Prolonged Prothrombin Time After Recombinant Activated Factor VII Therapy in Critically Bleeding Trauma Patients Is Associated With Adverse Outcomes

Background In trauma patients with significant hemorrhage, it is hypothesized that failure to normalize prothrombin time PT after recombinant activated factor VII rFVIIa treatment predicts poor clinical outcomes and potentially indicates a need for additional therapeutic interventions. Methods To assess the value of PT to predict outcomes after rFVIIa or placebo therapy, we performed a post hoc analysis of data from 169 severely injured, critically bleeding trauma patients who had 1-hour postdose PT measurements from two randomized clinical trials. Baseline characteristics and outcome parameters were compared between subjects with 1-hour postdose PT 18 seconds and PT 18 seconds. Results In rFVIIa-treated subjects, prolonged postdose PT values greater than or equal to 18 seconds were associated with significantly higher 24-hour mortality 60 vs. 3 p less than 0.001 and 30-day mortality, increased incidence of massive transfusion, and fewer intensive care unit-free days compared with postdose PT values less than 18 seconds. Recombinant rFVIIa-treated subjects with postdose PT greater than or equal to 18 seconds had significantly lower baseline hemoglobin levels, fibrinogen levels, and platelet counts than subjects with postdose PT values less than 18 seconds even though they received similar amounts of blood products before rFVIIa dosing. Placebo-treated subjects with postdose PT great than or equal to 18 seconds had significantly increased incidence of massive transfusion, significantly decreased intensive care unit-free days, and significantly lower levels of fibrinogen and platelets at baseline compared with subjects with postdose PT values greater than 18 seconds. The presence of prolonged PT after rFVIIa or placebo therapy was associated with poor clinical outcomes.