Effect of valproate on hemostatic function in patients with traumatic brain injury

Objectives: To evaluate whether valproate (VPA) resulted in laboratory or clinical evidence of a change in bleeding-related measures associated with VPA therapy in patients sustaining a traumatic brain injury. Methods: Fibrinogen, platelet count and clot elastic shear modulus using the Thrombelastograph® (TEG®) coagulation analyzer were measured at baseline, 4, 14, 30, and 180 days post-injury. Clinically significant events, defined as the trigger for requiring a transfusion, were identified and evaluated as to possible treatment effects. Results: Compared to baseline, the platelet count in the VPA groups was decreased on day 4, increased by 100% on day 14, and returned to baseline levels by day 30. Fibrinogen was significantly increased by day 4 and returned to baseline by day 30. The platelet count was correlated with an increase in the maximum amplitude or width of the TEG® tracing; a measure of strength of the clot, suggesting that valproate did not alter the clot strength contributed by platelets. None of the clinical events requiring transfusions appeared to be treatment related. Conclusions: No serious hemostatic adverse events occurred in the trauma patients receiving VPA or phenytoin that could be attributed to treatment.