What should be ordered for a patient with macrocytosis?

Diagnostic Workup for a Patient with Macrocytosis (MCV 108)

For a patient with an MCV of 108, the provider should order a comprehensive evaluation including folate level, vitamin B12 level, reticulocyte count, peripheral blood smear, liver function tests, thyroid function tests, and assessment of alcohol use and medication history. 1, 2

Initial Diagnostic Tests

• Folate level: Folate deficiency is a common nutritional cause of macrocytosis when B12 levels are normal 2
• Vitamin B12 level: Even though the question mentions normal B12, confirming this is essential as B12 deficiency is a leading cause of macrocytosis 3
• Reticulocyte count: Critical for distinguishing between ineffective erythropoiesis (low/normal count) and increased red cell production from hemolysis or hemorrhage (elevated count) 1
• Peripheral blood smear: To evaluate for megaloblastic changes (macro-ovalocytes, hypersegmented neutrophils) or other morphologic abnormalities 4
• Liver function tests: Liver disease is a common cause of macrocytosis 5
• Thyroid function tests: Hypothyroidism can cause macrocytosis without anemia 2

Additional Considerations

• Medication review: Many medications can cause macrocytosis, particularly thiopurines (azathioprine, 6-mercaptopurine), anticonvulsants, and chemotherapeutic agents 1, 2
• Alcohol use assessment: Chronic alcohol consumption is a common cause of macrocytosis independent of nutritional deficiencies 4
• Hemolysis evaluation: If reticulocyte count is elevated, order haptoglobin, LDH, and bilirubin to assess for hemolysis 1
• Homocysteine and methylmalonic acid levels: These metabolic markers can help detect tissue B12 deficiency even when serum B12 levels appear normal 2, 6

When to Consider Bone Marrow Evaluation

• Persistent unexplained macrocytosis: If initial workup is negative 7
• Presence of other cytopenias: Particularly if anemia is present, as this increases diagnostic yield 7
• Suspected myelodysplastic syndrome or other primary bone marrow disorder: Especially in elderly patients with unexplained, persistent macrocytosis 8, 7

Management Based on Findings

• If folate deficiency is identified: Oral folic acid supplementation at 1 mg daily until blood counts normalize, then maintenance dose of 0.4 mg daily (0.8 mg for pregnant/lactating women) 9
• If B12 deficiency is identified: Initial treatment with 100 mcg IM daily for 6-7 days, followed by alternate day dosing for 7 doses, then every 3-4 days for 2-3 weeks, and finally monthly maintenance 10
• If medication-induced: Consider risk/benefit discussion with prescribing physician about medication adjustments 1
• If alcohol-related: Counsel on alcohol cessation and nutritional supplementation 4

Common Pitfalls to Avoid

• Missing mixed deficiencies: Iron deficiency can coexist with macrocytosis, resulting in a falsely normal MCV; check RDW and iron studies 1
• Assuming normal B12 levels rule out deficiency: Functional B12 deficiency can occur despite normal serum levels; consider methylmalonic acid and homocysteine testing in suspicious cases 6
• Neglecting follow-up: Even unexplained macrocytosis requires monitoring, as 11.6% of patients develop primary bone marrow disorders and 16.3% develop worsening cytopenias over time 7
• Overlooking medication effects: Always conduct a thorough medication review, as this is one of the most common causes of macrocytosis 1, 6