Sickle cell disease is diagnosed through a blood test that identifies abnormal hemoglobin in your red blood cells. In the United States, every newborn is screened for it at birth as part of mandatory testing. For older children and adults, the same core lab techniques apply, and results typically come back within a few days.
Newborn Screening at Birth
All 50 U.S. states require universal newborn screening for sickle cell disease. Within 24 to 48 hours of birth, a healthcare provider pricks your baby’s heel and collects a few drops of blood on a special card. That sample is sent to a lab where the hemoglobin is analyzed to identify which types are present. The screening catches both sickle cell disease and sickle cell trait, meaning it will tell you if your baby is a carrier of the gene even if they don’t have the disease itself.
The lab methods used on newborn samples are protein-based tests that separate hemoglobin by its physical or chemical properties. The three most common are high-performance liquid chromatography (HPLC), capillary electrophoresis, and isoelectric focusing. Each one can distinguish normal hemoglobin from sickle hemoglobin and other variants in a single run.
One older method, the sickle solubility test, is not used for newborns. Babies are born with high levels of fetal hemoglobin, which produces false-negative results on solubility testing. That test also cannot tell the difference between sickle cell trait and sickle cell disease, making it unreliable as a standalone diagnostic tool at any age.
How the Main Lab Tests Work
Hemoglobin electrophoresis is the traditional method. It works by placing a blood sample in an electric field, which causes different hemoglobin types to migrate at different speeds. The lab can then see which types are present and roughly how much of each one you have. The limitation is that electrophoresis is slow, labor-intensive, and struggles to accurately measure hemoglobin variants that are present in very small amounts.
HPLC has become the preferred initial screening method in many labs. It separates hemoglobin types based on how they interact with a column of charged material, and each variant passes through in a characteristic time window. HPLC is faster, requires less hands-on work, and is more precise, with a measurement variation of only about 1% between runs. It can quantify normal hemoglobin, sickle hemoglobin, fetal hemoglobin, and other variants all in one test. The tradeoff is that the presence of sickle hemoglobin can slightly skew the measurement of certain minor hemoglobin fractions, which sometimes means a second method is needed to confirm findings.
In practice, labs often use two complementary methods. If the first test flags a possible hemoglobin variant, a second technique confirms it. When both agree, the diagnosis is highly reliable. Studies using these combined approaches have shown 100% sensitivity and specificity for identifying sickle cell disease, sickle cell trait, and other common variants.
What the Results Mean
Your results will show the percentage of each hemoglobin type in your blood. Normal adult hemoglobin is called hemoglobin A. Sickle hemoglobin is called hemoglobin S. The ratio between these two tells the story.
If you have sickle cell trait (one copy of the gene), your hemoglobin A to S ratio is typically around 60:40. You carry the gene but generally don’t experience symptoms. Normal hemoglobin A is dominant because the protein building blocks in your red blood cells have a stronger preference for it.
Sickle cell disease looks very different on the results. People with the most severe form (called HbSS) have over 90% sickle hemoglobin and 0% hemoglobin A. Other forms of sickle cell disease exist depending on which combination of gene variants you inherited:
- HbSC disease: Roughly 50% hemoglobin S and 50% hemoglobin C, with mild to moderate symptoms.
- S beta-plus thalassemia: Over 60% hemoglobin S with 10 to 30% hemoglobin A still present. Typically mild to moderate.
- S beta-zero thalassemia: Over 80% hemoglobin S with 0% hemoglobin A. Moderate to severe, similar in presentation to HbSS.
Your provider interprets these percentages alongside a complete blood count that includes hemoglobin level and red blood cell size. Together, this information pinpoints the specific type of sickle cell disease.
Genetic (DNA) Testing
Protein-based tests like HPLC and electrophoresis identify what hemoglobin your body is making. DNA testing goes a step further by identifying the exact mutation in the hemoglobin gene responsible. This is considered the definitive confirmation.
Genetic testing becomes especially important in a few scenarios. In infants under one year old, high levels of fetal hemoglobin can mask the signs of certain hemoglobin disorders on protein-based tests, potentially leading to a false-negative result. DNA testing eliminates that risk. It’s also used when protein-based results are ambiguous, for example when a hemoglobin variant has an unusual pattern that could represent more than one condition. If standard screening comes back normal but blood counts still look abnormal, the next step is sequencing the hemoglobin gene to look for rarer mutations that wouldn’t show up on routine panels.
Testing Before Birth
If both parents carry the sickle cell gene, prenatal testing can determine whether the baby has inherited sickle cell disease. Two procedures are used, depending on how far along the pregnancy is.
Chorionic villus sampling (CVS) is performed between weeks 10 and 13 of pregnancy. A small sample of tissue from the placenta is collected and analyzed for the sickle cell mutation using DNA testing. Amniocentesis is the alternative, done around week 16, using a sample of the fluid surrounding the baby. Both tests are diagnostic, not just screening tools, so they give a definitive yes-or-no answer about whether the baby has sickle cell disease. CVS offers the advantage of earlier results, giving parents more time to prepare.
Testing for Adults Who Missed Screening
Not everyone was screened at birth. Universal newborn screening wasn’t adopted in all U.S. states until the early 2000s, and many people born outside the U.S. were never screened at all. In some cases, sickle cell disease goes undiagnosed well into adulthood. One documented case in Nigeria involved a patient diagnosed at age 52.
Adults typically come to testing after recurring symptoms that don’t have an obvious explanation: episodes of intense joint or bone pain (often in the knees, lower back, and elbows), chronic anemia, or fatigue that comes in waves. A 22-year-old patient described in the medical literature, for instance, had six months of recurring joint pain scoring 7 out of 10 in severity before the diagnosis was finally made. For adults, the same blood tests used in newborn screening apply. A hemoglobin electrophoresis or HPLC test on a standard blood draw will identify the presence of sickle hemoglobin and its percentage, followed by DNA testing if confirmation is needed.
Rapid Tests for Low-Resource Settings
In parts of the world where lab equipment isn’t readily available, rapid point-of-care tests can screen for sickle cell disease using just a finger prick and a small test strip. These work similarly to a home pregnancy test: antibodies on the strip react with specific hemoglobin types in your blood, producing visible lines that indicate which variants are present.
The two most widely validated rapid tests are HemoTypeSC and SickleSCAN, both of which can detect hemoglobin A, S, and C. A newer option called SickleCheck uses the same core technology but can also flag the presence of other, less common hemoglobin variants. These tests don’t require electricity, specialized equipment, or trained lab staff, making them practical for remote clinics. They’re used as screening tools rather than final diagnoses. A positive result still needs confirmation with a lab-based method, but rapid tests dramatically reduce the number of people who go undiagnosed simply because they don’t have access to a hospital laboratory.