From the Guidelines
Diagnosing thalassemia requires a comprehensive approach involving blood tests and genetic analysis, with hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) being crucial for measuring different hemoglobin fractions. The initial diagnostic workup should include a complete blood count (CBC) with red blood cell indices, which typically shows microcytic anemia with reduced hemoglobin levels, decreased mean corpuscular volume (MCV), and decreased mean corpuscular hemoglobin (MCH) 1.
Key Diagnostic Steps
- Peripheral blood smear examination is essential, revealing microcytic hypochromic red cells, target cells, and sometimes nucleated red blood cells.
- Hemoglobin electrophoresis or HPLC should be performed to measure different hemoglobin fractions, with thalassemia showing characteristic patterns of abnormal hemoglobin levels (HbA, HbA2, HbF).
- For beta-thalassemia, elevated HbA2 (>3.5%) is diagnostic of the trait, while severe forms show absent or reduced HbA with increased HbF, as seen in patients with β-thalassemia major who require lifelong blood transfusions and iron chelation treatment 1.
Genetic Analysis and Family Screening
- Alpha-thalassemia diagnosis often requires genetic testing since hemoglobin electrophoresis may be normal in carriers.
- DNA analysis can identify specific gene mutations, which is particularly important for genetic counseling and prenatal diagnosis.
- Family screening is recommended when thalassemia is diagnosed, as it is an inherited disorder with implications for family planning.
Differentiating Thalassemia from Other Conditions
- Iron studies should be included to differentiate thalassemia from iron deficiency anemia, as both present with microcytic anemia but thalassemia patients typically have normal or elevated serum ferritin levels.
From the Research
Diagnosing Thalassemia
- Thalassemia can be diagnosed using a combination of routine blood tests, serum iron, and hemoglobin electrophoresis 2
- The use of capillary electrophoresis systems can also aid in the rapid diagnosis of thalassemias and other hemoglobinopathies 3
- A stepwise algorithmic approach can be used to diagnose hemoglobinopathies, starting with a detailed clinical history and hematologic evaluation, followed by protein-based analytic methods and nucleic acid-based methods 4
- Advances in laboratory tests, including complete blood count and molecular technologies, have improved the evaluation of hemoglobinopathies and thalassemia 5
Diagnostic Methods
- Routine blood tests can help identify patients with thalassemia, with higher MCV and MCH values often excluding the possibility of thalassemia 2
- Serum iron levels can provide a preliminary indication of thalassemia type, with higher levels representing a possibility of thalassemia 2
- Hemoglobin electrophoresis can indicate the presence of thalassemia, with abnormal results requiring further sequencing of rare mutations 2
- Capillary electrophoresis systems can separate and quantitate different hemoglobin components, aiding in the diagnosis of thalassemias and other hemoglobinopathies 3
Laboratory Tests
- Complete blood count (CBC) is a widely available modality used in the investigation of hemoglobin disorders 5
- Protein-based analytic methods, such as Hb electrophoresis or isoelectric focusing (IEF), cation exchange high performance liquid chromatography (HPLC), and reversed phase HPLC, can be used to diagnose hemoglobinopathies 4
- Nucleic acid-based methods, such as polymerase chain reaction (PCR), reverse transcribed (RT)-PCR, sequencing of genomic DNA, and sequencing of RT-PCR amplified globin cDNA, can be used to confirm the diagnosis of hemoglobinopathies 4