From the Guidelines
A thalassemia workup should begin with a complete blood count (CBC) with peripheral blood smear, hemoglobin electrophoresis, and quantitative hemoglobin analysis, as these initial tests help identify the presence and type of thalassemia 1. The CBC typically shows microcytic, hypochromic anemia with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH).
Key Tests
- Hemoglobin electrophoresis and high-performance liquid chromatography (HPLC) are essential to measure different hemoglobin fractions, including HbA, HbA2, HbF, and any abnormal hemoglobins.
- For alpha thalassemia, genetic testing is often necessary since electrophoresis may not be diagnostic.
- Additional tests should include serum ferritin to rule out iron deficiency, which can coexist with thalassemia.
- Liver function tests, renal function tests, and serum iron studies are important for patients with significant anemia.
Monitoring Iron Overload
For patients with beta thalassemia major or intermedia, regular monitoring of iron overload through serum ferritin and transferrin saturation is crucial, with consideration of cardiac T2* MRI and liver iron concentration assessment in those receiving regular transfusions, as cardiac iron accumulation is a major cause of morbidity and mortality in these patients 1.
Family Screening
Family screening is recommended for genetic counseling purposes, as thalassemia follows autosomal recessive inheritance patterns. This comprehensive approach allows for accurate diagnosis, appropriate management, and prevention of complications related to thalassemia.
From the Research
Thalassemia Workup
- Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin 2
- The diagnosis of thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels 2
- Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis 2
Diagnostic Approach
- Serum ferritin measurement and noninvasive imaging techniques are available to diagnose iron overload, quantify its extent in different organs, and monitor clinical response to therapy 3
- Genetic counseling and screening in high-risk populations can assist in reducing the prevalence of thalassemia 2
Complications and Treatment
- Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues 2
- Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload, hydroxyurea, hematopoietic stem cell transplantation, and luspatercept 2
- Iron overload is associated with increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) 3
Types of Thalassemia
- Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth 2
- Beta-thalassemia major requires lifelong transfusions starting in early childhood (often before two years of age) 2
- Alpha- and beta-thalassemia intermedia have variable presentations based on gene mutation or deletion, with mild forms requiring only monitoring but more severe forms leading to symptomatic anemia and requiring transfusion 2