Anticonvulsivant-induced depression of clotting factors in children.

A few neonates born to mothers receiving anticonvulsant drugs during pregnancy have shown defects in vitamin K dependent clotting factors with or without clinical bleeding. Experimentally, phenytoin (diphenyl hydantoin, DPH) has induced clotting defects in cats and inhibited production of clotting factors in rat liver slices. Phenobarbital has produced similar but milder defects. Anticonvulsants have been observed to produce clotting defects in 9 children, 2 weeks to 8 years in age. Elevated levels of phenytoin or other anticonvulsants, or a combination of anticonvulsants were measured in the children. Six patients were on drug combination including two or more of the following: phenytoin, phenobarbital, primidone, carbamazepine, diazepam, ethosuximide. Clotting defects included: elevated prothrombin time, elevated partial thromboplastin time, diminished factors V, VII or X. All children had neurologic symptoms of anticonvulsant toxicity, but the only hematologic problems were oozing from venipuncture sites and increased bruising in 3. All patients were on normal diets and had normal liver function tests. By lowering the level of anticonvulsants, clotting factors returned toward normal. Elevated levels of anticonvulsants can potentially produce clotting defects in neonates and young children.