What causes macrocytic anemia?

From the Guidelines

Macrocytic anemia is primarily caused by vitamin B12 and folate deficiency, which are the most common causes of megaloblastic, macrocytic anemia. The causes of macrocytic anemia can be broken down into several key categories, including:

• Vitamin B12 deficiency, which can result from inadequate dietary intake, pernicious anemia, or malabsorption 1
• Folic acid deficiency, which may indicate non-adherence with daily multivitamin and mineral supplements or malabsorption, and can also be affected by certain medications such as anticonvulsants, sulfasalazine, and methotrexate 1
• Other causes, such as alcoholism, liver disease, and certain medications like methotrexate, phenytoin, and chemotherapy drugs, which can lead to macrocytosis through various mechanisms, including direct toxic effects on bone marrow and interference with folate metabolism It is essential to identify and address the underlying cause of macrocytic anemia, as treatment typically involves targeting the specific deficiency or condition, such as vitamin supplementation for deficiencies or alcohol cessation for alcoholism-related cases 1. In cases of vitamin B12 deficiency, treatment with hydroxocobalamin 1 mg intramuscularly is recommended, with the frequency of administration depending on the presence of neurological involvement and the severity of the deficiency 1. For folic acid deficiency, oral folic acid 5 mg daily is recommended for a minimum of 4 months, after excluding vitamin B12 deficiency 1.

From the Research

Causes of Macrocytic Anemia

• Megaloblastic anemia, which is caused by deficiency or impaired utilization of vitamin B12 and/or folate 2, 3, 4, 5
• Nonmegaloblastic macrocytic anemia, which can be caused by various diseases such as:
  • Myelodysplastic syndrome (MDS) 2, 3
  • Liver dysfunction 2, 3, 6
  • Alcoholism 2, 3, 6
  • Hypothyroidism 2, 3, 6
  • Certain drugs 2
  • Inherited disorders of DNA synthesis 2
  • Chronic liver dysfunction 3
  • Myelodysplastic disorders 3
  • Release of reticulocytes in the normal physiologic response to acute anemia 3

Specific Causes of Megaloblastic Anemia

• Vitamin B12 deficiency, which can be caused by pernicious anemia or other conditions 4, 5
• Folate deficiency 3, 5
• Impaired DNA synthesis 3

Diagnosis and Testing

• Blood smear to differentiate between megaloblastic and nonmegaloblastic anemia 6
• Vitamin B12 and red blood cell folate levels 6
• Reticulocyte count 6
• Thyroid and liver function tests 6
• Schilling test to determine if B12 can be absorbed 6