What Is Macrocytic Anemia? Causes

• Impaired DNA production
  • Vitamin B12 (cobalamin) deficiency
  • Folate deficiency
  • Drugs
  • Antiretroviral therapies for human immunodeficiency virus infection (zidovudine)
  • Azathioprine or 6-mercaptopurine
  • Capecitabine
  • Cladribine
  • Cytosine arabinoside
  • Hydroxyurea
  • Imatinib and sunitinib
  • Methotrexate
• Shift to immature or red blood cells
  • Reticulocytosis (increase in the number of young red blood cells)
  • Action of erythropoietin (skips abnormally large red blood cells and stresses the production of excess red blood cells)
  • Aplastic anemia/Fanconi anemia (a condition in which the body stops producing new red blood cells)
  • Pure red cell aplasia (characterized by the absence of red blood cells precursor)
  • Primary bone marrow disorders
• Myelodysplastic syndrome (a group of disorders caused by impaired blood cell production)
  • Congenital dyserythropoietic anemia (inherited disorder that affects the development of red blood cells)
  • Sideroblastic anemia (a group of disorders characterized by an impaired ability of the bone marrow to produce normal cells)
  • Large granular lymphocyte leukemia (chronic blood cancer that affects white blood cells)
  • Lipid abnormalities (congenital disorders that involve hyperhomocysteinemia)
  • Liver disease
  • Hypothyroidism
• Idiopathic causes (causes of unknown origin)
  • Alcohol abuse
  • Multiple myeloma and other plasma cell disorders

Causes of macrocytosis include:

• Abnormal development of RBC: Impaired DNA production is the primary cause of abnormal RBC development. When the DNA synthesis is impaired, the cell cycle does not progress normally, leading to cell growth without division. Cell growth without division can lead to abnormally large red blood cell formation.
• Abnormal RBC membrane composition: Certain inherited and acquired medical conditions can disrupt the composition of the RBC membrane, resulting in increased cell size.
• Increased reticulocytes (young red blood cell count): In anemia, the signal from the hormone erythropoietin to increase RBC production may cause young RBCs to skip cell division, causing reticulocytes to enter the circulation. These reticulocytes appear larger and have an irregular shape.

Impaired RBC production is mainly caused by vitamin B12 deficiency and folic acid deficiency. 

Vitamin B12 deficiency causes

Vitamin B12 deficiency is common in vegetarians and vegans. Other causes include:

• Gastrointestinal abnormalities including pernicious anemia, gastritis, celiac disease, and inflammatory bowel disease
• Consequence of gastrointestinal surgeries such as gastrectomy, gastric bypass, and ileal resection
• Adverse reactions such as proton pump inhibitors and metformin or nitrous oxide abuse

Folic acid deficiency causes

Folic acid deficiency is commonly seen in older adults and people with alcoholism. Other causes include:

• Celiac disease
• Inflammatory bowel disease
• Small bowel resection
• Pregnancy
• Chronic hemolysis
• Drugs such as methotrexate, phenytoin, and trimethoprim