Distinguishing Thalassemia Trait from Iron Deficiency in Microcytic Anemia
Your microcytic anemia with low serum iron and elevated RDW is most likely iron deficiency anemia, not thalassemia trait, because thalassemia typically presents with normal or only mildly elevated RDW (≤14%), whereas your elevated RDW strongly suggests iron deficiency. 1, 2
Key Diagnostic Algorithm
Step 1: Evaluate RDW in Context with MCV
- A low MCV with RDW >14.0% indicates iron deficiency anemia, while a low MCV with RDW ≤14.0% suggests thalassemia minor 1, 2
- Your elevated RDW makes thalassemia trait unlikely, as thalassemia produces more uniform (homogeneous) red cells with normal RDW in most cases 1
- However, this rule has important limitations: nearly half of thalassemia cases can show elevated RDW, so RDW alone cannot definitively exclude thalassemia 3, 4
Step 2: Confirm Iron Deficiency with Serum Ferritin
- Serum ferritin is the single most powerful test for iron deficiency 1, 2
- Ferritin <15 μg/L confirms absent iron stores with 99% specificity 2
- Ferritin <30 μg/L indicates low body iron stores 2
- A cut-off of 45 μg/L provides optimal sensitivity and specificity in clinical practice 2
- Your low serum iron combined with microcytosis and elevated RDW strongly supports iron deficiency rather than thalassemia 1
Step 3: Add Transferrin Saturation if Needed
- Transferrin saturation <16-20% confirms iron deficiency, particularly when ferritin might be falsely elevated by inflammation 2
- This test is more sensitive than hemoglobin alone for detecting iron deficiency 1
When to Consider Hemoglobin Electrophoresis
Order hemoglobin electrophoresis only if:
- Iron studies (ferritin and transferrin saturation) are normal or borderline 2
- MCV is disproportionately low relative to the degree of anemia 2
- Patient has appropriate ethnic background (African, Mediterranean, or Southeast Asian ancestry) 1
- Anemia fails to respond to 4 weeks of adequate iron therapy despite compliance 1
Critical Pitfalls to Avoid
- Do not assume normal RDW rules out iron deficiency: some iron-deficient patients have normal RDW, especially in early or mild deficiency 3, 4
- Do not assume elevated RDW rules out thalassemia: approximately 70% of thalassemia trait cases show elevated RDW 4
- Do not order hemoglobin electrophoresis prematurely: first confirm whether iron deficiency is present with ferritin and transferrin saturation 2
- Do not overlook combined deficiencies: iron deficiency can coexist with folate or B12 deficiency, which may be recognized by elevated RDW 1
Practical Clinical Approach
Given your presentation of microcytic anemia with both low serum iron AND elevated RDW, the probability of iron deficiency is approximately 90% 5. Begin oral iron supplementation (ferrous sulfate 200 mg three times daily) immediately while completing your diagnostic workup 2. If hemoglobin rises by ≥10 g/L within 2 weeks, this confirms iron deficiency even when other tests are equivocal 2.
Hemoglobin electrophoresis becomes necessary only if you fail to respond to adequate iron therapy after 4 weeks, at which point thalassemia trait or other hemoglobinopathies should be investigated 1, 2.