Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android. Learn more here!


  • These disorders are caused by impaired synthesis of DNA.

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

  • 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 with hypersegmented neutrophils in the marrow and blood. Megakaryocytes may be abnormally large with nuclear abnormalities.


  • 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.

  • The condition 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 latter characteristically is (see “Pernicious Anemia” below).

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.