What is the test for diagnosing thalassemia?

Diagnostic Tests for Thalassemia

The primary diagnostic approach for thalassemia involves a complete blood count (CBC) with red cell indices, hemoglobin analysis, and genetic testing when necessary. 1

Initial Laboratory Assessment

• Mean Corpuscular Volume (MCV) is typically low in thalassemia trait, with values often below the 5th percentile for age 1
• Red Blood Cell (RBC) count is often normal or elevated in thalassemia trait, in contrast to iron deficiency anemia where it is typically low 1
• Red Blood Cell Distribution Width (RDW) is a critical differentiating factor: RDW ≤14.0% suggests thalassemia trait, while RDW >14.0% suggests iron deficiency anemia 1
• Peripheral blood smear examination is essential to confirm the size, shape, and color of RBCs 2

Hemoglobin Analysis

• Hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), or capillary zone electrophoresis (CE) are used to identify abnormal hemoglobin patterns 3
• HbA2 measurement is crucial for beta-thalassemia diagnosis, with elevated levels being characteristic 1
• Important: HbA2 measurement should be performed after iron deficiency has been corrected, as iron deficiency can falsely lower HbA2 levels 1

Additional Testing

• Serum ferritin should be measured to rule out concurrent iron deficiency, which can mask thalassemia trait characteristics 1
• If iron deficiency is present (ferritin below reference range), iron replacement therapy should be provided before final assessment for thalassemia trait 1

Genetic Testing

• DNA analysis is required for specific thalassemia mutation diagnosis 3
• For alpha-thalassemia: techniques to detect large gene deletions are used 3
• For beta-thalassemia: point mutation detection methods are employed 3
• Prenatal diagnosis can be performed using genetic testing of amniotic fluid or chorionic villus sampling 4, 5

Diagnostic Algorithm

1. Start with CBC and red cell indices (MCV, RBC count, RDW)
2. If microcytic anemia is present with normal/elevated RBC count and normal/low RDW, proceed to hemoglobin analysis
3. Measure serum ferritin to rule out iron deficiency
4. Perform hemoglobin analysis (HPLC or CE) to quantify HbA2, HbF, and detect abnormal hemoglobins
5. If hemoglobin analysis suggests thalassemia, confirm with genetic testing for specific mutations 3

Common Pitfalls and Caveats

• Concurrent iron deficiency can mask the typical laboratory findings of thalassemia trait, particularly HbA2 elevation in beta-thalassemia trait 1
• Lead poisoning, anemia of chronic inflammation, and sickle cell trait can present with similar red cell indices and must be excluded 1
• The reticulocyte count is an important parameter to distinguish between decreased production (low reticulocyte index) and increased destruction or loss of RBCs (high reticulocyte index) 2
• Alpha thalassemia cannot be reliably diagnosed by hemoglobin electrophoresis alone and requires genetic testing 3