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 hemoglobin variant. Hemoglobin is an iron-containing protein found inside red blood cells (RBCs). It carries oxygen from the lungs to all parts of the body and releases it to the body's cells and tissues. Normally, hemoglobin F (Hb F) is produced by a fetus during gestation. After the baby is born, Hb F is gradually replaced by hemoglobin A (Hb A). Hemoglobin variants – hemoglobin types other than F and A – arise from gene mutations. Many variants have been identified, but only a few are common. They include changes associated with Hb S, Hb C, and beta thalassemia.
A person who has one normal hemoglobin gene copy and one Hb S copy will produce about 20% to 40% hemoglobin S but will produce enough hemoglobin A so that they do not generally experience 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), they produce no normal hemoglobin A but rather 80%–100% hemoglobin S and have 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 altered gene copy of another abnormal hemoglobin variant (doubly heterozygous), such as hemoglobin C or thalassemia. 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 terms "sickle cell disease."
The hemoglobin S mutation results in hemoglobin that is less soluble, or fluid, within the red cell and that may form polymers within the cell during the 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 in and obstruct small blood vessels. When sickled RBCs in circulation are exposed to oxygen in the lungs, they may change back to a disc, but repeated shape changes can damage them and a certain percentage of the cells remain sickled.
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 cells at a much faster rate than normal and release them into the bloodstream as immature red blood cells. They may become increasingly anemic when the body cannot keep up with RBC production.