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Anticonvulsivant-induced depression of clotting factors in children
Insights
Anticonvulsant drugs during pregnancy can cause vitamin K-dependent clotting factor defects in newborns. Lowering anticonvulsant levels in children restored clotting factors toward normal.
Area of Science:
- Pharmacology
- Hematology
- Pediatrics
Background:
- Anticonvulsant medications are frequently prescribed during pregnancy.
- Neonates born to mothers on anticonvulsants may exhibit vitamin K-dependent clotting factor abnormalities.
- Previous studies indicated phenytoin (diphenyl hydantoin, DPH) and phenobarbital can induce clotting defects.
Purpose of the Study:
- To investigate the relationship between anticonvulsant drug levels and clotting factor defects in children.
- To identify specific clotting factor abnormalities associated with anticonvulsant toxicity.
- To determine if reducing anticonvulsant levels improves clotting function.
Main Methods:
- Observational study of 9 children (2 weeks to 8 years) with suspected anticonvulsant-induced clotting defects.
- Measurement of anticonvulsant drug levels (phenytoin, phenobarbital, carbamazepine, diazepam, ethosuximide, primidone).
- Assessment of clotting parameters including prothrombin time, partial thromboplastin time, and specific clotting factors (V, VII, X).
Main Results:
- Elevated anticonvulsant levels were detected in children with clotting defects.
- Observed defects included prolonged prothrombin time, prolonged partial thromboplastin time, and reduced factors V, VII, or X.
- Neurologic symptoms of toxicity were present in all children; mild hematologic issues (bruising, bleeding) in 3.
- Clotting factors normalized upon reduction of anticonvulsant drug levels.
Conclusions:
- Elevated anticonvulsant levels can cause significant clotting factor defects in neonates and young children.
- These defects are potentially reversible by adjusting medication dosages.
- Monitoring clotting function in children on anticonvulsants is crucial, especially with elevated drug levels.
Abstract:
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.