Blood Test to Screen for Sickle Cell Disease
Newborn screening for hemoglobinopathy using high-performance liquid chromatography (HPLC), capillary electrophoresis, mass spectrometry, or gel electrophoresis is the recommended blood test to screen for sickle cell disease, with universal screening mandated in all 50 U.S. states, the District of Columbia, Puerto Rico, the U.S. Virgin Islands, and the U.S. military, achieving 99.5-100% sensitivity and specificity. 1, 2
Newborn Screening (Birth to 3 Months)
Universal newborn screening is performed on all infants using dried blood spot samples collected within the first few days of life, typically by day 5 for optimal specificity 1, 2, 3
The screening definitively diagnoses sickle cell disease at birth before symptoms develop, as infants are healthy initially due to protective fetal hemoglobin levels 1
Results must be documented in the medical record and discussed with families at diagnosis, with re-discussion recommended at school entry, preadolescence, and transition to adult care 1, 2
Infants with positive screening should be referred to a pediatric SCD center or hematologist before 3 months of age for comprehensive care management 1
Confirmatory Testing
Hemoglobin electrophoresis is the gold standard confirmatory test that separates and identifies different hemoglobin types (HbA, HbS, HbC, HbF) and distinguishes between sickle cell trait (HbAS: 55-65% HbA, 30-40% HbS) and sickle cell disease variants (HbSS, HbSC, HbS-β-thalassemia) 2, 4
A second confirmatory test is required using either solubility testing or electrophoresis on agar in citrate buffer to validate the initial screening result 4, 5
Isoelectric focusing provides superior resolution compared to conventional cellulose acetate electrophoresis at alkaline pH 5
Cation exchange HPLC is an acceptable first-line test in laboratories equipped with this technology 5
Testing for Individuals Without Prior Newborn Screening
For individuals born outside the U.S., immigrants, or those born before 1987 (when routine screening began), order hemoglobin electrophoresis directly as the initial comprehensive test 2, 4
Do not assume negative screening in these populations as they may never have been tested 2
Extended red cell antigen profiling by genotype or serology should be obtained at the earliest opportunity, optimally before the first transfusion, including at minimum K, Jk^a/Jk^b, Fy^a/Fy^b antigens 4
Special Populations
Pregnant Women and Family Screening
When sickle cell trait is identified in a pregnant woman, the baby's father must be tested to determine fetal risk, as there is a 25% chance of having a child with sickle cell disease if both parents carry the trait 2
Siblings of diagnosed children should be tested and results discussed at school entry, preadolescence, and transition visits 1
Adults and Adolescents
Hemoglobin electrophoresis is the appropriate test for adults or adolescents with unknown sickle cell status who present with suggestive symptoms 2, 4
Complete blood count with reticulocyte count should accompany diagnostic testing to assess for normocytic normochromic anemia and evaluate bone marrow response to hemolysis 6, 4
Point-of-Care Testing Options
Rapid lateral flow immunoassays (such as Sickle SCAN or HemoTypeSC) demonstrate 98-100% sensitivity and specificity for detecting HbA, HbS, and HbC, and are suitable for resource-limited settings or rapid screening 7, 8, 9
These devices work with both liquid blood and dried blood spots without loss of accuracy 7
Point-of-care tests are appropriate for initial screening but confirmatory testing with hemoglobin electrophoresis remains necessary for definitive diagnosis 8
Critical Pitfalls to Avoid
Never rely solely on solubility testing for definitive diagnosis, as it cannot differentiate between sickle cell trait (HbAS) and disease (HbSS, HbSC), and may give false negative results in neonates or heavily transfused patients 2, 4, 5
Do not use a positive sickle solubility test in isolation, as it doesn't distinguish between heterozygous, compound heterozygous, or homozygous states 4
Serologic phenotyping may be inaccurate if the patient has been transfused within the last 3 months, making genotyping the preferred method for extended red cell antigen profiling 4
High concentrations of HbF in newborns do not interfere with modern screening methods' ability to detect HbS or HbC, which can be accurately detected at concentrations as low as 1-2% 7