What further tests are recommended for a 70-year-old male with macrocytosis and normal hemoglobin levels?

Diagnostic Workup for Macrocytosis in a 70-Year-Old Male with Normal Hemoglobin

For a 70-year-old male with isolated macrocytosis (MCV 102) and normal hemoglobin (152), the most appropriate next step is to order vitamin B12, folate, TSH, liver function tests, and reticulocyte count to determine the underlying cause.

Initial Assessment of Macrocytosis

The patient presents with:

• Hemoglobin: 152 (normal)
• MCV: 102 (elevated, indicating macrocytosis)
• RBC count: 4.44 (normal)
• MCH: 34.2 (slightly elevated)
• Other CBC components: normal

This represents isolated macrocytosis without anemia, which requires systematic evaluation to identify the underlying cause.

Diagnostic Algorithm for Macrocytosis

Step 1: Essential Laboratory Tests

• Vitamin B12 and folate levels - Critical first-line tests as deficiencies are common causes of macrocytosis, especially in elderly patients 1, 2
• Reticulocyte count - Helps differentiate between ineffective erythropoiesis and increased RBC production 3
• Peripheral blood smear - To assess for macro-ovalocytes and hypersegmented neutrophils (suggesting megaloblastic anemia) 2
• Liver function tests - Liver disease is a common cause of macrocytosis 4, 5
• TSH - Hypothyroidism can cause macrocytosis 2

Step 2: Additional Testing Based on Clinical Suspicion

• Serum homocysteine and methylmalonic acid - More sensitive markers for vitamin B12 deficiency, especially with borderline B12 levels 6
• Alcohol use assessment - Alcohol is one of the most common causes of macrocytosis 4, 5
• Medication review - Certain medications (e.g., anticonvulsants, chemotherapeutics, methotrexate) can cause macrocytosis 2

Common Causes of Macrocytosis to Consider

1. Vitamin B12 or folate deficiency - Most common nutritional causes 2, 4

   • Vitamin B12 deficiency requires prompt diagnosis as it can lead to permanent neurological damage if untreated for >3 months 7

2. Alcohol use - A leading cause of macrocytosis even without liver disease 4, 5

   • MCV >100 fL in patients with liver disease strongly suggests alcohol-related etiology 5

3. Medications - Various drugs can cause macrocytosis 6

   • Anticonvulsants, chemotherapeutics, antiretrovirals

4. Liver disease - Both alcoholic and non-alcoholic liver disease can cause macrocytosis 5

5. Hypothyroidism - Can present with macrocytosis 2

6. Myelodysplastic syndromes - Should be considered in elderly patients 6

   • May require bone marrow evaluation if other causes are ruled out

Important Considerations and Pitfalls

• Don't overlook vitamin B12 deficiency - Even with normal hemoglobin, B12 deficiency can cause neurological damage if left untreated 7

• Consider mixed deficiencies - Multiple nutritional deficiencies can coexist, and one may mask the other 3

• Avoid premature bone marrow evaluation - First exhaust non-invasive testing for common causes 1

• MCV >100 fL with normal hemoglobin - Often indicates early deficiency states or compensated hemolysis 6

• Age-related considerations - In elderly patients, macrocytosis may be the earliest sign of myelodysplastic syndrome 6

When to Consider Bone Marrow Evaluation

Bone marrow aspiration/biopsy should be considered if:

• Initial workup is negative
• Persistent unexplained macrocytosis
• Accompanying cytopenia in other cell lines
• Clinical suspicion of myelodysplastic syndrome 1

By following this systematic approach, the underlying cause of macrocytosis can be identified in more than 90% of cases 4, allowing for appropriate management and prevention of potential complications.