Valproic acid is commonly used in the management of childhood
epilepsy. The known hematologic side effects of the
drug are
hemorrhagic diatheses,
thrombocytopenia, and hypofibrinogenemia. We studied coagulation parameters in 29 epileptic children receiving
valproic acid for at least 6 months. Their ages ranged between 2 and 18 years (10.2 +/- 4.9 years). The total
valproic acid dose was 250 to 1000 mg/day equivalent to 20 to 30 mg/kg/day.
Treatment duration ranged from 6 to 57 months. These children had not previously had a
hemostatic defect and had no family history of
bleeding disorders. Platelet count, prothrombin time, activated partial thromboplastin time, bleeding time,
fibrinogen, platelet aggregation assays, and
ristocetin cofactor activity levels were determined in all of the patients, but von Willebrand's factor
antigen levels could be determined in only 14 patients. The values of von Willebrand's factor
antigen ranged from 53 to 218% (104.1 +/- 42.3), and
ristocetin cofactor activity levels ranged from 11.5 to 218% (94.5 +/- 43.1). Six of the 29 children (20.7%) had decreased values of
ristocetin and cofactor activity and were considered to have acquired
von Willebrand's disease. The decreases in coagulation parameters were not dependent on either
valproic acid dose or
treatment duration. Two patients with low
ristocetin cofactor activity values had mild
epistaxis, which did not require discontinuation of
therapy. In patients receiving
valproic acid therapy, this side effect must be considered, especially before surgical intervention and serious traumatic conditions.