From the Guidelines
Macrocytic anemia, characterized by a low red blood cell count and high Mean Corpuscular Volume (MCV), is most commonly caused by vitamin B12 deficiency, folate deficiency, liver disease, alcoholism, certain medications, and myelodysplastic syndromes, and should be evaluated and treated promptly by a healthcare provider. The underlying causes of macrocytic anemia can be identified through a comprehensive evaluation, including a complete blood count (CBC), reticulocyte count, and tests for vitamin B12 and folate levels 1.
Common Causes of Macrocytic Anemia
- Vitamin B12 deficiency: can be treated with hydroxocobalamin 1 mg intramuscularly, administered on alternate days until there is no further improvement, then every 2 months 1
- Folate deficiency: can be treated with oral folic acid 5 mg daily for a minimum of 4 months, after excluding vitamin B12 deficiency 1
- Liver disease and alcoholism: require cessation of alcohol consumption and treatment of the underlying liver disease
- Certain medications: such as anticonvulsants, sulfasalazine, and methotrexate, may affect folic acid levels and require alternative treatments or dose adjustments
- Myelodysplastic syndromes: require referral to a hematologist for further evaluation and treatment
Evaluation and Treatment
The evaluation of macrocytic anemia should include a morphologic approach, characterizing the anemia based on the MCV, and a kinetic approach, focusing on the underlying mechanism of anemia 1. Treatment depends on the underlying cause, but often includes supplementation with vitamin B12 or folate, and dietary changes to include more B12-rich and folate-rich foods. Complete blood count follow-up testing is typically recommended after 1-2 months of treatment to monitor improvement.
From the Research
Causes of Anemia with Macrocytosis
- Macrocytic anemias are seen with vitamin B12 and folate deficiency, alcohol use, thyroid disease, hydroxyurea, antiretroviral drugs, myelodysplastic syndromes, and myeloma 2
- Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL) and can be caused by megaloblastic or nonmegaloblastic anemia 3
- Megaloblastic anemia is caused by deficiency or impaired utilization of vitamin B12 and/or folate, whereas nonmegaloblastic macrocytic anemia is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and by less commonly inherited disorders of DNA synthesis 3
Specific Causes
- Vitamin B12 and folate deficiency can lead to macrocytic anemia 2, 4, 3
- Alcohol use can cause macrocytic anemia 2, 3
- Thyroid disease can lead to macrocytic anemia 2, 3
- Myelodysplastic syndromes and myeloma can cause macrocytic anemia 2, 3
- Certain drugs, such as hydroxyurea and antiretroviral drugs, can lead to macrocytic anemia 2, 3
Diagnosis and Treatment
- Diagnosis of macrocytic anemia involves laboratory tests, including full blood count, iron studies, reticulocyte count, and blood test results 2, 4, 3
- Treatment of macrocytic anemia depends on the underlying cause and may involve vitamin B12 and folate supplementation, addressing underlying diseases or conditions, and discontinuing certain medications 2, 3