A 67-year-old female with a history of deep venous thrombosis of the right leg on warfarin presents with headache after an accidental ground level fall. Head CT is shown. INR is 3.0. She is alert and oriented with a small golf ball-sized hematoma to the forehead. In addition to vitamin K administration, which of the following is the next best step in management for this patient?

Answer: B. Four-factor prothrombin complex concentrate

A. Activated recombinant factor VII INCORRECT
Activated recombinant factor VII (rFVIIa) reverses warfarin anticoagulation within 1hour, often normalizing INR within 10-15min. However, rFVIIa has a short half-life (1-2 hours), which is shorter than the 4-6 hours required for IV vitamin K to take full effect. Repeated rFVIIa dosing is often required and, given the availability of 4-factor prothrombin concentrate (4-factor PCC), rFVIIa is not the best option available.

B. Four-factor prothrombin complex concentrate CORRECT
4-factor prothrombin complex concentrate (PCC) is made from pooled human plasma and contains factors II, VII, IX, X (as well as some amounts proteins C and S). In warfarin-associated hemorrhage, 4-factor PCC reverses INR within 15 minutes and reverses anticoagulation for 6-8 hours (enough time for IV vitamin K to take full effect), meaning a single dose of PCC appears to be sufficient (unlike rFVIIa). Currently, this is the best option available to acutely reverse and sustain the reversal of this patient’s elevated INR in the setting of the subarachnoid hemorrhage demonstrated in the head CT image.

C. Fresh frozen plasma INCORRECT
For life threatening warfarin-associated hemorrhage, there are two main goals: replace the depleted factors in the shorter-term and restore native synthesis via vitamin K for the longer-term. Fresh frozen plasma (15-30ml/kg) is a suboptimal choice with correction of INR taking up to 48hours, along with significant transfusion-related and volume-related complications.

D. Observe and repeat head CT in 4 hours INCORRECT
This head CT demonstrates subarachnoid hemorrhage. In the setting of warfarin-associated hemorrhage, this is a life-threatening bleed that needs to be acutely reversed with immediate coagulation factor repletion, in addition to sustained warfarin reversal (via vitamin K). Vitamin K takes 4-6 hours to take full effect, so immediate factor repletion is indicated, and 4-factor prothrombin complex concentrate is the best available answer choice. While a repeat head CT is indicated to evaluate the progression of the intracranial hemorrhage, vitamin K alone is incorrect. 

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