Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content ++ DEFINITION ++ Disorders caused by impaired synthesis of DNA. Prototype is pernicious anemia, a deficiency of vitamin B12 (cobalamin) caused by lack of intrinsic factor, required for its absorption. Characteristics are megaloblastic cells, typically present in the erythroid series as large cells with immature-appearing nuclei but with increasing hemoglobinization of the cytoplasm—often referred to as nuclear-cytoplasmic asynchrony. Megaloblastic granulocytic cells have large size, giant band neutrophils are a feature in the marrow and hypersegmented neutrophils in the marrow and blood. Megakaryocytes may be abnormally large with nuclear abnormalities. Other rapidly dividing tissue cells, such as intestinal epithelium and uterine cervical epithelium may also show cytologic abnormalities. A uterine cervical smear when megaloblastic cytopoiesis is present may be strikingly dysplastic. ++ ETIOLOGY AND PATHOGENESIS ++ Table 8–1 lists causes of megaloblastic anemia. Underlying defect is impaired DNA synthesis because of failure of conversion of dUMP to dTMP. Intramedullary destruction of red cell precursors (ineffective erythropoiesis) is a major feature of megaloblastic anemia. Ineffective granulopoiesis and thrombopoiesis are also present and can result in neutropenia and thrombocytopenia. Ineffective hematopoiesis is characterized by marked hyperplasia of precursor cells (hypercellular marrow) but exaggerated apoptosis of late precursors, which results in blood cytopenias. Mild hemolysis also occurs; the red cell life span is reduced by about 40 percent. ++Table Graphic Jump LocationTABLE 8–1CAUSES OF MEGALOBLASTIC ANEMIASView Table|Favorite Table|Download (.pdf) TABLE 8–1 CAUSES OF MEGALOBLASTIC ANEMIAS Folate Deficiency Decreased intake Poor nutrition Old age, poverty, alcoholism Hyperalimentation Hemodialysis Premature infants Spinal cord injury Children on synthetic diets Goat's milk anemia Impaired absorption Nontropical sprue Tropical sprue Other disease of the small intestine Increased requirements Pregnancy Increased cell turnover Chronic hemolytic anemia Exfoliative dermatitis Cobalamin Deficiency Impaired absorption Gastric causes Pernicious anemia Gastrectomy Zollinger-Ellison syndrome Intestinal causes Ileal resection or disease Blind loop syndrome Fish tapeworm Pancreatic insufficiency Decreased intake Vegans Acute Megaloblastic Anemia Nitrous oxide exposure Severe illness with Extensive transfusion Dialysis Total parenteral nutrition Drugs Dihydrofolate reductase inhibitors Antimetabolites Inhibitors of deoxynucleotide synthesis Anticonvulsants Oral contraceptives Others Inborn errors Cobalamin deficiency Imerslund-Graesbeck disease Congenital deficiency of intrinsic factor Transcobalamin deficiency Errors of cobalamin metabolism "Cobalamin mutant" syndromes with homocystinuria and/or methylmalonic acidemia Errors of folate metabolism Congenital folate malabsorption Dihydrofolate reductase deficiency N 5-methyl FH4 homocysteine-methyltransferase deficiency Other errors Hereditary orotic aciduria Lesch-Nyhan syndrome Thiamine-responsive megaloblastic anemia Unexplained Congenital dyserythropoietic anemia Refractory megaloblastic anemia Erythroleukemia Source: Williams Hematology, 8th ed, Chap. 41, Table 41–5, p. 545. ++ CLINICAL FEATURES ++ Anemia develops gradually and patients can adapt to very low hemoglobin levels. Eventually, as it progresses, the presenting symptoms are those of anemia with weakness, palpitation, fatigue, light-headedness, and shortness of breath. May present initially with neurologic manifestations without anemia. Folic acid deficiency and cobalamin deficiency have indistinguishable blood and marrow changes (megaloblastosis), but the former deficiency is not associated with neuropathology and the ... GET ACCESS TO THIS RESOURCE Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth Get Free Access Through Your Institution Contact your institution's library to ask if they subscribe to McGraw-Hill Medical Products. What is MyAccess? Create a FREE MyAccess profile to: Use this site remotely Bookmark your favorite content Track your self-assessment progress and more!