Continuing our series on anemia, lets now touch upon megaloblastic anemia, the second type of anemia most commonly seen due to a deficiency of Vitamin B12 or Folic acid, or both. Megaloblastosis involves large sized RBCs due to ineffective and delayed maturation of RBCs due to deficiency of essential Vitamin B12 and Folic acid.Vitamin B12 or methylcobalamin is an essential for DNA synthesis.

Causes Of Vitamin B12 Deficiency:

  • The commonest cause of Vitamin B12 deficiency is pure vegetarian, especially vegan diet. Vegetarian food has nil Vitamin B12. Milk and Milk products have very small quantities of Vitamin B12. Excluding these from diet is the commonest cause of megaloblastic anemia.
  • Fad diets including only juices or raw vegetables is another common cause of megaloblastic anemia.
  • Pernicious anemia or failure of Intrinsic Factor which is responsible for absorption of Vitamin B12. This is due to autoimmune destruction of gastric parietal cells. Anti acidity drugs like H2 receptor blockers can cause intrinsic factor failure.
  • Pancreatic diseases causing pancreatic insufficiency.
  • Disorders of terminal Ileum which is the part of small intestine where Vitamin B12 is absorbed, such as inflammatory bowel disease,tuberculosis etc.
  • Blind loop syndrome due to bacterial overgrowth.
  • Fish tapeworm infestation.
  • Some medications that can cause cobalamin deficiency includes purine analogs (6-mercaptopurine, 6-thioguanine, acyclovir), pyrimidine analogues (5-fluorouracil, 5-azacytidine, zidovudine), ribonucleotide reductase inhibitors (hydroxyurea, cytarabine arabinoside), and drugs that affect cobalamin metabolism (p -aminosalicylic acid, phenformin, metformin).
  • Folic acid deficiency is most commonly due to unhealthy diet fads.

Signs And Symptoms Of Megaloblastic Anemia

  • In mild anemia, the patient may have no symptoms.
  • Gastrointestinal symptoms such as loss of appetite, weight loss, nausea, and constipation may be seen in some.
  • Some patients may have a sore tongue and canker sores.
  • Neurological changes including psychiatric changes, peripheral neuropathy can be seen in both Vitamin B12 and folic acid deficiency
  • Severe B12 deficiency can cause a spinal cord degeneration called Subacute combined degeneration of cord which causes sensory loss, imbalance, etc.
  • Relevant history pointing to cause of deficiency should be taken.


  • Initial workup for megaloblastic anemia should include a complete blood count (CBC), RBC indices, peripheral smear, reticulocyte count, lactate dehydrogenase (LDH), indirect bilirubin, iron and ferritin assays, serum cobalamin and serum folate, and possibly an RBC folate evaluation.
  • PS morphology reveals large immature RBCs as well as hypersegmented neutrophils.
  • Serum Vitamin B12 levels¬† (cobalamin)¬† Reference range: 200-900 pg/mL.
  • Serum folate reference range: 2.5-20 ng/mL.
  • In past, Schillings test was used for Pernicious anemia.
  • Bone marrow aspiration studies can be done.


*Most patients are treated with cobalamin or folate. Since megaloblastic anemias usually develop gradually, many patients adjust to low hemoglobin levels and do not require transfusions.
*There are several forms of cyanocobalamin available for treatment of B-12 deficiencies. Only intramuscular and oral cyanocobalamin are recommended. The effectiveness of oral cyanocobalamin in managing cobalamin-related neurological disorders has not been proven. Hence, oral cyanocobalamin is not recommended for cobalamin-related neurological disorders.
*Folic acid supplementation is given in oral form.




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