Megaloblastic Anemia



  • Macrocytosis refers to a blood condition in which red blood cells (RBCs) are larger than normal. It is reported in terms of mean corpuscular volume (MCV). Normal MCV values range from 80 to 100 fL and vary by age and reference laboratory.
  • No complications arise from macrocytosis itself as an isolated finding; however, its presence can suggest an underlying pathologic state.
  • Macrocytosis with associated anemia (macrocytic anemia) can be broadly classified as megaloblastic or nonmegaloblastic anemia.
  • Megaloblastic anemia describes an anemic state characterized by the presence of abnormally large RBCs (macro-ovalocytes) and hypersegmented neutrophils in the peripheral blood and bone marrow.


  • The incidence and prevalence is unknown, although is significantly less common than iron deficiency anemia.
  • The most frequent causes of megaloblastic anemia are disorders resulting from vitamin B12 (cobalamin) or folate deficiency.


  • Megaloblastic anemia is a direct result of ineffective or dysplastic erythropoiesis caused by a defect in DNA synthesis that interferes with cellular proliferation and maturation.
  • When vitamin B12 or folate is deficient, RBC proliferation and maturation result in large erythroblasts with nuclear/cytoplasmic asynchrony. The erythroblasts become large, oval shaped, and contain a characteristic immature, lacy nucleus. These bone marrow features are called “megaloblastic.”
  • Nonmegaloblastic anemia are associated with accelerated erythropoiesis or increased red cell membrane phospholipid production.


  • The most common etiologies of megaloblastic anemia are vitamin B12 or folate deficiencies.
  • Medications or severe copper deficiencies are another less common cause of megaloblastic anemia.
  • Pernicious anemia
    • Common cause of megaloblastic anemia in adults but rare in children
    • A type of vitamin B12 deficiency anemia and is caused by a decrease in the secretion of intrinsic factor (IF) by gastric parietal cells in the setting of autoimmune atrophic gastritis. IF is a protein essential for absorption of vitamin B12 in the ileum.
  • Nonmegaloblastic macrocytic anemias can be due to
    • Alcohol intake
    • Liver disease (with normal vitamin B12 and folate),
    • Diamond-Blackfan anemia
    • Myelodysplastic syndrome

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