Sickle cell disease is diagnosed through a blood test that separates and measures the different types of hemoglobin in your blood. In the United States, every newborn is screened for sickle cell at birth, so most people are diagnosed within the first few days of life. For those who weren’t screened or need testing later, the same blood-based methods can confirm a diagnosis at any age.
Newborn Screening
Every state in the U.S. mandates newborn screening for sickle cell disease. A few drops of blood are taken from your baby’s heel shortly after birth, and the sample is sent to a lab for analysis. This routine screening catches the disease before symptoms appear, which matters because early treatment significantly reduces complications in the first years of life.
If the newborn screen comes back positive, a second confirmatory test is performed. A positive screen alone is not a final diagnosis. The confirmatory test uses a more precise method to verify the type and amount of abnormal hemoglobin present.
Hemoglobin Electrophoresis
The primary diagnostic test is hemoglobin electrophoresis. It works by applying an electric current to a blood sample, which separates the different types of hemoglobin based on their electrical charge. Each type can then be measured individually. In healthy adults, the dominant form is hemoglobin A (HbA). In sickle cell disease, the blood contains hemoglobin S (HbS), the abnormal form that causes red blood cells to stiffen into a crescent shape.
The percentages of each hemoglobin type tell the story. A person with sickle cell trait (a carrier who inherited one sickle gene and one normal gene) typically has 50 to 60% HbA and 35 to 45% HbS. A person with sickle cell disease has little to no HbA, with HbS making up the majority of their hemoglobin. This distinction between trait and disease is one of the most important things the test reveals, since sickle cell trait rarely causes symptoms while the disease requires lifelong management.
Confirmatory Testing With HPLC
Many labs use a second method called high-performance liquid chromatography (HPLC) to confirm what the initial electrophoresis found. HPLC can detect more types of hemoglobin than standard gel electrophoresis and provides precise measurements of each one. It’s particularly useful for quantifying HbS and fetal hemoglobin (HbF) levels, which becomes important for monitoring treatment over time.
Using two different methods reduces the chance of a misidentification. Some abnormal hemoglobin types can look similar on one test but behave differently on another, so running both provides a more reliable picture.
Why Solubility Tests Aren’t Enough
You may encounter a quick screening method called a sickle solubility test (sometimes known by the brand name Sickledex). This test detects the presence of hemoglobin S but has important limitations. It cannot distinguish between sickle cell trait and sickle cell disease, and it misses non-S hemoglobin variants like hemoglobin C, which can also combine with HbS to cause disease.
Solubility tests also produce false negatives in people with severe anemia, those with HbS levels below 10%, or infants with high levels of fetal hemoglobin. Because newborns naturally have elevated fetal hemoglobin, solubility testing is unreliable in the first months of life. A solubility test alone is not considered sufficient to confirm or rule out sickle cell disease or trait.
Genetic Testing
DNA-based testing looks directly at the hemoglobin beta (HBB) gene for the specific mutation that causes sickle cell. This approach is used when blood-based hemoglobin tests produce ambiguous results, or when doctors need to identify the exact genetic variant involved. Full sequencing of the HBB gene can also detect other mutations like beta thalassemia and hemoglobin C variants, which is helpful for understanding a person’s complete hemoglobin profile.
Genetic testing is especially valuable for family planning. If both parents carry sickle cell trait, each pregnancy has a 25% chance of producing a child with sickle cell disease. Knowing the precise genetic status of each parent helps couples understand their risk.
Prenatal Diagnosis
Sickle cell disease can be diagnosed before birth, as early as 8 to 10 weeks into pregnancy. Prenatal testing looks for the sickle cell gene rather than the abnormal hemoglobin itself, since the fetus hasn’t yet produced enough hemoglobin to measure directly.
Two procedures can provide the sample. One collects a small piece of tissue from the placenta (the organ connecting the umbilical cord to the uterus). The other draws a sample of the amniotic fluid surrounding the developing baby. Both carry a small risk of complications, so they’re typically offered when both parents are known carriers or when there’s a family history of the disease.
Rapid Point-of-Care Tests
Newer rapid diagnostic kits are designed for use in clinics and resource-limited settings where lab equipment isn’t readily available. These tests use a small blood sample and produce results in minutes. One such test, SICKLECHECK, demonstrated sensitivity above 97% and specificity above 98% for detecting both sickle cell trait and disease when compared against HPLC results. Several similar products exist, including HemoTypeSC and SickleSCAN.
These rapid tests are useful for initial screening, particularly in regions with high sickle cell prevalence and limited laboratory infrastructure. However, a positive rapid test result still needs confirmation through standard electrophoresis or HPLC before a formal diagnosis is made.
Symptoms That Prompt Testing
When sickle cell disease isn’t caught through newborn screening, certain early symptoms often lead a doctor to order testing. In infants and young children, the most common signs include yellowing of the skin or eyes (caused by red blood cells breaking down faster than normal), unusual tiredness or irritability from anemia, and painful swelling of the hands and feet, a condition called dactylitis that results from sickle-shaped cells blocking small blood vessels.
In older children and adults who were never screened, recurrent episodes of severe pain, unexplained anemia, or frequent infections can prompt a doctor to check hemoglobin levels. Anyone with a family history of sickle cell disease or trait who hasn’t been tested can request hemoglobin electrophoresis through a simple blood draw. The test requires no special preparation and results are typically available within a few days.