What are the diagnostic tests for hemoglobinopathies (hemoglobin disorders)?

From the Guidelines

Testing for hemoglobinopathies should start with a complete blood count (CBC) and hemoglobin electrophoresis as first-line tests, followed by additional tests such as high-performance liquid chromatography (HPLC) or capillary electrophoresis if necessary, as recommended by the most recent guidelines 1. When testing for hemoglobinopathies, it is essential to consider the patient's clinical history, family history, and the time of last blood transfusion, as well as their ethnic background, to determine the risk of hemoglobinopathies 1. Some key points to consider when testing for hemoglobinopathies include:

• The use of a rapid sickle solubility test to detect the presence of HbS, followed by a full haemoglobinopathy screen using HPLC, capillary electrophoresis, mass spectrometry, or gel electrophoresis if positive 1
• The importance of avoiding repeated unnecessary screening, especially in patients who have been previously screened or are from low-risk ethnic backgrounds 1
• The need to consider recent blood transfusions, iron status, and alpha-thalassemia silent carriers when interpreting test results 1
• The use of newborn screening programs, such as the NHS sickle cell and thalassaemia screening programme, to detect hemoglobinopathies in newborns 1 Overall, a stepwise approach to testing for hemoglobinopathies, taking into account the patient's individual risk factors and medical history, is essential for accurate diagnosis and effective management of these conditions.

From the Research

Testing for Hemoglobinopathies

• Hemoglobinopathies are genetic disorders that lead to abnormal structure of the hemoglobin molecule, and can be diagnosed through a stepwise algorithmic approach, starting with a detailed clinical history, hematologic evaluation, protein-based analytic methods, and nucleic acid-based methods 2.
• The diagnosis of hemoglobinopathies can be achieved through various methods, including hemoglobin electrophoresis, isoelectric focusing, cation exchange high performance liquid chromatography (HPLC), and reversed phase HPLC 2, 3.
• High-performance liquid chromatographic methods have been developed for either screening or confirmation of hemoglobinopathies with relatively high sensitivity or specificity, and can separate more than 45 commonly encountered hemoglobin variants within 12 min 3.
• Blood transfusions are a mainstay of therapy for certain hemoglobinopathies, such as sickle cell disease and beta thalassemia major, although stem cell transplantation is a potentially curative option 4, 5.
• The clinical manifestations of hemoglobinopathies can range from mild hypochromic anemia to moderate hematological disease to severe, lifelong, transfusion-dependent anemia with multiorgan involvement, and require a wide variety of diagnostic and therapeutic measures 5.

Diagnostic Methods

• Hemoglobin electrophoresis is a widely utilized method for hemoglobin analysis, but has limited resolution and can sometimes result in incorrect or unresolved diagnosis of common hemoglobinopathies 3.
• Isoelectric focusing provides excellent resolution but is labor intensive and lacks accurate quantitation, while HPLC methods can provide accurate quantitation of hemoglobin concentration, particularly Hb F and A2, which are useful for the diagnosis of HPFH and beta-thalassemia, respectively 3.
• Family studies can also be helpful in certain cases, and special confirmatory tests, such as determination of p50, Heinz body prep, and isopropanol or heat stability tests, can be useful when an abnormality of Hb function or stability is suspected from the phenotype 2.

Treatment Options

• Blood transfusions are a mainstay of therapy for certain hemoglobinopathies, such as sickle cell disease and beta thalassemia major, and can help to alleviate symptoms and prevent complications 4, 5.
• Stem cell transplantation is a potentially curative option for severe forms of thalassemia, and supportive treatment, such as periodic blood transfusions and iron chelation, can help to manage the disease and improve quality of life 5.
• Drugs to treat the symptoms of sickle-cell disease, such as analgesics, antibiotics, ACE inhibitors, and hydroxyurea, can also be effective in managing the disease 5.