Evidence for folic acid deficiency in the genesis of anemic sickle cell crisis.

CUTELY DEPRESSED erythropoiesis in a decompensated hemolytic disorder such as sickle cell anemia results in a rapid fall in hematocrit which can be fatal if not promptly treated. Such intermittent inhibition of marrow activity has been previously reported in association with superimposed acute infection2123 and nutritional deficiency.hI More recently, the observation of megaloblastic maturation arrest coincident with so-called hemolytic crisis has aroused interest in the increased cellular demand for nucleic acid synthesis attending increased red cell turnover rates.’4”’ Both folic acid and vitamin B12 play essential roles in purine and pyrimidine nucleoprotein metabolism and the vast majority of megaloblastic anemias are relieved by one or the other agent.25 Previous reports cf maturation arrest occurring in hereditary spherccytosis26 and sickle cell anemia’3”4 have not shown definite pretreatment evidences of folic acid deficiency. Elevated urinary formiminoglutamic acid has been observed in recurrent crises of thalassemia major.24 In none of these instances, however, has there been hematobogic responsiveness to physiologic doses of vitamin B12, folic acid, or folinic acid. The present report concerns detailed observations in two patients with sickle cell anemia exhibiting biochemical evidence for folic acid deficiency. In one of these, there was a striking beneficial response to physiologic doses of oral folic acid both during an acute aregenerative crisis and again six and one-half honths after cessation of folic acid during a period of gradual fall in hematocrit. Five additional sickle cell patients tested had similar laboratory evidence of folic acid deficiency.