Coagulation disorders with valproic acid in children
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Coagulation disorders with valproic acid in children The use of valproic acid appears to be associated with a high incidence of coagulation disorders in children with seizures or epilepsy, according to results of a longitudinal study. In this prospective trial, 23 such patients who were newly treated with valproic acid were assessed. Blood samples were taken before treatment start, after less than 6 weeks of treatment, after 6 weeks to 6 months of therapy, then after greater than 6 months of treatment. Furthermore, 35 neurologically healthy children not receiving any drugs were included as a control group. During the study, there were no clinical signs of bleeding or apparent signs of a coagulation disorder, and no patients developed haemorrhage. Valproic acidinduced thrombocytopenia occurred in 8.7% of patients; there were no patients with severe thrombocytopenia. Thrombelastography testing showed 47% of valproic acid recipients had altered platelet function. Valproic acid was also associated with a significant reduction in prothrombin time, and a significant increase in activated partial thromboplastin time. Valproic acid was associated with a significant decrease in antiprotease antithrombin III, and in the activity of von Willebrand factor antigen and von Willebrand factor ristocetin cofactor. There was a decrease in factor XIII activity associated with the use of valproic acid for greater than 6 months. Fibrinogen was also significantly reduced in valproic acid recipients; 57.2% of patients developed fibrinogen deficiency of < 150 mg/dL. Of note, there was a significant positive correlation between the clotting times of epinephrine and adenosindiphosphate, and valproic acid serum concentration; this was an indication of a dosedependent platelet function disorder. The authors concluded that there is a high frequency of "different, subclinical valproate-induced coagulation abnormalities". Koenig S, et al. High incidence of vaproate-induced coagulation disorders in children receiving valproic acid: a prospective study. Blood Coagulation and 801118440 Fibrinolysis 19: 375-382, No. 5, Jul 2008
0114-9954/10/1216-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved
Reactions 23 Aug 2008 No. 1216
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