Note: Do not delay treatment waiting for INR results if clinical suspicion is high 1

2. Administer reversal agents:

   • First choice: 4-factor PCC (25-50 IU/kg based on weight and INR) 1
   • Administer vitamin K 10 mg IV concurrently 1
   • If PCC unavailable: FFP 10-15 mL/kg IV 1

3. Monitor response:

   • Repeat INR 15-60 minutes after PCC administration 1
   • Continue serial INR monitoring every 6-8 hours for 24-48 hours 1

Common Pitfalls to Avoid

1. Delayed reversal: Every hour matters in ICH outcomes; do not wait for INR results to initiate reversal therapy 1
2. Omitting vitamin K: Failing to administer vitamin K with PCC can lead to rebound INR elevation 12-24 hours later 1
3. Relying solely on FFP: FFP alone may be insufficient for rapid correction of coagulopathy in ICH 1
4. Inadequate monitoring: Failure to recheck INR after initial correction may miss rebound coagulopathy 1

Special Considerations

Recombinant Factor VIIa (rFVIIa)

Despite some case reports showing efficacy 2, 3, 4, current guidelines recommend against using rFVIIa as first-line therapy for VKA reversal in ICH due to:

• Lack of strong supporting evidence 1
• Higher thrombotic risk compared to PCCs
• Cost considerations

Severity of INR Elevation

For INR >6.0 in patients with intracranial hemorrhage:

• Immediate reversal is required
• In VKA-associated ICH, avoid IV vitamin K alone due to risk of rapid INR drop 1
• Consider combination therapy with PCC and FFP for severe coagulopathy 1

Conclusion

In managing intracranial hemorrhage with deranged INR, rapid reversal of anticoagulation is critical to prevent hematoma expansion and reduce mortality. Four-factor PCCs, combined with vitamin K, provide the fastest and most effective reversal strategy and should be used as first-line therapy whenever available. FFP should be reserved for situations where PCCs are unavailable or as supplemental therapy when initial PCC treatment is insufficient.