How is microcytic anemia diagnosed?

Diagnosis of Microcytic Anemia

Microcytic anemia is determined by a mean corpuscular volume (MCV) <80 fL in adults, followed by serum ferritin as the most powerful initial diagnostic test to identify iron deficiency, the most common cause. 1, 2

Defining Microcytic Anemia

• MCV <80 fL (80 mcm³) defines microcytic anemia in adults, with age-specific parameters required for patients under 17 years 1, 3
• The diagnosis begins with a complete blood count (CBC) that reveals both low hemoglobin and low MCV 2

Initial Diagnostic Algorithm

Step 1: Measure Serum Ferritin

• Serum ferritin is the most powerful and specific test for iron deficiency, with <12 μg/L being diagnostic of iron deficiency 1
• Ferritin <15 μg/L indicates absent iron stores, while <30 μg/L generally indicates low body iron stores in the absence of inflammation 4, 5
• In the presence of inflammation or chronic disease, ferritin up to 100 μg/L may still be consistent with iron deficiency 4

Step 2: Use Red Cell Distribution Width (RDW) for Differentiation

• RDW >14% with low MCV indicates iron-deficiency anemia 1, 2
• RDW ≤14% with low MCV suggests thalassemia minor 1, 2

Step 3: Complete Iron Studies When Ferritin is Normal or Elevated

• Measure serum iron, total iron-binding capacity (TIBC), and transferrin saturation 2, 4
• Transferrin saturation <16-30% confirms iron deficiency 1, 2, 4
• Low iron with high TIBC and low ferritin confirms iron deficiency anemia 2, 6
• Low iron with low TIBC and normal/elevated ferritin suggests anemia of chronic disease 2, 4

Step 4: Assess Inflammatory Markers

• Elevated ESR, ZSR, or CRP indicate chronic disease rather than pure iron deficiency 1
• This distinction is critical because anemia of chronic disease causes functional iron deficiency through iron sequestration, not true depletion 1

Differential Diagnosis Beyond Iron Deficiency

When to Consider Thalassemia

• Very low MCV with elevated red cell count and normal iron studies suggests thalassemia 1, 4
• Hemoglobin electrophoresis should be performed, which typically shows elevated hemoglobin A2 in beta-thalassemia trait 2, 5

When to Consider Genetic Disorders

• If anemia is refractory to iron supplementation despite confirmed deficiency, consider genetic disorders of iron metabolism or heme synthesis 1
• Sideroblastic anemias present with elevated ferritin and transferrin saturation even before transfusions, requiring bone marrow examination showing ring sideroblasts 1

Rare Genetic Causes

• Iron-refractory iron-deficiency anemia (IRIDA) presents in childhood with remarkably low transferrin saturation, low-to-normal ferritin, and failure to respond to oral iron 1
• DMT1 deficiency causes paradoxical systemic iron loading with increased transferrin saturation 1

Common Pitfalls to Avoid

• Failing to consider mixed anemias can lead to incorrect diagnosis, as microcytosis and macrocytosis can neutralize each other, resulting in a falsely normal MCV 2
• Do not overlook NSAID use as a common cause of occult gastrointestinal blood loss leading to iron deficiency 1
• In adults with confirmed iron deficiency, gastrointestinal blood loss must be investigated as the presumed source, with consideration of gastrointestinal malignancy 4, 5
• Bone marrow aspiration remains the definitive test when other studies are equivocal, though it is rarely needed with modern laboratory testing 1, 7