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  • These anemias are caused by megaloblastic hematopoiesis that results from defective DNA synthesis.

  • They most commonly result from folate or cobalamin (vitamin B12) deficiency.


  • 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%.



  • 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).


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 ...

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