What Is the Most Common Cause of Macrocytic Anemia?

Medically Reviewed on 1/6/2022
macrocytic anemia
The most common causes of macrocytic anemia include vitamin B12 deficiency and folate deficiency.

Macrocytic anemia is a kind of anemia in which the erythrocytes (red blood cells) are abnormally big, a condition called macrocytosis or macrocythemia. The size of these red blood cells (RBCs) makes them more likely to rupture prematurely.

However, like with all types of anemia, macrocytic anemia has:

  • Low hemoglobin levels (due to increased RBC destruction)
  • A low number of normal red blood cells, which are mature cells with good functionality and are of smaller size

Macrocytic anemia is a condition that usually does not appear on its own but is caused by an underlying condition.

The most common causes of macrocytic anemia include:

  • Vitamin B12 deficiency
  • Folate deficiency

Even though the patient takes adequate vitamins through diet, they may not be absorbed well by the intestines due to certain conditions, such as:

Folate deficiency is a common condition in pregnancy that leads to severe anemia. Recent studies showed that the incidence of macrocytic anemia is higher than initially believed.

Other conditions that cause macrocytic anemia include:

A minor degree of macrocytosis (mean corpuscular volume rarely greater than 110 fL) may be noticed after:

  • Recent hemorrhage (more than one week)
  • Hemolytic anemia (anemia caused by rapid death of RBCs)

16 symptoms of macrocytic anemia

The patient may have general symptoms that are typical for anemia, which range from mild to severe and includes:

  1. Fatigue
  2. Diarrhea
  3. Pallor
  4. Dizziness
  5. Breathing issues
  6. Rapid heartbeat
  7. Poor concentration
  8. Loss of balance
  9. Loss of appetite
  10. Weight loss
  11. Numbness and tingling in the arms and legs
  12. Confusion
  13. Memory loss
  14. Depression
  15. Mouth ulcers
  16. Hair loss

It is recommended to consult the doctor if a person experiences any serious symptoms, especially increased heart rate, breathing problems, and neurological issues.

What are the different types of macrocytic anemia?

Macrocytic anemia is categorized into two main types:

  1. Megaloblastic macrocytic anemia:
    • Megaloblastic anemia is the most common type of macrocytic anemia, which is caused when the bone marrow produces structurally abnormal and immature megaloblasts.
      • Megaloblasts are large red blood cells that are produced due to errors in DNA synthesis.
      • Megaloblasts usually die within the bone marrow.
    • Megaloblastic anemia is caused by the deficiency of:
      • Vitamin B12
      • Folate
      • Drugs, such as:
        • Anticancer
        • Antiretroviral
        • Antiseizure
  2. Nonmegaloblastic macrocytic anemia:
    • Non-megaloblastic anemia is not caused by an abnormality in the DNA synthesis, but it is caused due to metabolic abnormalities and liver diseases. 
      • It is believed that the size of red blood cells (RBCs) is increased because of high cholesterol and lipids in the RBCs cell membrane.
    • Non-megaloblastic anemia is caused by:


Sickle cell disease is named after a farming tool. See Answer

How to diagnose macrocytic anemia

Macrocytic anemia is mostly asymptomatic, and the condition is typically diagnosed during routine blood work.

If the patient presents with symptoms of anemia, the doctor takes a thorough medical history. The doctor especially asks questions about diet and other medical conditions.

Blood tests

  • If the complete blood count test indicates the presence of anemia and large red blood cells (RBCs), the doctor may prescribe a peripheral blood smear
  • Blood tests to measure:
  • Macrocytic anemia may be caused by underlying diseases, so various blood tests are done to check for:
    • Liver diseases
    • Thyroid function
    • Levels of vitamin B12 and folate

Peripheral blood smear

A small smear of blood is taken on a slide and is studied under the microscope. This test shows the early macrocytic changes of the red blood cells.

If the diagnosis is unclear, the doctor may advise bone marrow biopsy to make an appropriate diagnosis.

What are the treatment options for macrocytic anemia?

Treatment for macrocytic anemia is achieved by treating the underlying cause.

The initial treatment should be replenishing the nutritional deficiencies in the body. To achieve this, one must increase their intake of foods rich in vitamin B12 and folate and take supplements, such as:

  • Red meat (especially liver)
  • Chicken
  • Eggs
  • Fish
  • Lentils
  • Green vegetables
  • Fortified grains

The treatment regimen may vary with different types of macrocytic anemia.

Megaloblastic macrocytic anemia treatment

Non-megaloblastic microcytic anemia treatment

Provide treatment for the underlying causes, such as:

If the underlying cause of anemia is severe, one may require a blood transfusion.

Preventive (prophylactic) folate supplementation may be advised for patients with higher-than-normal folate requirements, such as pregnant women or those on drugs known to cause anemia.

Medically Reviewed on 1/6/2022
Image Source: iStock Images

Braunstein EM. Megaloblastic Macrocytic Anemias. MSD Manuals. https://www.msdmanuals.com/en-in/professional/hematology-and-oncology/anemias-caused-by-deficient-erythropoiesis/megaloblastic-macrocytic-anemias

National Organization for Rare Disorders. Anemia, Megaloblastic. https://rarediseases.org/rare-diseases/anemia-megaloblastic/

Nagao T, Hirokawa M. Diagnosis and treatment of macrocytic anemias in adults. J Gen Fam Med. 2017;18(5):200-204. Published 2017 Apr 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689413/