Subnormal Serum Folate and Macrocytosis Associated with Anticonvulsant Drug Therapy By FREDERICK A. Kin’sitn.

megaboblastic anemia occurring as a probable complication of anticon-vulsant drug therapy with hydantoin derivatives,1 more than 60 cases have now been described in the biterature.2’5 The clinical and hematologic aspects have been reviewed in detail elsewhere.25”’4 It is now well established that megaloblastic anemia may occur as a complication of the administration of diphenylhydantoin ( Dilantin, Phenytoin, Epanatin) either alone6’10”7 or in combination with other anticonvulsant 35797 18,21, 23,24,30,31,34,35 of Mysoline (primidone) alone4’16’19’25’29 and in combination with other drugs,4”2”320’2426 and of barbiturates alone.14’22’27”2’33 The development of megaboblastic anemia associated with anticonvubsant drug therapy is considered to be the result of folic acid deficiency. In the past, the presence of folic acid deficiency has been implied by the finding of a megaloblastic anemia in association with normal serum vitamin B12 con-centrations.2’4’5’14’17’25’32’4 More recently, direct evidence of folic acid de-ficiency has been obtained: subnormal values of serum fobate, measured b