What is sickle cell anemia?
Sickle cell anemia, also called sickle cell disease (SCD), is an inherited disorder that leads to the production of hemoglobin S (Hb S or Hgb S), an abnormal form of hemoglobin (hemoglobin variant). An iron-containing protein found inside red blood cells (RBCs), hemoglobin carries oxygen from the lungs to all parts of the body and releases it to the body's cells and tissues. Hemoglobin F (Hb F, baby or fetal hemoglobin), a normal type of hemoglobin, is the predominant hemoglobin produced by a fetus during gestation. Shortly after a baby is born, Hb F is replaced by hemoglobin A (Hb A, adult hemoglobin) as the predominant hemoglobin. Hemoglobin variants – hemoglobin types other than F, A, and A2 (a minor type of normal hemoglobin) – arise from gene mutations. Many variants have been identified, but only a few are common, including Hb S, Hb C, and Hb E.
A person who has one normal hemoglobin gene copy and one Hb S copy will produce about 40% hemoglobin S but will produce enough hemoglobin A (about 60%) so that he or she does not generally experience significant health problems. This single altered copy (heterozygous) is called sickle cell trait and it can be passed on to a person's children. When a person has two copies of the altered gene (homozygous), the person produces 80-90% hemoglobin S, no normal hemoglobin A, and has sickle cell anemia. Symptoms and complications of sickle cell disease may also be experienced by people who have one sickle cell gene copy and one gene copy for another hemoglobin variant (doubly heterozygous), such as hemoglobin C or the variants seen with beta thalassemia, a group of blood disorders resulting from gene mutations that decrease normal hemoglobin production. People with two copies of the Hb S gene (SS), and those with one copy and a variant (SC, S beta thalassemia, SD, SOArab), are all grouped under the term "sickle cell disease."
The hemoglobin S mutation results in hemoglobin that is less soluble, or fluid, within a red blood cell, which reduces the efficiency of oxygen exchange and can cause the formation of polymers in the cell during normal stages of oxygen transport. These polymers can change the shape of the RBC from a round disc to a characteristic sickle shape, especially in reduced oxygen environments. The altered shape limits the RBC's ability to flow smoothly throughout the body. The sickled cells can become stuck and obstruct small blood vessels, causing tissue damage.
Sickled RBCs are generally short-lived, only lasting about 10-20 days instead of the normal 120 days. To compensate, those who are affected must produce more red blood cells at a much faster rate and release them into the bloodstream earlier. They may become increasingly anemic when the body cannot keep up with the rapid RBC destruction, resulting in a condition known as hemolytic anemia.