From the Guidelines
Screening for sickle cell disease can be performed using a combination of methods, including a rapid sickle solubility test followed by a full haemoglobinopathy screen using high performance liquid chromatography, capillary electrophoresis, mass spectrometry, or gel electrophoresis, as recommended by the Association of Anaesthetists in 2021 1. The most effective approach to screening for sickle cell disease involves a step-wise process, starting with a rapid test to detect the presence of HbS, and if positive, proceeding to a more comprehensive haemoglobinopathy screen.
- The rapid sickle solubility test is a useful initial screening tool, but it should not be used in isolation as it cannot differentiate between heterozygous, compound heterozygous, or homozygous states, and may yield false negative results in certain cases, such as in neonates or heavily transfused patients 1.
- A full haemoglobinopathy screen, on the other hand, is highly sensitive, reliable, and reproducible, and can detect individuals who are homozygous or heterozygous for HbS or other haemoglobinopathies 1.
- Newborn screening programs, such as the NHS Sickle Cell and Thalassaemia Screening Programme, have been established in several countries to detect sickle cell disease early in life, allowing for prompt initiation of preventive measures and management 1.
- Other screening methods, such as hemoglobin electrophoresis, isoelectric focusing, and DNA analysis, may also be used in certain contexts, but the combination of a rapid sickle solubility test and a full haemoglobinopathy screen is a widely accepted and effective approach to screening for sickle cell disease 1.
From the Research
Methods for Screening Sickle Cell Disease
Several methods can be used to screen for sickle cell disease, including:
- High-performance liquid chromatography (HPLC) systems, such as the Variant NBS HPLC system and the Variant II system 2
- Isoelectric focusing (IEF) 3, 4
- Capillary electrophoresis (CE) 3
- Cation-exchange HPLC 5, 6
- Cellulose acetate electrophoresis at alkaline pH 4
- Solubility test or an electrophoresis on agar gel for confirmation of HbS 4
Advantages of Each Method
- HPLC systems are highly sensitive and specific, and can detect various hemoglobinopathies, including sickle cell disease 2, 5, 6
- IEF is a classical laboratory method that can detect SCD and other hemoglobinopathies 3
- CE is a rapid and accurate method for detecting hemoglobin variants 3
- Cation-exchange HPLC is suitable for routine investigation of hemoglobinopathies, with superior resolution and rapid assay time 6
Considerations for Screening
- The choice of screening method may depend on the resources available and the specific population being screened 5
- Confirmation of HbS should always be done by a specific test, such as the solubility test or an electrophoresis on agar gel 4
- Molecular analysis may be necessary to determine the cause of the disease in heterozygous subjects presenting with pathological manifestations 4