What is the diagnosis and treatment for macrocytic anemia with normal Hemoglobin and Platelet counts?

Macrocytosis Without Anemia: Diagnostic Workup and Management

This patient has isolated macrocytosis (MCV 103.1 fL) without anemia, requiring systematic evaluation for vitamin B12 deficiency, folate deficiency, medications, alcohol use, hypothyroidism, and liver disease before considering bone marrow disorders. 1, 2

Immediate Diagnostic Workup

Order the following tests immediately:

• Serum vitamin B12 level - deficiency defined as <150 pmol/L or <203 ng/L; if borderline (150-250 pmol/L), obtain methylmalonic acid level (>271 nmol/L confirms deficiency) 2
• Serum folate and RBC folate levels - deficiency indicated by serum folate <10 nmol/L (4.4 μg/L) or RBC folate <305 nmol/L 1, 2
• Reticulocyte count - differentiates megaloblastic causes (normal/low count) from hemolysis/hemorrhage (elevated count) 1, 2
• Peripheral blood smear - look specifically for macro-ovalocytes and hypersegmented neutrophils (≥5 lobes), which indicate megaloblastic anemia 3, 4
• TSH and free T4 - hypothyroidism causes non-megaloblastic macrocytosis 1, 2
• Liver function tests - chronic liver disease is a common cause of macrocytosis 3

Medication and Substance Review

Immediately review for these causative agents:

• Methotrexate - inhibits dihydrofolate reductase, blocking DNA synthesis 3
• Azathioprine/6-mercaptopurine - causes direct myelosuppression 3
• Hydroxyurea - well-established cause of drug-induced macrocytosis 1, 3
• Alcohol use - one of the most common causes of non-megaloblastic macrocytosis 3, 4

Critical Diagnostic Pitfall

Check RBC distribution width (RDW) and MCH to detect masked iron deficiency:

• Concurrent iron deficiency with B12/folate deficiency produces falsely normal MCV as microcytosis and macrocytosis cancel each other out 3
• Elevated RDW (>15%) suggests mixed microcytic and macrocytic populations 1, 3
• Reduced MCH (<27 pg) despite macrocytosis indicates coexisting iron deficiency requiring different treatment 3

Treatment Algorithm Based on Findings

If Vitamin B12 Deficiency Confirmed:

Never initiate folate supplementation before ruling out and treating B12 deficiency - this can precipitate irreversible subacute combined degeneration of the spinal cord. 1, 2, 3

For patients without neurological symptoms:

• Cyanocobalamin 1 mg (1000 mcg) intramuscularly three times weekly for 2 weeks 1, 5
• Then 1 mg every 2-3 months for life 1, 5

For patients with neurological symptoms:

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 1, 2
• Then 1 mg every 2 months indefinitely 1, 2

If Folate Deficiency (After Excluding B12 Deficiency):

• Oral folic acid 5 mg daily for minimum 4 months 1, 2

If Hypothyroidism:

• Thyroid hormone replacement per endocrine guidelines 1

If Medication-Induced:

• Consider discontinuation or dose reduction of causative agent when clinically appropriate 1

Monitoring Response to Treatment

• Repeat complete blood count in 4 weeks 1, 2
• Acceptable response: hemoglobin increase ≥2 g/dL within 4 weeks (though this patient currently has normal hemoglobin, monitor for normalization of MCV) 1, 2
• Reticulocyte count should increase within 3-7 days of B12 replacement 5

When to Refer to Hematology

Refer if:

• Cause remains unclear after extensive evaluation 1
• Leucopenia and/or thrombocytopenia present (suggests myelodysplastic syndrome) 1
• Persistent macrocytosis despite adequate vitamin replacement 1
• Peripheral smear shows dysplastic features beyond hypersegmented neutrophils 2