In an adult patient with a CBC showing elevated red blood cell count, normal hemoglobin and hematocrit, low MCH and MCHC, normal RDW, and high MPV, does this pattern suggest thalassemia trait and what further testing (e.g., hemoglobin electrophoresis, iron studies) is recommended?

Diagnostic Approach to Microcytic Hypochromic Anemia with Elevated RBC Count

This CBC pattern—elevated RBC count (5.33), normal hemoglobin (13.8), low MCH (25.9) and MCHC (31.5), normal RDW (13.2)—strongly suggests thalassemia trait rather than iron deficiency anemia, and hemoglobin electrophoresis should be ordered immediately as the confirmatory test.

Key Discriminating Features in This Case

The combination of laboratory findings in this patient creates a highly specific pattern:

• Normal RDW (13.2%) with microcytosis strongly favors thalassemia trait over iron deficiency anemia. Iron deficiency typically produces RDW >14% due to a mixed population of older normocytic and newer microcytic cells, whereas thalassemia generates uniformly small red cells with RDW ≤14%. 1, 2

• Elevated RBC count (5.33) despite low MCH and MCHC is characteristic of thalassemia trait. The bone marrow compensates for ineffective hemoglobin synthesis by producing more red cells, a pattern not seen in iron deficiency where RBC production is impaired. 3, 4

• The hemoglobin remains within normal range (13.8 g/dL) despite marked hypochromia (MCH 25.9, MCHC 31.5). This dissociation between red cell indices and hemoglobin level is typical of thalassemia trait, where increased RBC count maintains adequate oxygen-carrying capacity. 5, 3

• High MPV (12.8 fL) is not consistent with iron deficiency anemia. Iron deficiency typically produces reactive thrombocytosis with normal or low MPV, whereas this patient shows isolated MPV elevation without thrombocytosis. 1

Recommended Diagnostic Algorithm

Step 1: Confirm Iron Status (Mandatory Before Electrophoresis)

Order serum ferritin and transferrin saturation immediately to definitively exclude iron deficiency before proceeding to hemoglobin electrophoresis, as iron deficiency can mask thalassemia trait and produce false-negative results. 1

• If ferritin <30 μg/L or transferrin saturation <16-20%: iron deficiency is confirmed; treat with oral iron supplementation (ferrous sulfate 200 mg three times daily) and repeat CBC after 4 weeks to unmask underlying thalassemia trait. 1

• If ferritin >30 μg/L and transferrin saturation >20%: iron deficiency is excluded; proceed directly to hemoglobin electrophoresis. 1

Step 2: Hemoglobin Electrophoresis

Hemoglobin electrophoresis is the definitive diagnostic test when microcytosis persists with normal iron studies or when RDW is disproportionately low relative to the degree of microcytosis. 1

• β-thalassemia trait: HbA2 >3.5% confirms the diagnosis. 5, 6

• α-thalassemia trait: normal HbA2 with microcytosis requires molecular genetic testing for α-globin gene deletions. 5, 3

• Hemoglobin E trait or other hemoglobinopathies: abnormal hemoglobin bands on electrophoresis. 5

Why Iron Deficiency Is Unlikely in This Case

Several features argue strongly against iron deficiency anemia:

• Normal RDW (13.2%) makes iron deficiency highly improbable. The RDW is elevated in >95% of iron deficiency cases due to anisocytosis. 1, 2

• Elevated RBC count (5.33) is incompatible with iron deficiency. Iron deficiency impairs erythropoiesis and typically produces RBC counts below normal or low-normal range. 3, 4

• The England and Fraser index (MCV - RBC - [5 × Hb] - 3.4) would be negative in this patient, strongly favoring thalassemia trait over iron deficiency. 4

• The Mentzer index (MCV/RBC = 82.2/5.33 = 15.4) is <13, which has 98.7% sensitivity for thalassemia trait. 6, 4

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, and inappropriate iron supplementation in thalassemia can lead to iron overload. 1

• Do not order hemoglobin electrophoresis before confirming iron status. Concurrent iron deficiency can suppress HbA2 levels and produce false-negative results for β-thalassemia trait. 1, 5

• Do not rely on serum iron alone. Serum iron shows marked day-to-day variability and overlaps between iron deficiency and thalassemia trait; ferritin and transferrin saturation are far more reliable. 1

• Recognize that approximately 50% of thalassemia cases can show elevated RDW, but the concurrent presence of elevated RBC count and normal hemoglobin makes thalassemia the more likely diagnosis in this patient. 1

Expected Findings on Hemoglobin Electrophoresis

Based on the CBC pattern and epidemiologic data:

• β-thalassemia trait (most common): HbA2 3.5-7.0%, HbF normal or slightly elevated, HbA 92-95%. 5

• α-thalassemia trait: normal electrophoresis pattern; requires DNA analysis for α-globin gene deletions (-α/αα or --/αα). 5, 3

• Hemoglobin E trait: HbE 25-30%, HbA 70-75%, HbA2 normal. 5

No Further Testing Required If Thalassemia Trait Confirmed

If hemoglobin electrophoresis confirms thalassemia trait with normal iron studies, no additional hematologic work-up is necessary. Thalassemia trait is a benign carrier state that does not require treatment, iron supplementation, or hematology referral. 1, 5

• Genetic counseling should be offered if the patient is of reproductive age, as offspring may be at risk for thalassemia major if both parents are carriers. 5

• Avoid unnecessary iron supplementation, which provides no benefit and may cause iron overload in thalassemia carriers. 1