The main sickle cell test names you’ll see on a lab request are the sickle solubility test (often sold as Sickledex), hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), isoelectric focusing, and DNA analysis of the HBB gene. The solubility test only shows whether hemoglobin S is present. Electrophoresis, HPLC, or DNA testing tells you whether that means sickle cell trait or sickle cell disease, and which type.
Lab reports and order forms often use different names for the same test. That confuses patients, and sometimes clinicians too. Below I translate the names, explain what each test can and can’t tell you, and show where each fits in care.
Why Sickle Cell Testing Uses Several Tests
Sickle cell disease is an inherited condition in which red cells contain hemoglobin S (HbS). This abnormal hemoglobin stiffens the cells when oxygen is low. It results from a change in the HBB gene on chromosome 11, a story told in our article on the origins of sickle cell disease. When two carrier parents each pass on the gene, each child has a 25% chance of having the disease.
No single test answers every question. Some are quick screens. Others separate and measure each type of hemoglobin. Genetic tests read the gene itself. For a broader walk-through of testing strategy, see our guide to sickle cell testing.
Sickle Cell Test Names at a Glance
| Test name (and common aliases) | What it detects | Main use | Key limitation |
|---|---|---|---|
| Sickle solubility test (Sickledex, “sickle screen”) | Presence of HbS | Quick screening | Cannot tell trait from disease; unreliable in young infants |
| Sodium metabisulfite sickling test (“sickle prep”) | Red cells that sickle when oxygen is removed | Simple screening where other tests are unavailable | Same limits as the solubility test |
| Hemoglobin electrophoresis (alkaline and acid) | Separates hemoglobins by electrical charge | Diagnosis and type | Some variants move to the same spot |
| HPLC (hemoglobinopathy screen) | Separates and measures each hemoglobin | Newborn screening, diagnosis, HbS percentage | Unusual variants need confirmation |
| Isoelectric focusing (IEF) | Separates hemoglobins by charge with high resolution | Newborn screening | Mainly a qualitative test |
| Capillary electrophoresis | Automated charge-based separation | Routine diagnosis in many labs | Unusual variants need confirmation |
| HBB gene testing (DNA analysis, sequencing) | The exact mutation(s) | Unclear cases, prenatal testing | Slower and more costly |
Screening Tests
Sickle Solubility Test
Blood is mixed with a chemical that removes oxygen. Deoxygenated HbS doesn’t dissolve, so the mixture turns cloudy. The test is fast and cheap. However, it gives the same positive result for sickle cell trait and sickle cell disease. It can also be falsely negative in babies under about 6 months, who still have mostly fetal hemoglobin, and in people with very low hemoglobin. A positive result always needs a follow-up test that separates the hemoglobins.
Newborn Screening
Many countries test a heel-prick blood spot from every newborn. The methods are usually HPLC or isoelectric focusing, with a second method to confirm abnormal results. A screen result such as “FS” means fetal hemoglobin plus HbS with no HbA, which suggests sickle cell disease. “FAS” is the usual pattern for sickle cell trait.
Diagnostic Tests
Hemoglobin Electrophoresis
Electrophoresis puts hemoglobin in an electric field. Each type moves at its own speed because of its charge. Labs traditionally run it at alkaline pH first, then at acid pH to separate hemoglobins that overlap. For example, HbS and HbD sit at the same spot at alkaline pH but move apart at acid pH. Many labs now use automated capillary electrophoresis in place of the older gel methods.
High-Performance Liquid Chromatography
HPLC passes a blood sample through a column and times how long each hemoglobin takes to come out. It measures HbA, HbS, HbF, HbA2, and HbC, which makes it the workhorse of diagnosis of sickle cell disease in many hospitals. The same measurement, often labeled “HbS percentage” or “HbS quantitation,” is used to check transfusion therapy.
DNA Analysis
Genetic testing of the HBB gene confirms the exact mutation. It’s the test of choice after a recent blood transfusion, when donor cells make protein results hard to read. It’s also used to tell HbSS from HbS/beta-thalassemia and for prenatal diagnosis by chorionic villus sampling or amniocentesis.
Reading a Typical Report
A hemoglobin variant report usually lists each hemoglobin with a percentage. In sickle cell trait, HbA is the larger fraction and HbS the smaller one. In HbSS, HbS dominates, HbF is present in varying amounts, and HbA is absent. In HbSC, HbS and HbC appear in roughly equal amounts. A raised HbA2 alongside HbS, especially with small red cells, points toward sickle beta-thalassemia. Your hematologist reads these figures together with the blood count and family results. They shouldn’t be interpreted one by one in isolation.
Supporting and Monitoring Tests
Once the diagnosis is made, other blood tests track how the disease is behaving:
- Complete blood count (CBC): Measures hemoglobin and red cell indices. Small red cells can point to co-inherited thalassemia.
- Peripheral blood smear: Shows sickled cells, target cells, and signs that the spleen isn’t working.
- Reticulocyte count: Shows how hard the bone marrow is working to replace lost cells. A sudden drop can signal an aplastic crisis.
- Bilirubin and LDH: Markers of red cell breakdown (hemolysis).
- Extended red cell antigen typing: Helps the blood bank match transfusions and lower the risk of antibody formation.
Regular testing is part of lifelong care and relates closely to long-term outlook, which we discuss in our article on the life span of sickle cell patients. For the full picture of the condition, visit our sickle cell guide.
Key Takeaways
- Solubility or “sickle screen” tests only show that HbS is present. They can’t tell trait from disease.
- Hemoglobin electrophoresis, HPLC, and isoelectric focusing identify the exact hemoglobin pattern.
- DNA analysis of the HBB gene settles unclear results and is used for prenatal diagnosis.
- Newborn screening uses HPLC or IEF so that preventive care starts early.
- CBC, reticulocyte count, and HbS percentage are used to monitor the disease once diagnosed.
Frequently Asked Questions
What is the blood test for sickle cell called?
Order forms may list it as “hemoglobinopathy evaluation,” “hemoglobin electrophoresis,” or “HPLC for hemoglobin variants.” A “sickle cell screen” or “Sickledex” is a quicker test that only checks for HbS.
Can a sickle cell test tell if I’m a carrier?
Yes. Electrophoresis or HPLC shows the carrier pattern, where HbA is present alongside a smaller amount of HbS. A solubility test alone can’t make that distinction.
Why was my baby’s sickle test repeated?
Newborn screening results are always confirmed with a second test. That’s because high fetal hemoglobin, prematurity, or a transfusion before the sample was taken can affect the first result. A repeat test doesn’t necessarily mean anything is wrong.
Can a blood transfusion affect sickle cell test results?
Yes. Donor blood adds normal HbA for up to about three months, which can hide the true pattern. In that situation, doctors wait or use DNA testing instead.
