The result of a defect in either nuclear maturation or stimulated erythropoiesis.

True macrocytes represent a nuclear maturation defect associated with a deficiency of vitamin B12 or folate.

Macrocytes result from a disruption of mitotic division in the bone marrow.

Cells appear as mature, enlarged erythrocytes in the peripheral blood.

Macrocytes may also be caused by increased their output we stimulation which increases hemoglobin synthesis in developing cells resulting in premature release of particular sites into the circulating blood.

Such macrocytes due to premature release into the circulation appear macrocytic, basophilic and slightly hypo-chromic on smear.

Differential diagnosis:

DNA metabolism abnormalities-Folate deficiency, Vitamin B12 deficiency

Drugs including chemotherapy agents that affect or block DNA metabolism

Medications associated with elevated MCV include hydroxyurea, Methotrexate, trimethoprim, zidovudine, and 5-FU.

Lipid abnormalities- hypothyroidism, liver disease

Bone marrow disorders- myelodysplastic syndromes, large granular lymphocytic leukemia


Multiple myeloma


Fanconi anemia

In a study of outpatient blood counts involving 9527 patients, 3% had macrocytosis( Seppä).

The most common cause for macrocytosis was alcohol abuse.

In several other studies, vitamin B12 deficiency was the cause of macrocytosis in 5%-7% of patients.

In a study of 200 consecutive patients with MCVs over 100, the cause was established  in 80%: Sixteen of these patients had a low B12 level and 10 had a low folate level.

In recent years, folate has become an extremely unlikely cause of macrocytic anemias. 

In 1998, the Food and Drug Administration required folic acid fortification of enriched grain products in the United States to help decrease the risk of neural tube defects

Since 1998, anemia due to folate deficiency has essentially disappeared in individuals who have access to fortified grain products.

Folate deficiency is not the cause of anemia in any of the patients with low folate levels.

It is suggested folate analysis should be reduced or eliminated. 

Choosing Wisely campaign: Do not order red blood cell folate levels at all.


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