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Megaloblastic Anemia

Megaloblastic Anemia
portrait of José Antonio Zumalacárregui Ph.D.
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José Antonio Zumalacárregui Ph.D.
Medically reviewed by our Medical staff

Last update: 18-08-2021

How else can it be called?

  • Folic acid deficiency anemia

  • Vitamin B12 deficiency anemia

  • ICD-10: D53.1

What is megaloblastic anemia?

Megaloblastic anemia is a type of macrocytic anemia in which the bone marrow produces immature red blood cells. This condition results from the inhibition of DNA synthesis during the production of red blood cells (RBCs).

Anemia refers to a decrease amount of hemoglobin in the blood. Hemoglobin is an essential component of red blood cells, whose deficit prevents the correct supply of oxygen to cells and tissues of the body.

Megaloblastic anemia is considered a type of macrocytic anemia because the size of red blood cells present in the blood is larger than normal. It is called macrocytic anemia when the Mean Corpuscular Volume (MCV) is greater than 100 femtoliters (MCV>100 fl). It means that red blood cells are unusually large and structurally abnormal.

In this type of anemia, there is an excess of megaloblasts. Megaloblasts are large, abnormally developed and dysfunctional red blood cells.

The production of megaloblasts is the result of impaired DNA synthesis. As a consequence, the bone marrow produces megaloblasts instead of producing functional red blood cells, usually due to deficiency of certain vitamins.

What causes megaloblastic anemia?

The most common causes of megaloblastic anemia are:

  • Vitamin B12 (cobalamin) deficiency:
  • Vitamin B9 (folic acid/folate) deficiency:
    • Poor dietary intake
    • Alcoholism
    • Malabsorption
    • Increased consumption: In pregnancy and in growth stages, there is a greater need of folic acid
    • Exfoliative dermatitis and psoriasis
    • Tropical sprue
    • Drug interference: Many drugs can interfere the adequate synthesis of DNA such as antineoplastic drugs, folate antagonists, antiepileptic drugs, etc.
  • Congenital disorders (present at birth)
  • Lesch Nyhan syndrome
  • Orotic aciduria
  • Thiamine-responsive megaloblastic anemia syndrome

The liver stores vitamins B9 and B12. These vitamins take part in the synthesis of red blood cells.

Megaloblastic anemia represents from 2% to 5% of all total anemias.

What are the main symptoms of megaloblastic anemia?

The most common symptoms of megaloblastic anemia are:

  • Jaundice (yellowing of the skin)
  • Pallor (pale skin)
  • Fatigue, weakness, and dizziness
  • Mood swings and irritability
  • Glossitis (inflammation and pain of the tongue)
  • Diarrhea, abdominal pain, and indigestion
  • Nausea and vomiting
  • Paresthesia (tingling and numbness in the legs and arms)

How can it be detected?

A blood test is the main diagnostic tool since it shows macrocytic anemia.

Anemia means low levels of hemoglobin in the blood (less than 13 g/dl in men, 12 mg/dl in women, and 11 g/dl in pregnant women) while macrocytic means increased Mean Corpuscular Volume (MCV>100 fl).

Specific tests can also confirm vitamin B12 and folic acid deficiency as the cause of this type of anemia:

  • The normal range of vitamin B12 in the blood is from 200 to 900 pg/ml
  • The normal range of folic acid or vitamin B9 in the blood is from 3 to 17 ng/ml

In addition, other blood disorders may be present:

  • Increased lactate dehydrogenase (DHL)
  • Slight increase in indirect (unconjugated) bilirubin
  • Elevated homocysteine
  • Low levels of haptoglobin

What is the recommended treatment?

The treatment depends on the underlying causes that are producing deficiencies of vitamin B12, folic acid or both simultaneously.

As a general rule:

  • If there is a deficiency of vitamin B12, it can be treated with cyanocobalamin or hydroxocobalamin, usually through intramuscular injections (IM).
  • If there is a deficiency of folic acid (vitamin B9), administration of folic acid is necessary. It should be closely monitored, since the condition may worsen if there is also a vitamin B12 deficiency and only folic acid is being administered.
Medically reviewed by our Medical staff on 18-08-2021


  • Harrison’s Hematology and Oncology (3rd Ed) 2017, Dan L. Longo, ISBN: 978-1-25-983582-7, Pag. 96.
  • First Aid for the Basic Sciences: Organ Systems (3rd Ed) 2017, Tao Le, William L. Hwang, Vinayak Muralidhar, Jared A. White and M. Scott Moore, ISBN: 978-1-25-958704-7, Pag. 277.
  • Encyclopedia of Human Nutrition (2nd Ed) 2005, J M Scott and P Browne, ISBN 0-12-150110-8, Vol. I Pag. 109.
  • Robbins Basic Pathology (10th Ed) 2018, Vinay Kumar, Abul K. Abbas, Jon C. Aster, ISBN: 978-0-323-35317-5, Pag. 456.

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