What test is needed to diagnose Sickle Cell Disease (SCD)?

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From the Guidelines

To test for sickle cell anemia, a hemoglobin electrophoresis test is needed, as it is the definitive diagnostic test that identifies the abnormal hemoglobin S protein responsible for the disease. This test is highly sensitive, reliable, and reproducible, and detects those who are homozygous or heterozygous for HbS or other haemoglobinopathies 1. The process typically begins with a complete blood count (CBC) and blood smear to look for anemia and abnormally shaped red blood cells, followed by the hemoglobin electrophoresis to confirm the diagnosis. For newborns, many countries include sickle cell screening in routine newborn testing using a blood sample from a heel prick. A simpler screening test called the sickle solubility test or Sickledex may be used initially, but positive results must be confirmed with hemoglobin electrophoresis, as it does not differentiate between heterozygous, compound heterozygous or homozygous states, and can give false negative results in neonates or in a heavily transfused patient 1.

Some key points to consider when testing for sickle cell anemia include:

  • The NHS sickle cell and thalassaemia screening programme was established in 2001, and all patients at risk of haemoglobinopathy should be screened for haemoglobinopathies before surgery, unless they are ethnically of solely northern or eastern European, Jewish or South-East Asian heritage, or have been screened previously 1.
  • Hospital laboratories use their own local algorithm for screening, which may include a rapid sickle solubility test followed by a full haemoglobinopathy screen using high performance liquid chromatography, capillary electrophoresis, mass spectrometry or gel electrophoresis 1.
  • Genetic testing can also identify the specific mutation in the beta-globin gene, and is an important tool in the diagnosis and management of sickle cell disease 1.
  • Early diagnosis allows for preventive care, including penicillin prophylaxis in children, appropriate vaccinations, and education about avoiding triggers that can cause painful sickle cell crises 1.

From the Research

Tests for Sickle Cell Anemia

To test for sickle cell anemia, several methods can be employed, including:

  • Hemoglobin electrophoresis, which is a useful tool in diagnosing sickle cell anemia and can be used to distinguish between different types of hemoglobinopathies 2, 3
  • DNA analysis, which can be used for prenatal diagnosis of sickle cell anemia using techniques such as Southern blot and polymerase chain reaction (PCR) 2
  • Screening tests, such as complete blood count, peripheral blood smears, and sickling test, which can help identify individuals with sickle cell disease 4
  • Confirmatory tests, such as hemoglobin separation techniques, which can provide a definitive diagnosis of sickle cell anemia 4, 5
  • Genetic tests, which can be used to identify carriers of the sickle cell gene and provide a definitive diagnosis of sickle cell anemia 4, 5
  • Solubility tests, which can be used to detect the presence of hemoglobin S, the abnormal hemoglobin that causes sickle cell anemia 5
  • Cation exchange HPLC, which can be used to separate and identify different types of hemoglobin, including hemoglobin S 5
  • Isoelectric focusing, which can be used to separate and identify different types of hemoglobin, including hemoglobin S 5
  • Cellulose acetate electrophoresis, which can be used to separate and identify different types of hemoglobin, including hemoglobin S 5

Choosing the Right Test

The choice of test will depend on the individual's clinical presentation, medical history, and the availability of testing facilities. In some cases, a combination of tests may be necessary to provide a definitive diagnosis of sickle cell anemia 4, 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Diagnosis and screening of sickle cell disease].

La Revue du praticien, 2004

Research

Utility of hemoglobin electrophoresis to distinguish between severe delayed hemolytic transfusion reaction versus hyperhemolysis syndrome.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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