What additional labs are recommended for a patient with microcytosis (Mean Corpuscular Volume (MCV) < 50)?

Additional Laboratory Tests for Severe Microcytosis (MCV < 50)

For patients with severe microcytosis (MCV < 50), a comprehensive workup should include serum ferritin, transferrin saturation, red cell distribution width (RDW), hemoglobin electrophoresis, and complete iron studies to differentiate between iron deficiency anemia and hemoglobinopathies. 1

Initial Laboratory Assessment

When evaluating severe microcytosis (MCV < 50), the following tests should be ordered:

1. Iron Studies:

   • Serum ferritin (most specific test for iron deficiency)
   • Transferrin saturation
   • Serum iron
   • Total iron-binding capacity (TIBC)

2. Red Blood Cell Indices:

   • Red cell distribution width (RDW)
   • Mean corpuscular hemoglobin (MCH)
   • Percentage of hypochromic red cells

3. Hemoglobin Analysis:

   • Hemoglobin electrophoresis (to rule out hemoglobinopathies)
   • HbA2 measurement (for beta-thalassemia trait)

Interpretation of Results

Iron Deficiency Anemia

• Serum ferritin < 15 μg/L is highly specific for iron deficiency (specificity 0.99) 1
• Ferritin < 45 μg/L with inflammation may still indicate iron deficiency 1
• Low MCH (hypochromia) and low MCV (microcytosis) 1
• Elevated RDW > 14.0% (indicates variation in red cell size) 1
• Low transferrin saturation 1

Thalassemia Trait

• Normal or elevated ferritin 1
• Severely low MCV (often disproportionate to the degree of anemia) 1
• Normal RDW (≤ 14.0%) 1
• Elevated HbA2 (in beta-thalassemia trait) 2

Diagnostic Algorithm

1. First step: Measure serum ferritin

   • If ferritin < 15 μg/L: Confirm iron deficiency anemia
   • If ferritin 15-45 μg/L: Check inflammatory markers (CRP)
   • If ferritin > 45 μg/L: Consider other causes

2. Second step: Evaluate RDW

   • RDW > 14.0% with low ferritin: Strongly suggests iron deficiency anemia 1
   • RDW ≤ 14.0% with normal ferritin: Suggests thalassemia trait 1

3. Third step: Perform hemoglobin electrophoresis

   • Required to rule out hemoglobinopathies, especially with normal ferritin 1
   • Essential in patients with ethnic backgrounds where thalassemia is common

Additional Considerations

• Inflammatory conditions: Check CRP to identify inflammation that may mask iron deficiency (ferritin is an acute phase reactant) 1
• Lead toxicity: Consider in children with unexplained microcytosis 1
• Sideroblastic anemia: Consider in patients with microcytic anemia and elevated ferritin 1
• Genetic disorders: For severe microcytosis resistant to iron therapy, consider genetic testing for rare disorders like SLC11A2 defects 1

Important Caveats

• An MCV < 50 is extremely low and highly suggestive of either severe iron deficiency or a hemoglobinopathy (particularly thalassemia)
• Coexisting conditions (vitamin B12/folate deficiency) may mask the degree of microcytosis 1
• In patients with inflammatory conditions, ferritin may appear normal despite iron deficiency 1
• Once iron deficiency is confirmed, the source of blood loss must be identified, particularly in adults where gastrointestinal malignancy must be considered 2

Follow-up Testing

If iron deficiency is confirmed, investigate the underlying cause:

• Gastrointestinal evaluation (endoscopy, colonoscopy) in adults
• Menstrual blood loss assessment in premenopausal women
• Nutritional assessment in all patients
• Celiac disease screening (anti-endomysial antibodies) 1

If thalassemia is suspected, family testing and genetic counseling should be considered.