Sickle cell disease is detected through a simple blood test that identifies abnormal hemoglobin in red blood cells. In the United States and many other countries, every newborn is screened automatically within the first few days of life using a heel prick blood sample. For older children and adults who were never screened, a standard blood draw can provide the same answers.
Newborn Screening
Most people with sickle cell disease are identified at birth, before symptoms ever appear. A few drops of blood are collected from the baby’s heel, applied to a special filter paper, and sent to a lab. This typically happens within the first two to three days of life. The lab analyzes the sample for abnormal types of hemoglobin, the oxygen-carrying protein inside red blood cells.
In healthy newborns, the predominant hemoglobin is fetal hemoglobin (HbF), with small amounts of normal adult hemoglobin (HbA) starting to appear. A baby with sickle cell disease will show sickle hemoglobin (HbS) and no HbA at all. A baby who carries the trait but doesn’t have the disease will show both HbA and HbS. If the screen comes back positive or unclear, a confirmatory test is performed to pin down exactly which type of hemoglobin variant is present and in what amounts.
Blood Tests for Older Children and Adults
If you weren’t screened at birth, or if you need to confirm your status, a doctor can order a hemoglobin analysis from a routine blood draw. No fasting or special preparation is needed. The one important caveat: if you’ve had a blood transfusion within the past 90 days, the results may be inaccurate. Transfused blood dilutes the sickle hemoglobin in your sample, potentially masking the disease.
There are several lab methods used to analyze the blood, and they differ in precision.
Hemoglobin Electrophoresis
This is the traditional method. It separates hemoglobin types by running them through an electric field, where different hemoglobin variants move at different speeds. The lab can then see which types are present and roughly how much of each one you have. Electrophoresis works well for common variants but struggles with some rarer ones. It can’t always tell the difference between certain hemoglobin types that move at the same speed, and it’s less accurate at measuring low concentrations.
High-Performance Liquid Chromatography (HPLC)
HPLC is increasingly the preferred method, especially for screening programs. It separates hemoglobin types based on how they interact with a liquid flowing through a column, assigning each variant a characteristic detection time. The advantage over electrophoresis is that HPLC can identify and measure multiple hemoglobin types in a single test with high precision. It’s faster, requires less hands-on labor, and is more reliable at quantifying small but important fractions like HbA2 and HbF, which help distinguish between different forms of sickle cell disease.
The Solubility Test (Sickledex)
You may encounter a quick screening test called the solubility test or sickle prep. This test detects the presence of sickle hemoglobin by mixing your blood with a chemical solution. If HbS is present, the solution turns cloudy. It’s cheap and fast, but it has serious limitations. It cannot tell the difference between sickle cell disease and sickle cell trait. It misses some compound forms of the disease, like HbSC. High levels of fetal hemoglobin in infants can cause false negatives. And false positives have been reported. A solubility test alone is never sufficient to confirm or rule out sickle cell disease or trait. Any positive or unclear result needs to be followed up with electrophoresis or HPLC.
What Results Look Like
The confirmatory test doesn’t just say “positive” or “negative.” It tells you which hemoglobin types are in your blood and what percentage each one makes up. This matters because sickle cell disease isn’t a single condition. It’s a group of related disorders, and the specific combination of hemoglobin variants you carry determines severity.
In the most common form, sickle cell anemia (HbSS), the blood typically shows about 80% sickle hemoglobin, 1% to 20% fetal hemoglobin, 2% to 4.5% HbA2, and no normal adult hemoglobin at all. Red blood cells under the microscope appear normal in size, with visible sickle-shaped cells, target cells, and other characteristic changes.
A related form called S/beta-zero thalassemia looks similar on electrophoresis, with 75% to 90% sickle hemoglobin and no HbA. But the red blood cells themselves are smaller and paler than in HbSS, and the HbA2 level tends to be higher (4% to 6%, sometimes more). These subtle differences are what the lab uses to tell the two apart.
In HbSC disease, another common variant, the blood shows both sickle hemoglobin and hemoglobin C. In sickle cell trait (carrying one copy of the gene without having the disease), you’ll see both normal HbA and HbS, with HbS typically making up less than 41% of the total.
When Genetic Testing Is Used
Most of the time, protein-based blood tests like HPLC and electrophoresis are all you need. But in certain situations, DNA testing provides a definitive answer. Genetic testing looks directly at the hemoglobin beta gene (HBB) for the specific mutation that causes sickle hemoglobin.
This is most useful when blood test results are ambiguous, when you need to determine the exact genetic combination for family planning purposes, or when distinguishing between variants that look similar on standard lab tests. Full sequencing of the HBB gene can also detect beta thalassemia mutations and hemoglobin C, which is important because inheriting one sickle gene alongside one of these other variants can still cause sickle cell disease.
Prenatal Testing
If both parents carry the sickle cell gene (or a related variant), testing can be done during pregnancy to determine whether the baby is affected. Chorionic villus sampling, which takes a tiny tissue sample from the placenta, can be performed between 8 and 12 weeks of pregnancy. Amniocentesis, which collects a small amount of fluid surrounding the baby, is available at around 16 weeks. Both tests provide fetal DNA that can be analyzed for the sickle cell mutation.
Some programs also screen pregnant women earlier in the process. In one well-known approach, women are tested before 28 weeks of pregnancy. Those who carry sickle hemoglobin or hemoglobin C are counseled about the implications and encouraged to have their babies tested after birth.
How Long Results Take
Turnaround time depends on the type of test and how it’s ordered. A hemoglobin electrophoresis or HPLC run at a hospital lab often comes back within a few days to two weeks. If you’re requesting archived newborn screening results from a state health department, the process can take up to 30 days. If you need answers faster, asking your doctor to order a fresh blood test is the quicker route.
For newborn screening, most states notify families within one to two weeks if additional testing is needed. A positive newborn screen is typically followed by a confirmatory test using HPLC or electrophoresis, and families are referred to a specialist who manages sickle cell disease for ongoing care.