From the Guidelines
Macrocytosis with normal Vitamin B12 and folate levels is most likely caused by myelodysplastic syndrome, alcohol use disorder, liver disease, medications, hypothyroidism, or reticulocytosis from hemolysis or blood loss, and requires further investigation to determine the underlying cause. According to the study by 1, macrocytic anemia with normal or low reticulocytes can be caused by myelodysplastic syndrome, vitamin B12 deficiency, folate deficiency, long-term cytostatic medication, hypothyroidism, alcoholism, or thiamine-responsive megaloblastic anemia syndrome. However, since vitamin B12 and folate levels are normal in this case, the focus should be on other potential causes.
Some key points to consider in the investigation of macrocytosis with normal B12 and folate levels include:
- A thorough history and physical examination to identify potential causes such as alcohol use disorder, liver disease, or hypothyroidism
- Additional laboratory tests, including:
- Liver function tests to evaluate for liver disease
- Thyroid function tests to evaluate for hypothyroidism
- Reticulocyte count to evaluate for reticulocytosis
- Peripheral blood smear to evaluate for abnormalities in red blood cell morphology
- Hemolysis markers, such as LDH and haptoglobin, to evaluate for hemolysis
- If initial investigations are inconclusive, bone marrow examination may be necessary to rule out myelodysplastic syndrome or other hematologic disorders, as suggested by 1.
Management of macrocytosis with normal B12 and folate levels depends on treating the underlying cause, such as:
- Alcohol cessation for alcohol use disorder
- Medication adjustment for medications that may be causing macrocytosis
- Thyroid hormone replacement for hypothyroidism
- Treatment of underlying liver disease or other conditions that may be contributing to macrocytosis. The mean corpuscular volume (MCV) should be monitored periodically to assess response to interventions, with the frequency depending on the identified cause and clinical context.
From the FDA Drug Label
While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy The cause of macrocytosis with normal Vitamin B12 and normal folate levels is not directly stated in the drug label.
- Key points:
- Macrocytosis has occurred in patients taking phenytoin.
- It usually responds to folic acid therapy, but this does not explain the cause of macrocytosis with normal folate levels. 2
From the Research
Causes of Macrocytosis with Normal Vitamin B12 and Normal Folate Levels
- Macrocytosis can be caused by various factors, including alcoholism, liver disease, hypothyroidism, primary bone marrow dysplasias, and certain medications 3
- A study found that alcoholism was the etiological factor in 36.5% of cases, while liver disease and myelodysplastic syndrome were also identified as causes of macrocytosis 4
- Liver disease, particularly alcoholic liver cirrhosis, can lead to macrocytosis, even with normal folate levels 5
- Other causes of macrocytosis with normal Vitamin B12 and folate levels include:
- A careful medical history, physical examination, and laboratory tests, including peripheral smear and reticulocyte count, can help identify the underlying cause of macrocytosis 3, 4, 6