Abstract
Bleeding within the first 24 hours of life has been reported in some infants whose mothers received anticonvulsants. This study was designed to eveluate the relationship between Diphenylhydantoin (DPH) and coagulation defects. Eight cats were given DPH intraperitoneally daily (two cats received 2.5mg./kilo, two cats 5mg./kilo, four 10mg./kilo). These animals were followed weekly for coagulation abnormalities, neurologic toxicity and DPH blood levels. Cats receiving 10mg./kilo, for 5 to 15 days showed a decrease in Factors I, II, V, VII and X plus ataxia. Cats receiving 2.5 and 5.0mg./kilo showed a decrease in the same factors to a lesser degree. After one week of treatment with DPH, Factors I, II, V, VII and X were decreased 50% in all animals. Vitamin D dependent Factors II, VII and X returned to normal in cats on low doses of DPH. These Factors continued to fall in cats receiving 10mg./kilo. Animals on low dosage of DPH appeared to adapt and no longer showed a coagulation abnormality. Factor V fell initially and then rose above base line values in all cats after one week suggesting transient liver dys-function. Factor VIII remained normal in all the animals. To prove that the coagulation defect was dependent on Vit. K Three cats were treated with 10mg./kilo DPH and 1mg. Vit. K daily. This combination prevented the clotting abnormalities without preventing neurologic signs of DPH toxicity. Cord blood levels of DPH have been found increased over mother's DPH blood levels suggesting a mechanism for infant toxicity. Since this study in the cats shows the effect of DPH on the clotting factors reversible with Vit. K., prenatal treatment of mothers on DPH with Vit. K may be indicated.
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Hilgartner, M., Solomon, G., Kutt, H. et al. Diphenylhydantoin induced coagulation abnormalities. Pediatr Res 5, 408–409 (1971). https://doi.org/10.1203/00006450-197108000-00156
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DOI: https://doi.org/10.1203/00006450-197108000-00156