What are the initial steps in the workup and management of a patient suspected of having thalassemia?

From the Guidelines

The initial workup for suspected thalassemia should begin with a complete blood count (CBC) with peripheral blood smear, hemoglobin electrophoresis, and serum ferritin measurement. The CBC typically reveals microcytic hypochromic anemia with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while the peripheral smear may show target cells, microcytosis, and hypochromia. Hemoglobin electrophoresis is essential to identify abnormal hemoglobin patterns characteristic of different thalassemia types, such as elevated HbA2 in beta-thalassemia minor or absence of beta chains in beta-thalassemia major. Serum ferritin helps differentiate thalassemia from iron deficiency anemia, as ferritin is typically normal or elevated in thalassemia but low in iron deficiency.

Some key points to consider in the workup and management of thalassemia include:

• The importance of early identification of cardiac iron overload in patients with beta-thalassemia major, as heart failure is the most common cause of death in these patients 1
• The use of cardiac T2* magnetic resonance to estimate cardiac iron, with a value of <10 ms being a predictor of heart failure development 1
• The need for urgent consultation with a center with expertise in managing acute decompensated heart failure in patients with thalassemia 1
• The role of iron chelation therapy, such as deferasirox, deferiprone, or deferoxamine, in managing iron overload in patients with transfusion-dependent thalassemia
• The potential need for hematopoietic stem cell transplantation in severe cases of thalassemia

Management depends on the type and severity of thalassemia, ranging from observation and folic acid supplementation (1 mg daily) for mild forms to regular blood transfusions, iron chelation therapy, and potential hematopoietic stem cell transplantation for severe forms. Patients with transfusion-dependent thalassemia require monitoring of iron overload through serum ferritin levels and cardiac/liver MRI. This comprehensive approach is necessary because thalassemias are genetic disorders of hemoglobin synthesis that result in reduced or absent production of specific globin chains, leading to imbalanced globin chain production and ineffective erythropoiesis.

From the Research

Initial Steps in Thalassemia Workup

The initial steps in the workup of a patient suspected of having thalassemia include:

• Suspecting thalassemia in patients with microcytic anemia and normal or elevated ferritin levels 2
• Performing hemoglobin electrophoresis to reveal common characteristics of different thalassemia subtypes 2, 3, 4
• Conducting genetic testing to confirm the diagnosis 2, 4, 5
• Obtaining a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography, including quantitation of HbA2 and HbF 3
• Investigating patients with microcytosis and/or hypochromia with a brilliant cresyl blue stained blood smear to identify H bodies, and performing a serum ferritin test to exclude iron deficiency anemia 3

Screening and Diagnosis

Screening for thalassemia and hemoglobinopathies should be offered to individuals at increased risk, including those from ethnic populations with a higher prevalence of these conditions 3

• Screening should ideally be done pre-conceptionally or as early as possible in pregnancy 3
• If a woman's initial screening is abnormal, her partner should also be screened 3
• If both partners are found to be carriers of thalassemia or an Hb variant, they should be referred for genetic counseling 3
• Prenatal diagnosis should be offered to pregnant women/couples at risk of having a fetus affected with a clinically significant thalassemia or hemoglobinopathy 3, 4

Classification and Diagnosis

Thalassemia diseases can be classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia 5

• Definitive diagnosis of thalassemia and hemoglobinopathies requires a comprehensive workup, including complete blood count, hemoglobin analysis, and molecular studies to identify mutations of globin genes 5
• Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains 6