Anemia is one of the most commonly diagnosed conditions. It occurs when there are not enough healthy red blood cells to carry adequate oxygen to the body's cells and tissues. Macrocytic anemia is a special form of anemia. It is associated not only with lower amounts of healthy red blood cells but also causes unusually large red blood cells.

In 2010, more than 2.2 billion people worldwide were affected by anemia. The causes of macrocytic anemia are a bit more complicated than more common types.


Some studies suggest macrocytic anemias are present in two to four percent of patients. Older patients seem to be the most vulnerable to this type.

One study from Stanford showed that the cause of anemia was unknown in 35 percent of older patients, which is concerning because people are living longer and cases of macrocytic anemia are likely to increase in the elderly population.

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Megaloblastic Anemia

The most common type of macrocytic anemia is megaloblastic anemia. This form affects red blood cell development in the bone marrow, specifically the development of blast cells. Blast cells mature into various types of blood cells, including red blood cells.

In macrocytic anemia, a problem in the red blood cells' DNA prevents them from dividing. Instead, the cells grow into large megaloblasts with other abnormalities. Eventually, these megaloblasts crowd out the healthy blood cells, and the symptoms of anemia worsen.

Test tubes or bottles for blood, stethoscope and laboratory hematology analysis surrounded by text title of diagnosis of Megaloblastic Anemia lie in doctor workplace Shidlovski / Getty Images


Causes of Megaloblastic Anemia

The most common cause of megaloblastic anemia is a vitamin B12 deficiency. This deficiency develops from poor dietary intake or malabsorption and can also lead to a vitamin B9 or folate deficiency. It is rare except in the case of strict veganism or intestinal or stomach obstruction.

Symptoms of this type of macrocytic anemia can take up to 10 years to develop, primarily because the liver stores such a large amount of vitamin B12.

Doctor holds wooden cubes in his hands with text B12


Nonmegaloblastic Anemia

Another type of macrocytic anemia is nonmegaloblastic anemia. It occurs when a person has macrocytic anemia but does not have low vitamin B12 or folate.

In nonmegaloblastic anemia, the red blood cells are larger than normal, but they do not have the same structural abnormalities that appear in megaloblastic anemia.

Blood for vitamin B12 and folate test jarun011 / Getty Images


Causes of Nonmegaloblastic Anemia

Nonmegaloblastic anemia has many causes, including alcoholism, liver dysfunction, and hypothyroidism.

If doctors have ruled out these causes or cannot determine the cause of nonmegaloblastic anemia, it may be the result of myelodysplastic syndrome (MDS). MDS is a rare condition characterized by abnormal blood cell development in the bone marrow.

digital rendering of the body highlighting the liver


Other Causes

Macrocytic anemia can have many other causes as well. These include medications, like diuretics, chemotherapy, anticonvulsants, and antimicrobials. Antiretrovirals, specifically reverse transcriptase inhibitors used to treat HIV, can also cause macrocytic anemia.

Regular blood testing may be required when taking these medications to catch any potential side effects quickly.

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Symptoms of Macrocytic Anemia

Symptoms of macrocytic anemia may not develop until the condition is advanced. Symptoms vary depending on the cause and severity.

For example, megaloblastic anemia due to a vitamin B12 deficiency may cause shortness of breath, headache, fatigue, palpitations, and some neurological symptoms. Gastrointestinal symptoms, including loss of appetite and diarrhea, are also common in some forms of macrocytic anemia.

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Diagnosis of macrocytic anemia is done through blood testing, specifically a complete blood cell count and vitamin B12 and folate levels.

Other tests include a peripheral blood smear to assess the size and shape of the cells and a reticulocyte count to determine the number of developing red blood cells.

Test tube with blood sample for complete blood count (CBC) test jarun011 / Getty Images



Treatment for macrocytic anemia depends on the underlying cause. If low vitamin B12 or folic acid are the cause, doctors will typically recommend supplements and a diet rich in these nutrients. Supplements may also be helpful if the problem results from medication use. If excessive alcohol consumption is the cause, it usually resolves if the person stops drinking.

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Prognosis and Complications

If macrocytic anemia is caught and treated early, the prognosis is excellent. In rare cases, the person may not respond to therapy, in which case doctors may look for leukemia or myelodysplastic syndrome.

Neurological complications may arise from a vitamin B12 deficiency and and can be prolonged or permanent.

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