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). Hemoglobin is the iron-containing protein found inside red blood cells (RBCs) that carries oxygen from the lungs to all parts of the body and releases it to the body's cells and tissues.
Hemoglobin is made up of heme, which is the iron-containing portion, and globin chains, which are proteins. The globin protein consists of chains of amino acids, the "building blocks" of proteins. There are several different types of globin chains, named alpha, beta, delta, and gamma. Normal hemoglobin types include:
- Hemoglobin A (Hb A): makes up about 95%-98% of hemoglobin found in adults; it contains two alpha (α) chains and two beta (β) protein chains, denoted as α2β2.
- Hemoglobin A2 (Hb A2): makes up about 2%-3% of hemoglobin found in adults; it has two alpha (α) and two delta (δ) protein chains.
- Hemoglobin F (Hb F, fetal hemoglobin): makes up to 1%-2% of hemoglobin found in adults; it has two alpha (α) and two gamma (γ) protein chains. It is the primary hemoglobin produced by the fetus during pregnancy. Shortly after a baby is born, Hb F is replaced by hemoglobin A as the predominant hemoglobin.
Hemoglobin variants – hemoglobin types other than normal hemoglobins F, A, and A2 – arise from either alpha or non-alpha (beta, gamma or delta) globin chains gene mutations. There are currently a few hundred hemoglobin variants identified and described. Hemoglobin Hb S, Hb C, Hb D and Hb E, resulting from mutations of beta-globin chains, are some of the most common hemoglobin variants.
Hemoglobin S results from a mutation affecting the beta-chain of hemoglobin. This mutation can affect either one of the beta chains of Hb A (heterozygote status or HS trait) or both of them (homozygote status or sickle cell disease).
- 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) can be passed on to the 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 or sickle cell disease. 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 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, affected individuals 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, smaller than normal red cells (microcytosis), and an increased number of newly produced red cells called reticulocytes (reticulocytosis).
According to the National Heart, Lung, and Blood Institute, about 100,000 people in the U.S. have sickle cell anemia. It affects about one in 365 African Americans. About one in 13 African Americans are estimated to have sickle cell trait. Other people affected by this disease have Hispanic, southern European, Middle Eastern, and Asian Indian backgrounds.