Hemoglobin E Trait with Microcytic Anemia
This patient has Hemoglobin E trait (heterozygous HbE), which is causing the microcytic anemia with low Hemoglobin A (72.8%) and elevated Hemoglobin E (24.4%), and typically requires no treatment beyond monitoring and genetic counseling. 1
Diagnosis
The hemoglobin electrophoresis pattern is diagnostic:
- Hemoglobin E trait is confirmed by the presence of approximately 24-25% Hemoglobin E with reduced Hemoglobin A (72.8%) and normal Hemoglobin A2 (2.8%) 1, 2
- The microcytosis (MCV 75.5 fL) with elevated RDW (16.9%) is characteristic of hemoglobin E disorders, distinguishing it from thalassemia minor which typically shows low MCV with RDW ≤14.0% 1, 3
- The mild anemia (Hb 9.3 g/dL) with microcytosis and hypochromia (MCH 22.3 pg) is expected in HbE trait 4, 5
Key Distinguishing Features
- Iron deficiency is unlikely because the RDW pattern and hemoglobin electrophoresis results point to a hemoglobinopathy rather than nutritional deficiency 6, 4
- The normal Hemoglobin F (<1.0%) and Hemoglobin A2 (2.8%) help exclude beta-thalassemia trait, which would show elevated HbA2 (>3.2%) 1, 5
- Serum ferritin should still be checked to exclude coexisting iron deficiency, as combined deficiencies can occur 1, 2
Treatment Approach
Primary Management
- No specific treatment is required for Hemoglobin E trait itself, as it is a benign carrier state 1, 2
- Avoid unnecessary iron supplementation unless concurrent iron deficiency is documented by serum ferritin <30 μg/L or <45 μg/L for optimal sensitivity 1, 2
- If iron deficiency is confirmed, treat with ferrous sulfate 200 mg three times daily for at least three months after correction of anemia 1, 2
Important Caveats
- Do not misdiagnose as iron deficiency anemia based solely on microcytosis and low hemoglobin—the hemoglobin electrophoresis is definitive 6, 4
- Avoid repeated unnecessary trials of iron therapy when the underlying cause is a hemoglobinopathy 6, 5
- Iron studies (serum ferritin, iron, TIBC, transferrin saturation) should be obtained to definitively exclude coexisting iron deficiency 1, 7
Monitoring and Genetic Counseling
Follow-up Recommendations
- Monitor hemoglobin concentration and red cell indices at three-monthly intervals initially, then annually 1, 2
- Provide additional evaluation if hemoglobin drops significantly below current baseline 1, 2
- Genetic counseling is essential because if the patient's partner also carries a hemoglobin variant (HbE or beta-thalassemia), their offspring could have Hemoglobin E disease or HbE/beta-thalassemia, which can cause significant morbidity 8, 1
Family Screening
- Screen the patient's partner for hemoglobin variants, especially if considering pregnancy or if from Southeast Asian descent where HbE is prevalent 8, 1
- First-degree family members should be offered screening to identify other carriers 8, 1
- Referral to a clinical geneticist may be appropriate for reproductive counseling if both partners carry hemoglobin variants 8
Clinical Context
- Hemoglobin E is one of the most common hemoglobin variants worldwide, particularly prevalent in Southeast Asian populations 5
- Heterozygous HbE trait causes mild microcytic anemia that is clinically benign and does not progress 4, 5
- The main clinical significance is reproductive risk if both partners carry hemoglobin variants 8, 1