What is the most appropriate treatment to rapidly reverse coagulopathy in a patient on warfarin (anticoagulant) with an elevated International Normalized Ratio (INR) and potential internal bleeding after a fall?

Prothrombin Complex Concentrate (PCC) IV

For this warfarin-anticoagulated patient with intracranial hemorrhage after a fall and elevated INR, prothrombin complex concentrate (PCC) IV is the most appropriate treatment to rapidly reverse coagulopathy. 1

Rationale for PCC as First-Line Therapy

Four-factor PCC is superior to fresh frozen plasma (FFP) for warfarin reversal in intracranial hemorrhage, achieving INR ≤1.2 within 3 hours in 67% of patients versus only 9% with FFP, and reducing hematoma expansion (18.3% versus 27.1% with FFP). 1

• PCC normalizes INR within 15 minutes of administration compared to hours required for FFP, making it the preferred agent in most national guidelines for serious bleeding. 1
• The Canadian Stroke Best Practice guidelines explicitly recommend PCC over FFP because of its fast onset of action, though FFP and vitamin K can be used as alternatives if PCC is unavailable. 1
• PCC offers additional advantages including no need for ABO blood type matching, minimal risk of fluid overload (particularly important in this patient with severe systolic heart failure), and lower risk of transfusion reactions. 1

Specific Dosing Protocol

Administer 4-factor PCC at a dose based on the patient's INR and body weight: 1, 2

• INR 2-4.0: 25 U/kg IV
• INR 4-6.0: 35 U/kg IV
• INR >6.0: 50 U/kg IV

An alternative fixed-dose regimen of 1500 U can be used for intracranial hemorrhage if weight-based dosing is not immediately feasible. 1

Critical Concurrent Management

Vitamin K 5-10 mg must be administered by slow IV infusion (over 30 minutes) concurrently with PCC. 1, 2

• This is essential because factor VII in PCC has a half-life of only 6 hours, and vitamin K is required to stimulate endogenous production of vitamin K-dependent clotting factors and prevent rebound coagulopathy. 1, 2
• Without vitamin K co-administration, INR can rebound 12-24 hours later, potentially causing hematoma expansion and clinical deterioration. 1

Post-Administration Monitoring

• Check INR within 15-60 minutes after PCC administration to confirm adequate reversal. 2
• If INR remains ≥1.4 within the first 24-48 hours, consider additional vitamin K 10 mg IV. 2
• Monitor INR serially every 6-8 hours for the next 24-48 hours, as some patients require over a week to clear warfarin. 2

Why Other Options Are Inferior

Platelet transfusion is not indicated here—the patient's platelet count is adequate, and the coagulopathy is due to warfarin's effect on clotting factors, not platelet dysfunction. 1

Fresh frozen plasma should only be used if PCC is unavailable, as it requires hours for INR correction, carries risk of volume overload (particularly dangerous in this patient with severe heart failure), and is less effective at preventing hematoma expansion. 1

Idarucizumab is specific for reversing dabigatran (a direct thrombin inhibitor), not warfarin, making it completely inappropriate for this patient. 1

Important Safety Considerations

• PCC carries a thrombotic risk of approximately 2.5-8%, and thromboprophylaxis should be initiated as early as possible after bleeding is controlled. 2
• Target systolic blood pressure <140 mmHg to reduce risk of hematoma expansion. 2
• Four-factor PCC is preferred over 3-factor PCC due to more successful INR reversal with fewer adverse events, particularly lower thrombotic risk. 1

Common Pitfalls to Avoid

• Do not wait for INR results if warfarin use is confirmed and intracranial hemorrhage is present—treatment should be administered immediately based on clinical suspicion. 1
• Do not use vitamin K alone in emergency settings, as it takes 4-24 hours to normalize coagulation. 1
• Do not exceed 10 mg of vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days. 2
• Do not delay neurosurgical consultation while awaiting INR correction—patients can be cleared for the operating room immediately after PCC administration. 3