From the Guidelines
For macrocytosis without anemia and with normal liver enzymes, thyroid function, folate, and B12 levels, a comprehensive workup including a detailed medication review, alcohol history, and evaluation for hemolysis with reticulocyte count, haptoglobin, and LDH is recommended. The workup should focus on identifying other potential causes of macrocytosis, such as myelodysplastic syndromes, renal disease, or other underlying conditions 1.
Key Components of the Workup
- A detailed medication review to identify potential drugs causing macrocytosis, such as methotrexate, anticonvulsants, and certain chemotherapeutics
- A comprehensive alcohol history, as chronic alcohol use is a common cause of macrocytosis even with normal liver enzymes
- Evaluation for myelodysplastic syndromes with a peripheral blood smear and possibly bone marrow examination if clinically indicated, especially in older patients
- Assessment of kidney function, as renal disease can contribute to macrocytosis
- Evaluation for hemolysis with reticulocyte count, haptoglobin, and LDH, as suggested by the European Consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1
Additional Considerations
- In some cases, macrocytosis may be a normal variant, particularly in pregnancy or in certain families with hereditary macrocytosis
- If all investigations are negative and the patient remains asymptomatic with isolated macrocytosis, periodic monitoring of complete blood counts every 3-6 months is reasonable to detect any progression to anemia or other hematologic abnormalities
- The minimum workup should include complete blood count with MCV, reticulocytes, serum ferritin, transferrin saturation, and CRP, as outlined in the European Consensus 1
From the Research
Evaluation of Macrocytosis
- Macrocytosis is generally defined as a mean corpuscular volume greater than 100 fL 2
- The most common etiologies are alcoholism, vitamin B12 and folate deficiencies, and medications 2, 3
- History and physical examination, vitamin B12 level, reticulocyte count, and a peripheral smear are helpful in delineating the underlying cause of macrocytosis 2
Workup for Macrocytosis without Anemia
- Complete medical history, red cell parameters, and peripheral blood smear are simple, inexpensive tools which assist in identifying the underlying cause of macrocytosis 3
- Vitamin B12 and folate assays, thyroid function tests, and liver function tests may be performed to rule out common causes 3
- In the absence of anemia, macrocytosis may still be a clue to an underlying pathology, such as alcoholism or myelodysplastic syndrome 3
Role of Liver Enzymes and Thyroid Function
- Normal liver enzymes do not rule out liver disease as a cause of macrocytosis, as some liver conditions may not affect liver enzymes 4
- Hypothyroidism is a possible cause of macrocytosis, and thyroid function tests may be performed to evaluate this possibility 2
- Normal thyroid function and liver enzymes do not exclude other causes of macrocytosis, and further evaluation is still necessary 2, 3