Sickle Cell Anemia

by Food and Drug Administration (FDA)

In tropical regions of the world where the parasite-borne disease malaria is prevalent, people with a single copy of a particular genetic mutation have a survival advantage. Over time, people from these regions have migrated, had children, and in some cases married each other. Some of their children inherit two copies of the mutation.

While inheriting one copy of the mutation confers a benefit, inheriting two copies is a tragedy. Children born with two copies of the genetic mutation have sickle cell anemia, a painful disease that affects the red blood cells and is curable only in rare instances.

In February 1998, the Food and Drug Administration approved the drug Droxia (hydroxyurea) for reducing painful episodes in adults with a severe form of sickle cell anemia. The drug doesn't cure the disease. Hydroxyurea also is approved under the name Hydrea for treating certain cancers.

Genetic Defect Changes Cell Shape

The genetic defect that causes sickle cell anemia affects hemoglobin, a component of red blood cells. Hemoglobin's job is to carry oxygen to all the cells and tissues of the body. Red blood cells that contain normal hemoglobin (such as the one pictured top right) are soft and round. Their soft texture enables them to squeeze through the body's small blood vessels.

People with sickle cell anemia, however, have a type of abnormal hemoglobin called hemoglobin S. (Normal hemoglobin is called hemoglobin A.) A genetic error makes the hemoglobin molecules stick together in long, rigid rods after they release oxygen. These rods cause the red blood cells to become hard and sickle-shaped, unable to squeeze through tiny blood vessels. The misshapen cells (like the one pictured bottom right) can get stuck in the small blood vessels, causing a blockage that deprives the body's cells and tissues of blood and oxygen.

When this happens "it's like having mini heart attacks throughout the entire body," said Duane R. Bonds, M.D., leader of the sickle cell disease scientific research group at the National Heart, Lung, and Blood Institute (NHLBI), which is a component of the National Institutes of Health, in Bethesda, Md.

"A heart attack is painful because the blood flow to the heart is interrupted. In sickle cell anemia, the blood flow can be interrupted to any of the major organs, causing severe pain and organ damage at the site of the blood flow blockage."

These painful "crises," as they are called, damage the lungs, kidneys, liver, bones, and other organs and tissues. Recurrence of these episodes is the most disabling feature of sickle cell anemia. They can cause leg ulcers, blindness, and many other health problems, depending upon where in the body the blood flow blockage occurs. A blockage in the brain can cause a stroke, which may result in paralysis or death.

The body, recognizing that the sickled cells are abnormal, destroys them at a faster rate than it can replace them. This causes a type of anemia, a shortage of red blood cells. Symptoms of anemia include extreme fatigue and susceptibility to infection.

Penicillin Treatment

An important breakthrough occurred in 1986 when an NHLBI-sponsored study found that young children with sickle cell anemia who took penicillin twice a day by mouth had much lower rates of S. pneumoniae infection than a similar group of children who received a placebo.

In 1987, an expert panel convened by NHLBI recommended that all infants born in the United States be screened for sickle cell anemia so that children with the disease could be identified early and offered treatment with penicillin. Forty-two states now have newborn screening programs, according to Bonds. NHLBI also recommends that affected infants get daily penicillin therapy beginning by the age of 3 months.

In the first year of life, children with sickle cell anemia are protected from blood flow blockages by the presence of fetal hemoglobin.

"Fetal hemoglobin is the hemoglobin that all of us produce before we're born," explained Bonds. Fetal hemoglobin physically blocks hemoglobin S, preventing it from forming the long, rigid rods that lead to sickling of the red blood cells. Several weeks before birth, however, the fetus' bone marrow usually begins to shut down the production of fetal hemoglobin and starts making adult hemoglobin instead. At birth, an infant's red blood cells contain roughly equal amounts of fetal and adult hemoglobin.

By the time the child is 6 months old, it has usually stopped making any fetal hemoglobin. As the level of fetal hemoglobin in the child's blood falls, explained Bonds, there is no longer anything to prevent the red blood cells from becoming sickle-shaped and getting stuck in the blood vessels, causing a painful crisis.

The symptoms of a painful crisis may be relieved by giving patients fluids and painkillers, said Lilia Talarico, M.D., director of the division of gastrointestinal and hematologic drug products in FDA's Center for Drug Evaluation and Research. Hydroxyurea is the only FDA-approved treatment currently available to prevent painful crises from occurring. Transfusions and blood exchange transfers may be necessary to manage infections and other seriou complications of sickle cell disease such as stroke and acute chest syndrome, as well as for surgical procedures.

About the Author

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