How should I manage a patient diagnosed with beta‑thalassemia trait who has microcytic anemia but normal iron studies?

Management of Beta-Thalassemia Trait with Microcytic Anemia

No treatment is required for beta-thalassemia trait—this is a benign carrier state that does not benefit from iron supplementation and requires only genetic counseling and monitoring. 1

Confirm the Diagnosis

• Hemoglobin electrophoresis should have already been performed to establish the diagnosis of beta-thalassemia trait, typically showing elevated HbA2 (>3.5%) with or without elevated HbF. 1, 2
• The combination of microcytosis (low MCV) with normal or elevated ferritin and a low RDW (≤14.0%) strongly suggests thalassemia trait rather than iron deficiency. 1, 3
• If hemoglobin electrophoresis has not yet been done, order it immediately when you see microcytosis with normal iron studies, particularly in patients of Mediterranean, Middle Eastern, African, or Southeast Asian descent. 1, 2

Do NOT Treat with Iron

• Iron supplementation is contraindicated in beta-thalassemia trait when iron studies are normal, as it provides no benefit and may lead to iron overload over time. 2, 4
• The microcytic anemia in thalassemia trait is due to defective hemoglobin beta-chain synthesis, not iron deficiency, so iron cannot correct the underlying problem. 2, 5
• A common pitfall is misdiagnosing thalassemia trait as "treatment-resistant iron deficiency anemia" and continuing unnecessary iron supplementation for years. 4

Provide Genetic Counseling

• Refer the patient for genetic counseling, particularly if they are of reproductive age, as two carriers can produce offspring with beta-thalassemia major, which requires lifelong transfusions. 2, 6
• Screen the patient's partner if they are planning pregnancy, as the risk of having a child with beta-thalassemia major is 25% when both parents are carriers. 2
• Explain that beta-thalassemia trait is generally asymptomatic and does not require treatment or monitoring beyond routine care. 2, 6

Monitoring Strategy

• No specific hematologic monitoring is required for asymptomatic beta-thalassemia trait beyond routine complete blood counts during annual physical examinations. 2, 6
• The hemoglobin level in beta-thalassemia trait is typically mildly reduced (10-13 g/dL) but stable over time. 2
• Do not repeat iron studies unless there is clinical suspicion for concurrent iron deficiency (e.g., new gastrointestinal bleeding, heavy menstrual bleeding). 1

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency—always check iron studies and consider hemoglobin electrophoresis when ferritin is normal or elevated. 1, 3
• Do not continue iron supplementation in patients with confirmed thalassemia trait and normal iron stores, as this leads to unnecessary iron accumulation. 4
• Do not perform unnecessary gastrointestinal investigations in patients with confirmed thalassemia trait and normal iron studies, as the microcytosis is explained by the genetic disorder. 1
• Do not overlook combined deficiencies—iron deficiency can coexist with thalassemia trait, recognizable by elevated RDW and low ferritin. 1, 3

When to Investigate Further

• If ferritin is <30 μg/L, the patient has concurrent iron deficiency that requires investigation and treatment even in the presence of thalassemia trait. 1, 3
• If the patient develops new symptoms (severe fatigue, dyspnea, jaundice), consider beta-thalassemia intermedia or other complications requiring hematology referral. 6
• If hemoglobin drops significantly below the patient's baseline, investigate for other causes of anemia rather than attributing it to thalassemia trait alone. 2, 6