How does hemoglobin E trait affect complete blood count parameters (MCV, MCH, RDW, hemoglobin, RBC count, white‑blood‑cell count, platelet count), particularly in individuals of Southeast Asian descent?

Hemoglobin E Trait Effects on Complete Blood Count

Hemoglobin E trait produces mild microcytic anemia with characteristically low MCV and MCH, but importantly maintains a normal or only slightly elevated RDW, which distinguishes it from iron deficiency anemia. 1, 2

Red Blood Cell Indices

Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH)

• Hemoglobin E trait consistently produces microcytosis with MCV typically >70 fL but <80 fL, and MCH typically >23 pg but <27 pg. 1, 3
• A negative correlation exists between HbA2/E peak values and both MCV and MCH—as the percentage of HbE increases, these indices decrease proportionally. 1, 3
• The microcytosis in HbE trait reflects the mild thalassemic phenotype of this variant, as HbE is produced at a slightly reduced rate compared to normal hemoglobin. 4

Red Cell Distribution Width (RDW)

• RDW remains normal or only minimally elevated in HbE trait (typically <14.5%), which is the single most useful parameter to distinguish it from iron deficiency anemia. 2
• A positive correlation exists between HbA2/E levels and RDW, meaning higher percentages of HbE produce slightly higher RDW values, but these typically remain below the threshold seen in iron deficiency. 1
• Using an RDW cutoff of 14.45 in screening protocols increases the sensitivity for detecting HbE trait to 98.2%, compared to 86.6% when using only MCV and MCH criteria. 2

Mean Corpuscular Hemoglobin Concentration (MCHC)

• MCHC is typically normal or only minimally reduced in HbE trait, unlike the more pronounced reduction seen in iron deficiency anemia. 1, 3

Hemoglobin and Red Blood Cell Count

• Hemoglobin levels in HbE trait are normal or show only mild reduction (typically >11 g/dL in women, >12 g/dL in men), distinguishing this condition from clinically significant anemias. 3, 5
• Red blood cell count is typically normal or mildly elevated as a compensatory mechanism for the mild microcytosis. 3, 5
• The combination of mild or absent anemia with microcytosis creates a characteristic pattern where the RBC count may appear disproportionately normal relative to the low MCV. 5

White Blood Cell and Platelet Counts

• White blood cell count and platelet count remain completely normal in HbE trait, as this is purely a red cell disorder. 5
• Any abnormalities in these parameters should prompt investigation for alternative or additional diagnoses. 5

Clinical Implications for Southeast Asian Populations

• HbE trait is clinically benign and requires no treatment, but identification is critical for genetic counseling because compound heterozygosity with β-thalassemia produces severe transfusion-dependent disease. 3, 4
• Approximately 50% of all severe β-thalassemia cases globally are HbE/β-thalassemia compound heterozygotes, making carrier detection in Southeast Asian populations a public health priority. 4
• When a patient from Southeast Asia presents with microcytic indices (MCV <80, MCH <27) but normal or minimally elevated RDW (<14.5), HbE trait should be the primary diagnostic consideration rather than iron deficiency. 2

Diagnostic Pitfalls and Confounding Factors

Iron Deficiency Coexistence

• Iron deficiency can coexist with HbE trait and will elevate the RDW above 14.5%, potentially masking the underlying hemoglobinopathy. 5
• When iron deficiency is corrected through supplementation, the characteristic HbE trait pattern (microcytosis with normal RDW) becomes apparent. 5
• Always measure serum ferritin and transferrin saturation in microcytic patients from Southeast Asia before concluding the diagnosis is solely iron deficiency. 5

Alpha-Thalassemia Coinheritance

• Coinheritance of α-thalassemia with HbE trait does not significantly alter the CBC parameters beyond what is seen with HbE trait alone. 5
• However, comprehensive DNA analysis for α-thalassemia becomes essential when the partner of an HbE trait carrier is suspected of carrying α-thalassemia 1, as their offspring could develop HbH disease. 5

Hemoglobin F Elevation

• Approximately 16% of HbE trait carriers (12 out of 76 in one study) demonstrate substantial HbF elevation, which can lead to misdiagnosis as HbE/β-thalassemia if hemoglobin analysis alone is used. 5
• Clinical correlation is essential—HbE trait carriers are asymptomatic, never require transfusion, and have no hepatosplenomegaly, whereas HbE/β-thalassemia patients present with thalassemia intermedia or major phenotypes. 3, 5

Screening Algorithm for Southeast Asian Populations

When evaluating microcytic anemia in patients of Southeast Asian descent:

1. If MCV <80 fL and MCH <27 pg with RDW <14.5%: Strongly suspect HbE trait and proceed directly to hemoglobin analysis by HPLC or electrophoresis. 2

2. If MCV <80 fL and MCH <27 pg with RDW >14.5%: Consider iron deficiency, but also measure iron studies and perform hemoglobin analysis, as coexistent conditions are common. 1, 5

3. If hemoglobin analysis shows HbE peak of 25-35%: Confirm HbE trait diagnosis and provide genetic counseling regarding reproductive risks. 3

4. If partner screening is indicated: Perform comprehensive hemoglobin analysis and consider α-thalassemia DNA testing to assess risk of severe compound heterozygous states in offspring. 5, 4