effect of valproate monotherapy on hepatic and hemostatic functions in epileptic children: value of L-carnitine supplementation

ABSTRACT

The study included 15 epileptic children without previous hepatic or hemostatic defects [10 males and 5 females] aging 2 to 14 years selected from the outpatients attending the Pediatric Neurology Clinic of the Pediatric Department of Tanta University Hospital. We excluded patients receiving other medications which affect hepatic or platelet function, fifteen healthy children of matched age and sex served as controls. History, clinical examination and the following investigations were done for all of the cases EEG, complete blood count, total serum proteins, albumin, bilirubin, ammonia, and alanine aminotransferase [ALT]. Hemostatic studies included bleeding time [BT], clotting time [CT], prothrombin time [PT], activated partial thromhopiastin time [PTT], serum fibrinogen, protein C, von Willebrand factor antigen, platelet count and platelet aggregation. All of the hepatic and hemostatic parameters were done before, and 9 weeks after commencement of antiepileptic therapy with valproate [VPA]. Serum valproate level was measured after establishment of therapy and showed a good complience to treatment. L-carnitine was measured before and after valproate therapy then oral L-carnitine was supplemented in a dose of 100 mg/kg/day for two weeks in all of the studied cases. The studied hepatic and hemostatic function parameters mentioned above were repeated again after L-carnitine supplementation. Valproate therapy was associated with a significant decrease in serum L-carnitine with impairment of hepatic functions [manifested by a significant increase in serum bilirubin, ammonia and ALT]. Following oral administration of L-carnitine there was a significant decrease in serum bilirubin and ALT, Hemostatic disturbances were also observed after valproate therapy in the studied cases [manifested by a significant increase in BT, CT, PT and PTT, with a significant decrease in serum fibrinogen, serum protein C, platelet count and platelet aggregation], VPA therapy or L-carnitine administration did not significantly affect Von Willebrand factor. Most of the studied hemostatic parameters improved significantly in response to oral L-carnitine. None of our studied cases showed life threatening or Reye-like hepatotoxicity. We conclude that within the usual therapeutic serum levels of VPA, it could be associated with L-carnitine deficiency and hepatic synthetic dysfunction as well as decreased number and function of platelets. Most of these abnormalities could be reversed by co-administration of L-carnitine. The latter might be recommended in epileptic children on VPA therapy particularly those with abnormal liver or platelet functions and those at risk for hepatotoxicity