How to reverse an International Normalized Ratio (INR) of 15 with fresh frozen plasma (FFP)?

Reversal of INR 15 with Fresh Frozen Plasma (FFP)

For an INR of 15, a combination of four-factor prothrombin complex concentrate (PCC) and vitamin K is strongly recommended over FFP alone due to faster reversal time and reduced mortality. 1

Initial Assessment and Management

1. Assess for active bleeding and hemodynamic stability

   • Vital signs (blood pressure, heart rate)
   • Clinical signs of bleeding (visible blood, hematomas, neurological changes)
   • Hemoglobin level and need for blood transfusion

2. Immediate interventions:

   • Hold warfarin immediately
   • Establish IV access with large-bore catheters
   • Draw baseline coagulation studies (repeat INR, PTT, fibrinogen)
   • Type and cross-match for blood products

Reversal Protocol for INR 15

First-line therapy:

• Four-factor PCC at 50 units/kg IV (maximum 5000 units) 1, 2
• Vitamin K 10 mg IV (infuse slowly over 20-30 minutes) 1
• Fresh frozen plasma 10-15 mL/kg if PCC is unavailable 1

Dosing considerations:

• For INR >6, the recommended PCC dose is 50 units/kg 2
• Higher doses of FFP (15-30 mL/kg) may be required for INR values as high as 15

Monitoring:

• Repeat INR 15-60 minutes after PCC administration 1
• Continue serial INR monitoring every 6-8 hours for 24-48 hours 1
• If repeat INR remains ≥1.4 within 24-48 hours after initial PCC dosing, consider additional FFP 1

Advantages of PCC over FFP alone

1. Faster INR correction: PCC corrects INR in 15-30 minutes vs. several hours with FFP alone 1, 3, 4
2. Lower volume: PCC delivers concentrated clotting factors without fluid overload risk
3. Reduced transfusion requirements: PCC + FFP reduces need for blood products compared to FFP alone 3
4. Lower mortality: Combined PCC + FFP approach shows reduced mortality compared to FFP alone (25% vs 33%) 3

FFP-only Approach (if PCC unavailable)

If using FFP alone, consider:

• Higher volume: 15-30 mL/kg (approximately 4-8 units for a 70kg patient)
• Immediate administration: Every 30-minute delay decreases odds of INR reversal within 24 hours by 20% 5
• Anticipate slower correction: Mean time to INR correction with FFP alone is approximately 30 hours vs. 17 hours with PCC 4

Important Caveats

1. Thrombotic risk: Monitor for thrombotic complications, especially with repeated PCC dosing 1
2. Vitamin K is essential: Always administer vitamin K with PCC or FFP to sustain the reversal effect 1
3. FFP limitations: FFP alone may be ineffective for INR values >1.7 6
4. Time sensitivity: Rapid administration is critical - shorter time to first FFP dose correlates with successful INR reversal 5
5. Volume considerations: FFP-only approach requires large volumes (>1L) which may not be tolerated in patients with cardiac or renal disease

Follow-up Management

• Continue INR monitoring until stable in therapeutic range
• Investigate cause of supratherapeutic INR
• Consider lower target INR (2.0-2.5) when resuming therapy, especially in older adults 2
• Implement more frequent INR monitoring after resumption of therapy

Remember that an INR of 15 represents a critical anticoagulation level with significant bleeding risk requiring immediate intervention. The combination of PCC and vitamin K provides the most rapid and effective reversal strategy.