The test is done as follows: Blood is drawn into a tube that prevents the blood from clotting. Sodium dithionite or a similar chemical is then added to the blood. The sodium dithionite makes the red blood cells “lyse” or break open, releasing the hemoglobin from inside the red blood cells into the blood plasma. Normal hemoglobin, termed “hemoglobin A” dissolves easily in the blood plasma, and the plasma will remain clear, though it will take on a red color. The hemoglobin from a person with sickle cell disease is called “hemoglobin S.” Hemoglobin S does not dissolve easily in blood plasma, and after the sodium dithionite is added the plasma will become cloudy because the hemoglobin S is actually forming small crystals. A person with sickle trait will have both hemoglobin A and hemoglobin S. He or she will have some clouding, but less than with full-blown sickle disease.
If a person has a positive sickle cell solubility, a more sophisticated test called a hemoglobin electrophoresis is usually done to confirm the diagnosis and exclude other conditions that may cause an abnormal sickle cell solubility test.