The megaloblastic anemias are a group of hypoproliferative disorders associated with a common characteristic morphology, an abnormal degree of ineffective erythropoiesis, and moderate hemolysis of circulating red cells. The underlying biochemical defect is impaired thymidylate formation, an essential rate-limiting preliminary step in the deoxyribuonucleic acid (DNA) synthesis of all body cells that requires tetrahydrofolic acid as a coenzyme. In a folate- and/or vitamin B12 deficient state, nuclear maturation and mitotic activity are delayed, although cytoplasmic development progresses normally. Cell division is decreased, and enlarged cells are produced with an increased cytoplasmic RNA-to-nuclear-DNA ratio. Hence, red cell precursors are retarded in formation, and intramedullary and extramedullary hemolysis ensues with the development of anemia. Although erythrocyte formation is most obviously impaired, dysplastic maturation of leukocytes and platelets also occurs, leading to leukopenia and thrombocytopenia in cases of severe disease.
KeywordsAplastic Anemia Pernicious Anemia Folate Deficiency Megaloblastic Anemia Tropical Sprue
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