Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ DEFINITION ++ These anemias are caused by megaloblastic hematopoiesis that results from defective DNA synthesis. They most commonly result from folate or cobalamin (vitamin B12) deficiency. +++ ETIOLOGY AND PATHOGENESIS ++ Table 8–1 lists causes of megaloblastic anemia. By far the most common causes worldwide are folate deficiency and cobalamin deficiency. The 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) with exaggerated apoptosis of late precursors, which results in blood cytopenias. Mild hemolysis also occurs; the red cell life span is reduced by about 40%. ++Table Graphic Jump LocationTABLE 8–1CAUSES OF MEGALOBLASTIC ANEMIASView 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 Gastric reduction surgery 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, such as long-term exposure to weak folate antagonists (eg, trimethoprim or low-dose methotrexate) Inborn Errors Cobalamin deficiency Imerslund-Gräsbeck 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 N5-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 +++ 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. Folic acid deficiency and cobalamin deficiency have indistinguishable blood and marrow changes (megaloblastosis), but the former deficiency is not associated with neuropathology and the latter characteristically is (see “Pernicious Anemia” below). +++ LABORATORY FEATURES +++ Blood Cells ++ All cell lines are affected. In addition to anemia, leukopenia and thrombocytopenia are frequently present. Anemia is usually macrocytic, with a mean cell volume (MCV) of 100 to 150 fL or more, but coexisting iron deficiency, thalassemia trait, or inflammation may prevent macrocytosis. Erythrocytes show marked anisocytosis and poikilocytosis, with many oval macrocytes and, in severe ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.