Sickle cell anemia, also called sickle cell disease, is an inherited disorder that leads to the production of hemoglobin S (HbS or HgbS), 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.

Hemoglobin S production arises from an altered (mutated) gene. A person who has one normal gene copy and one altered copy will produce about 20%-40% hemoglobin S but will produce enough hemoglobin A (the normal hemoglobin) that they do not generally experience any health problems. This single altered copy 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 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 S gene (SS) and those with one copy and a variant (SC, S betathalassemia, SD, SOArab) are all grouped under the terms ‘sickle cell disease’. The hemoglobin 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. Once these polymers are formed, a certain percentage of cells stay in that position and resemble the sickle shape from which the anemia takes its name. [See http://www.ncbi.nlm.nih.gov/disease/sickle.html and http://sickle.bwh.harvard.edu/scd_background.html]

Sickle cell disease is extremely variable. Some patients have very few difficulties, and the disease is discovered accidentally, while other patients have multiple complications. One of the more frequent complications is called “sickle cell painful crisis” and consists of pain in the bones, particularly the long bones, of the body. Although it can arise idiopathically (for an unknown reason), decreased oxygen, infection, dehydration, a change in altitude, and temperature extremes can precipitate a painful episode. It is unclear what actually causes sickle cell crisis, but it appears that some of the less sickled cells stick to the blood vessels and then the abnormally-shaped cells further block (vaso-occlusion) the small veins of the body. This blockage presumably leads to the pain that patients experience during these crises. The symptoms from crises generally resolve in a few days to several weeks. There is little relationship between the number of painful crises and permanent organ damage.

Sickled RBCs are generally short-lived, only lasting about 10-20 days instead of the normal 120 days. To compensate, patients must produce more red cells at a much faster rate than normal and release them into the bloodstream as immature red blood cells. Patients may become increasingly anemic when the body cannot keep up with RBC production. The most common reason for an acute decrease in blood counts is an infection by parvovirus B19, resulting in an “aplastic crisis.”

The three most feared complications of sickle cell anemia are stroke, acute chest syndrome, and infection. Stroke is more common in children than in adults; it occurs in 10% of children with sickle cell anemia. Patients may get lung vaso-occlusion (acute chest syndrome) and, if it occurs repeatedly, lung problems can develop. Patients have an increased incidence of infection, and this is a major cause of mortality in sickle cell disease.

Other complications of sickle cell disease may include gallstones, bone necrosis, kidney disease, increased risk of infection, leg ulcers, retinopathy (disease of the retina in the eye), and priapism (sustained erection). Children are susceptible to inflammation of the fingers (dactylitis) and swollen spleens.

The sickle cell genetic alteration/mutation is found predominantly in people of African ancestry but may also be found in those who can trace their roots to the Mediterranean area, South and Central America, the Middle East, India, and the Caribbean.