An 85-year-old man on warfarin for atrial fibrillation with intracranial hemorrhage and an INR of 3.4—should he receive intravenous vitamin K and fresh frozen plasma or a 4-factor prothrombin complex concentrate?

Immediate Warfarin Reversal for Intracranial Hemorrhage

This 85-year-old patient with intracranial hemorrhage and INR 3.4 requires immediate administration of 4-factor prothrombin complex concentrate (PCC) 35-50 U/kg IV plus vitamin K 10 mg IV by slow infusion—not fresh frozen plasma. 1, 2

Why PCC is Mandatory Over FFP

PCC achieves INR correction within 5-15 minutes, whereas FFP requires several hours, making it the only appropriate choice when intracranial hemorrhage expansion threatens life. 1, 2 In the landmark INCH trial, 67% of PCC-treated patients achieved INR ≤1.2 within 3 hours versus only 9% with FFP. 2 More critically, PCC reduced hematoma expansion to 18.3% compared with 27.1% for FFP in patients with intracranial hemorrhage. 2

• PCC contains roughly 25-times the concentration of vitamin K-dependent clotting factors compared with plasma, allowing rapid correction in minimal volume. 1, 2
• No ABO blood type matching is required, eliminating delays that could prove fatal in this time-sensitive emergency. 1, 2
• Minimal risk of fluid overload compared with the large volumes (10-15 mL/kg) required for FFP. 1
• Room-temperature storage as lyophilized powder allows immediate bedside reconstitution without thawing delays. 2

Specific Dosing Protocol for This Patient

For INR 3.4, administer 4-factor PCC at 35 U/kg IV (the dose for INR range 2-4 is 25 U/kg, but for INR approaching 4.0, use 35 U/kg). 1, 2 The maximum total dose is capped at 5,000 units (equivalent to 100 kg body weight). 2

Concurrently give vitamin K 10 mg IV by slow infusion over 30 minutes. 1, 2 This is mandatory because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of vitamin K-dependent factors for sustained reversal. 1, 2

• Target INR is <1.5 for intracranial hemorrhage. 1, 2
• Recheck INR 15-60 minutes after PCC administration to confirm adequate correction. 1, 2
• Monitor INR serially every 6-8 hours for the next 24-48 hours, as some patients require additional correction. 1

Why FFP is Inadequate

FFP is only recommended if PCC is unavailable, which should be an extremely rare circumstance in modern hospitals. 1 The time delay with FFP directly translates to increased mortality:

• 30-40% of intracranial hemorrhages expand during the first 12-36 hours, and elevated INR enhances this expansion. 2
• In one study, median time to INR normalization was 85 minutes with PCC versus 10 hours in patients who died. 3
• FFP reversal took more than twice as long compared with PCC (1933 ± 905 minutes versus 980 ± 1021 minutes to reach INR 1.3). 4

Critical Safety Considerations

Anaphylactoid reactions to IV vitamin K occur in 3 per 100,000 doses, potentially causing cardiac arrest, severe hypotension, or bronchospasm. 1, 2 Slow infusion over 30 minutes minimizes this risk. 1, 2

PCC use increases thrombotic risk during the recovery period (7.2-12% within 30 days), so thromboprophylaxis must be considered as early as possible after bleeding control. 1, 2 However, the risks of not reversing anticoagulation in intracranial hemorrhage vastly outweigh thrombotic risks. 5

Do not exceed 10 mg of vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days. 1, 2

Common Pitfalls to Avoid

• Never rely on vitamin K alone for urgent reversal—it requires 4-6 hours to begin lowering INR, far too slow when hematoma expansion threatens herniation. 2
• Never use recombinant factor VIIa (rFVIIa) as first-line therapy—it carries a 5% thromboembolic event rate and is not recommended by guidelines. 1, 5
• Never delay reversal while awaiting laboratory confirmation in life-threatening intracranial hemorrhage—immediate treatment is mandated. 2
• Do not restart warfarin until bleeding is completely controlled, the patient is hemodynamically stable, and at least 7-10 days have passed. 2

Resuming Anticoagulation

For atrial fibrillation, the 30-day risk of ischemic stroke after warfarin discontinuation is 2.1%, whereas recurrent intracranial hemorrhage risk is zero when anticoagulation is appropriately withheld during hospitalization. 2 Studies show warfarin can be safely held for a median of 10 days with minimal thromboembolic risk. 2