Detection of Hemoglobin E on Complete Blood Count
A standard CBC cannot directly detect hemoglobin E—you need hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) to definitively identify this variant. However, specific CBC abnormalities should prompt you to order these confirmatory tests.
CBC Findings That Should Raise Suspicion for Hemoglobin E
Red Blood Cell Indices
- Microcytic hypochromic anemia with low mean corpuscular volume (MCV) is the hallmark finding that should trigger further investigation 1, 2
- Elevated red cell distribution width-coefficient of variation (RDW-CV) indicates heterogeneous red cell populations 1
- Normal to elevated red blood cell count despite the microcytosis distinguishes hemoglobin E from iron deficiency anemia 1
Peripheral Blood Smear Findings
- Target cells are characteristic and should be specifically looked for on manual review 1
- Microcytic hypochromic red cells without the severe poikilocytosis seen in iron deficiency 1
Critical Distinction: CBC Alone Is Insufficient
The CBC provides clues but cannot make the diagnosis. When you see microcytic anemia with target cells in an otherwise healthy individual, particularly those of Southeast Asian descent, you must order 3, 4:
- Hemoglobin electrophoresis as the traditional screening method
- HPLC as the preferred modern diagnostic technique that can quantify hemoglobin variants 4, 2
Diagnostic Confirmation by HPLC
Once HPLC is performed, hemoglobin E will show 1, 2:
- Very high percentage of hemoglobin E (approaching 100% in homozygous HbEE)
- Very low or absent hemoglobin A2
- Normal proportions of hemoglobin F
- In heterozygous HbE trait, approximately 25-30% hemoglobin E with normal hemoglobin A 2, 5
Clinical Context for Otherwise Healthy Individuals
Homozygous hemoglobin E (HbEE) and hemoglobin E trait are mild disorders that typically do not cause symptoms in otherwise healthy individuals 5. The key clinical scenarios where CBC abnormalities lead to incidental detection include:
- Routine health screening showing unexplained microcytosis 1
- Evaluation for unrelated conditions (such as diabetes screening in the reported case) 1
- Pre-employment or insurance medical examinations 4
Common Diagnostic Pitfalls to Avoid
Do not assume microcytic anemia equals iron deficiency—hemoglobin E is extremely common in Asian populations and will not respond to iron supplementation 3, 2. The combination of microcytosis with normal or elevated RBC count should immediately prompt hemoglobin variant testing rather than empiric iron therapy 1.
Borderline HbA2 values on HPLC can cause diagnostic confusion, particularly when trying to distinguish between hemoglobin E trait and beta thalassemia trait, as both can present with similar CBC findings 2. In these cases, genetic testing may be required for definitive diagnosis 2.
Family screening should be recommended once hemoglobin E is confirmed, as this is an inherited condition with implications for offspring, particularly if the partner also carries a hemoglobin variant 1, 5.