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Megaloblastic Anemia

Last Updated on Sep 09, 2015
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What is Megaloblastic Anemia?

Megaloblastic anemia is a type of anemia characterized by the formation of unusually large, abnormal and immature red blood cells called as megaloblasts by the bone marrow, which are released into the blood.


It is usually caused due to the deficiency of vitamin B12 and / or folate in the body as these two vitamins are the building blocks in the formation of healthy red blood cells.

What are the Causes of Megaloblastic Anemia?

The causes of megaloblastic anemia are as follows:

  • Deficiency of Cobalamin or Vitamin B12: Vitamin B12 is an essential requirement for the formation of red blood cells. It is absorbed from the diet by the digestive tract. It may become deficient in the body due to inadequate dietary intake or failure of the body to absorb the vitamin. The absorption of vitamin B12 is a complex process. The stomach secretes a substance called intrinsic factor which binds to the vitamin and takes it across the digestive tract in the intestine. Therefore, conditions affecting the stomach as well as the intestine can result in vitamin B12 deficiency. Stomach-related causes include total or partial surgical removal of stomach as in bariatric surgery, gastritis, gastric bypass surgery, and use of drugs such as proton pump inhibitors. Intestinal causes include Crohn’s disease, tropical sprue, worm infestation, HIV infection and pancreatitis. Megaloblastic anemia that arises due to lack of intrinsic factor is called pernicious anemia.
  • Deficiency of Folate: Folate may be deficient due to inadequate dietary intake or malabsorption. In addition, certain medications like methotrexate and trimethoprim affect folate metabolism. Drugs like phenytoin can prevent the absorption of folate. These can also precipitate megaloblastic anemia irrespective of adequate dietary intake. Patients with an alcoholism problem often suffer from folate deficiency.
  • Certain blood cancers such as acute myeloid leukemia and myelodysplasia are also associated with megaloblastic anemia.

What are the Symptoms and Signs of Megaloblastic Anemia?

The onset of megaloblastic anemia is extremely slow and it may decades for the symptoms to manifest themselves. Signs, symptoms and clinical features once manifested are plenty and are as follow:

  • Anemia: A decrease in the circulation of healthy red blood cells in the body causes anemia. The symptoms manifest as fatigue, pale skin, breathlessness, lightheadedness and fast heartbeat. Anemia could lead to infections of respiratory and urinary tracts

Other symptoms that may be noted in a patient of megaloblastic anemia include:

  • Loss of appetite, weight loss and diarrhea
  • Glossitis or inflammation of the tongue. The tongue appears bald
  • Jaundice
  • Nerve-related problems like numbness and tingling sensation, muscle weakness, difficulty in walking, and visual impairment
  • Insomnia, depression, panic attacks and memory loss
  • Infertility in both males and females
  • Folate deficiency during pregnancy can cause premature birth, fetal loss and nervous system defects.

How to Diagnose Megaloblastic Anemia?

Some diagnostic tests for megaloblastic anemia, and vitamin B12 and folate deficiency are as follows:

  • Peripheral Blood Smear: Examination of a peripheral blood smear show the presence of enlarged, irregular and abnormally shaped red blood cells.
  • Bone Marrow Biopsy: Enlarged and immature red blood cells are found in bone marrow and they confirm the diagnosis.
  • Serum Cobalamin: This is measured by ELISA (Enzyme Linked Immuno Sorbent Assay). Levels less than 100ng/L is diagnostic of a deficiency.
  • Serum Folate: This is also measured by ELISA technique.
  • Serum Methylmalonate and Homocysteine: In patients with cobalamin deficiency, serum methylmalonate and homocysteine levels are raised. This method is employed for early detection of cobalamin deficiency even in the absence of blood cell abnormalities.
  • Routine Blood Count: MCV or Mean Corpuscular Volume is raised in this disease, that is, the cell size is increased. Many symptomless patients are detected through the finding of a raised MCV on a routine blood count.

How to Treat Megaloblastic Anemia?

Treatment of megaloblastic anemia is tailored according to the underlying cause. Treating the specific deficiency of vitamins forms the mainstay.

  • Cobalamin Deficiency Treatment: Lifelong regular cobalamin injections are necessary for patients who have developed cobalamin deficiency. Hydroxycobalamin and cyanocobalamin are the most common forms used for the treatment. An underlying cause of cobalamin deficiency should be ruled out and, if present, should be treated. Oral medications are also available for treatment.
  • Folate Deficiency Treatment:Oral doses of 5-15 mg folic acid daily are sufficient. The duration of treatment depends on the underlying disease. It is usually necessary to treat for about 4 months. Patients who take anti-folate drugs are given folinic acid, a reduced form of folate.

How to Prevent Megaloblastic Anemia?

Dietary intake of both cobalamin and folic acid should be adequate. Foods that are rich in cobalamin are eggs, chicken, meat, milk, cheese and fish.

Foods that are rich in folic acid are green leafy vegetables, beans, peanuts, soybean, rice, barley, sprouts, oranges etc. Nowadays foods are fortified with folic acid to prevent brain and spinal cord related defects in babies. Foods that are fortified with folic acid include bread, enriched pasta, fortified rice etc.

Cobalamin as preventive treatment must be given to all patients who have had a total gastrectomy surgery done. It must also be given in patients who are on long-term proton pump inhibitor drug therapy.


  1. Harrison’s Textbook of Internal Medicine – 18th edition
  2. Nelson’s Textbook of Pediatrics
  3. Megaloblastic (Pernicious) Anemia in Children - (http://www.stanfordchildrens.org/en/topic/default?id=megaloblastic-pernicious-anemia-in-children-90-P02325)
  4. Anemia, Megaloblastic - (https://rarediseases.org/rare-diseases/anemia-megaloblastic/)

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