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Sickle Cell Screen

Test code(s) 825(X)

Question 1. Is sickle cell trait the same as sickle cell anemia?

No. People with sickle cell anemia (Hgb S/S) have the hemoglobin S gene mutation on both of their beta globin genes, whereas people with sickle cell trait (Hgb A/S) have the mutation on only one beta globin gene. People with sickle cell trait are considered carriers and are usually asymptomatic. However, sickle cell formation leading to vascular occlusion can occur during high fever and under conditions of significant hypoxia. Differentiating sickle cell anemia from the trait is important for clinical management and genetic counseling of the individual.

Question 2. Is sickle cell anemia the same as sickle cell disease?

No. Sickle cell disease refers to any condition that causes a sickling disorder. Sicklecell anemia is one type of sickle cell disease. It is caused by the presence of a Hgb S on both beta globin genes. Other types of sickle cell disease are caused by presence of Hgb S on one beta globin gene and Hgb C, Hgb D-Punjab (D-Los Angeles), Hgb O-Arab, Hgb C-Harlem, Hgb Lepore, or beta thalassemia on the other beta globin gene.

Question 3. What is a sickle cell solubility test?

The sickle cell solubility test is a qualitative test based on the relative insolubility of hemoglobin S compared to other hemoglobin variants. A positive test indicates the presence of hemoglobin S or a non-S sickling hemoglobin. Results should be confirmed by high-performance liquid chromatography (HPLC) (Hemoglobinopathy Evaluation, test code 35489[X]).1

Question 4. Does a positive sickle cell solubility test mean that a patient has sickle cell disease?

A positive test is consistent with sickle cell trait, sickle cell anemia and hemoglobin S in combination with another hemoglobin variant, e.g. hemoglobin C-Harlem. Positive results can also occur with other sickling hemoglobins like Hgb S Travis, Hgb C Ziguinchor as well as with high concentrations of Hgb Bart’s. A false positive result can also be seen in cryoglobulinemia and certain medical conditions, e.g., polycythemia and hypergammaglobulinemia (e.g. multiple myeloma), when nucleated red blood cells are present in the peripheral blood.

Question 5. What are the limitations of the sickle cell solubility test?

  • False-negative results can be obtained if there has been a recent transfusion, if the percentage of hemoglobin S is below 15% to 20%, if the concentration of fetal hemoglobin (Hgb F) is high and if there is severe anemia with the total hemoglobin <8 g/dL. This test is contraindicated for newborns up to 6 months of age owing to the high concentration of Hgb F.
  • False-positive results can be obtained if nucleated red blood cells are present in the peripheral blood, the patient has marked hypergammaglobulinemia (e.g. in multiple myeloma), there are sickling hemoglobins other than hemoglobin S and certain medical conditions (see above).
  • This test does not differentiate sickle cell trait from sickle cell anemia nor is it intended as a screen for other significant hemoglobin variants that combine with hemoglobin S, e.g. hemoglobin C and hemoglobin D.



  1. Martin HS, Bernard GF, et al. Disorders of hemoglobin. Genetics, Pathophysiology, and Clinical Management. 2nd edition. New York, NY: Cambridge University Press; 2009:549. 
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on his/her education, clinical expertise, and assessment of the patient.
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