What is the workup for thalassemia (a genetic disorder affecting hemoglobin production)?

From the Guidelines

The workup for thalassemia should begin with a complete blood count (CBC) with peripheral smear, followed by hemoglobin electrophoresis to identify abnormal hemoglobin patterns, and genetic testing for definitive diagnosis, including DNA analysis for common deletions and mutations in alpha and beta globin genes 1.

Initial Evaluation

The initial evaluation of thalassemia should include:

• A complete blood count (CBC) with peripheral smear to identify microcytic hypochromic anemia with normal or elevated red blood cell count
• Hemoglobin electrophoresis to identify abnormal hemoglobin patterns, with beta thalassemia showing elevated HbA2 (>3.5%) and HbF levels, while alpha thalassemia may show normal electrophoresis results
• Iron studies to exclude iron deficiency, as thalassemia patients typically have normal or elevated ferritin and serum iron levels

Definitive Diagnosis

Genetic testing is recommended for definitive diagnosis, including DNA analysis for common deletions and mutations in alpha and beta globin genes 1.

Additional Tests

Additional tests may include:

• Serum ferritin to assess iron overload
• Liver function tests
• Imaging studies like MRI for iron quantification in the liver and heart, particularly in severe cases or when cardiac iron overload is suspected 1

Family Screening and Genetic Counseling

Family screening is important since thalassemia is inherited in an autosomal recessive pattern. For pregnant women or couples planning pregnancy with family history of thalassemia, genetic counseling and prenatal testing should be considered to assess the risk of having a child with severe thalassemia.

Management

The management of thalassemia major, particularly in relation to cardiac iron overload, involves careful monitoring of cardiac function and iron levels, with treatment aimed at reducing iron overload and preventing cardiac complications 1.

From the Research

Thalassemia Workup

Thalassemia is a genetic disorder that affects the production of hemoglobin, a protein in red blood cells that carries oxygen to the body's tissues. The workup for thalassemia typically involves a combination of laboratory tests and physical examinations.

• Laboratory Tests:
  • Complete Blood Count (CBC) to evaluate red blood cell indices such as Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) 2
  • Serum iron levels to assess for iron overload or deficiency 2
  • Hemoglobin electrophoresis to separate and identify different types of hemoglobin 2, 3, 4
  • Molecular genetic testing, such as PCR and sequencing, to detect specific genetic mutations associated with thalassemia 3, 4
• Diagnostic Approach:
  • A stepwise algorithmic approach starting with clinical history, hematologic evaluation, protein-based analytic methods, and nucleic acid-based methods 4
  • Family studies may be helpful in certain cases 4
• Special Confirmatory Tests:
  • Determination of p50, Heinz body prep, and isopropanol or heat stability tests may be useful when an abnormality of hemoglobin function or stability is suspected 4

Note that the study 5 is not relevant to the workup for thalassemia.