Due to the smaller ratio between the cell's surface area and its volume, the capacity of erythrocytes to properly carry and transport hemoglobin is diminished.

Possible causes include folic acid and/or Vitamin B12 deficiencies, liver disease (including but not limited to results from chronic alcohol abuse), medications interfering with DNA synthesis (such as certain immunosuppressants like methotrexate and azathioprine), bone marrow disease, pregnancy, as well as autoimmune and endocrine conditions.

Due to the difference in the affected molecules, macrocytic anemia will vary in accordance with its underlying cause, with cases being divided into megaloblastic (megaloblastosis) and non-megaloblastic.

Some examples include impaired proprioception, paresthesia, loss of balance, poor memory, and peripheral neuropathy.

It mirrors a lot of standard anemia presentation in its hypoxemia-related symptoms: dizziness or fainting, fatigue, pale skin, shortness of breath, and fast or irregular heartbeat.

Two especially noteworthy physical symptoms of anemia are glossitis, the reddening of the tongue, and fingernails with a concave, "spoon-like" shape.

[2] In contrast, non-megaloblastic macrocytic anemias associated with a high reticulocyte count (reticulocytosis) may be caused by hemolysis or bleeding.

[2] For megaloblastic macrocytic anemias, useful tests may include serum levels of Vitamin B12, methylmalonic acid, and homocysteine.

[2] In countries that have not put such practices into place — including most European nations — folate deficiency remains a common cause of macrocytic anemia.