Could an adult woman with microcytic, hypochromic anemia (low Mean Corpuscular Volume (MCV) and low Mean Corpuscular Hemoglobin (MCH)) and laboratory values indicating severe anemia (low hemoglobin and low hematocrit) have thalassemia?

Diagnostic Approach to Microcytic Hypochromic Anemia

This presentation is highly suggestive of iron deficiency anemia, but thalassemia trait must be ruled out before initiating iron therapy. The key distinguishing feature is that thalassemia typically presents with MCV disproportionately low relative to the degree of anemia, whereas iron deficiency shows a more proportionate relationship 1.

Immediate Diagnostic Steps

Order serum ferritin and red blood cell distribution width (RDW) immediately to differentiate between these two conditions. 1

• If ferritin <15 μg/L: This confirms absent iron stores and establishes iron deficiency anemia as the diagnosis 1
• If ferritin <30 μg/L: This indicates low body iron stores consistent with iron deficiency 1
• If ferritin <45 μg/L: This provides optimal sensitivity/specificity trade-off for iron deficiency in clinical practice 1

The RDW is critical for distinguishing these conditions: 1

• RDW >14.0% with low MCV: Strongly indicates iron deficiency anemia 1
• RDW ≤14.0% with low MCV: Suggests thalassemia trait 1

Why This Matters Clinically

The distinction is crucial because:

• Iron deficiency requires investigation of the source of blood loss (gastrointestinal bleeding, menstrual losses, malabsorption) and iron replacement 1
• Thalassemia trait requires no iron therapy and giving unnecessary iron can lead to iron overload 2
• Hemoglobin electrophoresis should be ordered if microcytosis persists with normal iron studies, particularly in patients of Mediterranean, Middle Eastern, African, or Southeast Asian descent 1

Additional Diagnostic Considerations

MCH is actually more reliable than MCV for detecting iron deficiency because it is less dependent on storage conditions and the counting machine used, and it decreases in both absolute and functional iron deficiency 1. Your patient's MCH of 17.2 is markedly reduced, which supports iron deficiency.

Transferrin saturation should be added if ferritin appears falsely normal due to inflammation or chronic disease. 3

• TSAT <16-20% confirms iron deficiency 3
• In the presence of inflammation, ferritin up to 100 μg/L may still represent iron deficiency 3

Diagnostic Algorithm

1. Check serum ferritin and RDW first 1
2. If ferritin <45 μg/L AND RDW >14.0%: Diagnose iron deficiency anemia and investigate the source of iron loss 1
3. If ferritin normal AND RDW ≤14.0%: Order hemoglobin electrophoresis to evaluate for thalassemia trait 1
4. If ferritin normal AND RDW >14.0%: Consider adding transferrin saturation and inflammatory markers (CRP) to assess for anemia of chronic disease 3

Critical Pitfalls to Avoid

Do not assume all microcytic anemia is iron deficiency. Thalassemia trait, anemia of chronic disease, and sideroblastic anemia require different management strategies 3.

Do not start iron therapy without confirming iron deficiency, as this can mask thalassemia trait and lead to unnecessary iron accumulation 2.

In adults with confirmed iron deficiency, investigation of the source is mandatory. For non-menstruating women with hemoglobin <100 g/L (your patient has 90 g/L), fast-track gastrointestinal referral is warranted to exclude malignancy 1.

Expected Response to Confirm Diagnosis

If iron deficiency is confirmed and iron therapy initiated, expect hemoglobin to rise ≥10 g/L within 2 weeks. 3 This response confirms the diagnosis even if initial iron studies were equivocal. Failure to respond requires re-evaluation for malabsorption, ongoing blood loss, non-compliance, or rare genetic disorders of iron metabolism 3.