Optimizing the dose of three-factor prothrombin complex concentrate in traumatic brain injury patients on warfarin therapy.

STUDY OBJECTIVE: To determine the percentage of patients with correction of their first international normalized ratio (INR) less than 1.5 after administration of moderate-dose three-factor prothrombin complex concentrate (PCC), 35 IU/kg compared with low-dose PCC, 25 IU/kg.

DESIGN: Retrospective review.

SETTING: Community teaching hospital.

PATIENTS: A total of 42 adult patients diagnosed with warfarin-associated traumatic brain injury (TBI) presented with an INR of 1.5 or more and received at least one dose of PCC during a 19-month study period. The low-dose group received PCC 25 IU/kg from November 2011-July 2012 and the moderate-dose group received PCC 35 IU/kg from August 2012-May 2013.

MEASUREMENTS AND MAIN RESULTS: Of the 42 patients, 25 were in the low-dose group and 17 were in the moderate-dose group. Baseline characteristics were similar between both groups in regard to age, sex, weight, creatinine clearance, weekly warfarin dose, initial INR, initial Glasgow Coma Score, and injury severity score. Of the patients in the low-dose group, 12% achieved INR reversal with first measured INR after PCC administration compared with 69% in the moderate-dose group (p<0.001). The median time to INR reversal was 6.9 hours in the low-dose PCC group and 1.9 hours in the moderate-dose PCC group (p=0.04). There were no differences between the groups in other secondary end points, including stabilization of TBI, days in the intensive care unit, total days of hospitalization, blood product administration, and adverse events.

CONCLUSIONS: Moderately dosed PCC at 35 IU/kg compared with a lower dosage of 25 IU/kg was associated with a higher percentage of INR reversal and more rapid time to INR normalization in patients with TBI. Future randomized controlled studies to further investigate this novel dose and the impact on potential reductions in the use of fresh frozen plasma are warranted.