Why is hemoglobin (Hb) electrophoresis not helpful in identifying alpha (α) thalassemia?

From the Guidelines

Hemoglobin electrophoresis is not a reliable method for identifying alpha thalassemia because it cannot detect the absence or reduction of alpha globin chains, which is the primary defect in this condition. This limitation is due to the fact that alpha thalassemia results from deletions or mutations in the alpha globin genes, leading to a reduction or elimination of alpha chain production, without creating abnormal hemoglobin variants that would be visible on electrophoresis 1. The normal ratio of hemoglobin types in alpha thalassemia means that the electrophoresis pattern appears essentially normal, making it an ineffective tool for diagnosis.

In contrast to beta thalassemia, where electrophoresis can reveal distinctive patterns due to increased HbA2 and HbF, alpha thalassemia requires molecular genetic testing to detect specific gene deletions or mutations, along with complete blood count findings and family studies, for accurate diagnosis. Key points to consider in the diagnosis of alpha thalassemia include:

• The importance of molecular genetic testing for detecting specific gene deletions or mutations
• The role of complete blood count findings, such as microcytic, hypochromic anemia
• The value of family studies in identifying carriers and affected individuals
• The limitations of hemoglobin electrophoresis in detecting alpha thalassemia, as highlighted in the context of nonimmune hydrops fetalis, where alpha thalassemia is a significant cause 1.

It is crucial to prioritize these diagnostic approaches over hemoglobin electrophoresis for the accurate identification of alpha thalassemia, given its implications for morbidity, mortality, and quality of life, particularly in populations where this condition is prevalent, such as Southeast Asian populations, where it accounts for a significant percentage of nonimmune hydrops fetalis cases 1.

From the Research

Limitations of Hemoglobin Electrophoresis in Alpha Thalassemia Diagnosis

• Hemoglobin electrophoresis is a diagnostic tool used to identify abnormal hemoglobin variants, but it has limitations in detecting alpha thalassemia 2.
• Alpha thalassemia is characterized by the deletion or mutation of one or more of the four alpha-globin genes, which can lead to reduced or absent production of alpha-globin chains 2.
• Hemoglobin electrophoresis may not be able to detect the absence or reduction of alpha-globin chains, making it less useful for diagnosing alpha thalassemia 2.

Importance of Genetic Testing in Alpha Thalassemia Diagnosis

• Genetic testing is required to confirm the diagnosis of alpha thalassemia, as it can detect the specific genetic mutations or deletions responsible for the condition 2.
• Genetic testing can identify the presence of alpha thalassemia trait or carrier state, which can be important for family planning and genetic counseling 2.
• The presence of alpha thalassemia can influence the clinical outcome of other hemoglobinopathies, such as sickle cell disease, and genetic testing can help identify individuals at risk 3, 4, 5.

Clinical Implications of Alpha Thalassemia

• Alpha thalassemia can have a protective effect against certain complications of sickle cell disease, such as stroke and cholelithiasis 5.
• The presence of alpha thalassemia can influence the clinical outcome of transfusion-dependent beta-thalassemia, and genetic testing can help identify individuals at risk 6.
• Alpha thalassemia can also have implications for the management of other hemoglobinopathies, and genetic testing can help guide treatment decisions 2, 3, 4, 5, 6.