What blood test is used to determine sickle cell trait?

Blood Test for Sickle Cell Trait Detection

Hemoglobin electrophoresis is the definitive blood test for determining sickle cell trait, capable of identifying all hemoglobin variants including HbS. 1

Primary Diagnostic Methods

Newborn Screening (Birth)

• All 50 U.S. states, the District of Columbia, Puerto Rico, the U.S. Virgin Islands, and the U.S. military perform universal newborn screening for hemoglobinopathies that can make a definitive diagnosis of sickle cell trait at birth. 1
• This screening has been routine since 1987 following National Institutes of Health recommendations. 1
• Results should be documented in the medical record and discussed with families at diagnosis, school entry, preadolescence, and transition to adult care. 1

Hemoglobin Electrophoresis

• This is the gold standard confirmatory test that separates and identifies different hemoglobin types, including HbA, HbS, HbC, and HbF. 1, 2, 3
• Hemoglobin electrophoresis can distinguish between sickle cell trait (HbAS: 55-65% HbA, 30-40% HbS) and sickle cell disease variants. 1
• This method detects all abnormal hemoglobins beyond just hemoglobin S, making it essential when comprehensive genetic counseling is planned. 4

Alternative Screening Methods

Solubility Testing (Sickledex)

• Detects the presence of hemoglobin S with high reliability but cannot distinguish between sickle cell trait and sickle cell disease. 4
• This turbidity test is commonly used for rapid screening of blood donors before transfusion to specific patient populations. 5
• Major limitation: does not detect other abnormal hemoglobins (HbC, beta-thalassemia) and requires confirmatory hemoglobin electrophoresis for definitive diagnosis. 4

Point-of-Care Rapid Tests

• Newer technologies like Sickle SCAN and HemoTypeSC show 99.5-100% sensitivity and specificity compared to hemoglobin electrophoresis. 5, 6
• These tests cost approximately $2 per test and provide results rapidly, making them valuable in resource-limited settings. 6
• The dithionate-qualitative solubility point-of-care test showed 63.64% sensitivity but 100% specificity in field studies, indicating it may miss some cases. 7

Clinical Algorithm for Testing

For individuals without prior newborn screening (born outside the U.S., immigrants, or pre-1987 births):

• Order hemoglobin electrophoresis directly as the initial test. 1
• This provides comprehensive hemoglobin phenotype information in a single test. 3, 4

For rapid screening scenarios (blood donation, pre-operative):

• Solubility testing can be used for initial screening. 5
• Any positive solubility test must be confirmed with hemoglobin electrophoresis to distinguish trait from disease and identify other variants. 4

Important Clinical Considerations

Partner Testing

• When sickle cell trait is identified in a pregnant woman, the baby's father must also be tested to determine if the fetus is at risk for sickle cell disease. 1
• If both parents have sickle cell trait, there is a 25% chance with each pregnancy of having a child with sickle cell disease. 1

Impact on Other Laboratory Tests

• Sickle cell trait can lower A1C values by approximately 0.3% compared to individuals without the trait at the same glycemic level. 8
• Some A1C assay methods experience interference from hemoglobin S variant, affecting measurement accuracy. 8
• For diabetes monitoring in patients with sickle cell trait, use A1C assays unaffected by hemoglobin variants, or consider alternative markers like fasting plasma glucose or fructosamine. 8

Common Pitfalls to Avoid

• Never rely solely on solubility testing for definitive diagnosis - it cannot differentiate between trait (HbAS) and disease (HbSS, HbSC). 4
• Do not assume negative newborn screening in individuals born before 1987 or outside the U.S. - order confirmatory testing. 1
• Recognize that sickle cell trait is generally benign but can be associated with exercise-related complications, particularly exertional rhabdomyolysis in extreme conditions. 1
• Remember to test and counsel siblings of affected individuals, as they may also carry the trait. 1