The Facts

Sickle cell anemia is an inherited blood disorder that causes chronic anemia, periodic episodes of pain, and other complications. In sickle cell anemia, the red blood cells become rigid and shaped like crescents, or sickles, rather than being flexible and round. This change in shape prevents red blood cells from getting into small blood vessels. As a result, the tissues do not get enough oxygen. Lack of oxygen can cause pain and damage in the arms, legs, and organs (e.g., spleen, kidney, brain).

Sickle cell anemia gets its name from the change of shape (sickling) that happens in the red blood cells. The sickling is caused by an abnormal type of hemoglobin (an iron-protein compound in red blood cells that transports oxygen) known as hemoglobin S.

This disorder is common in the African-descended population of the United States and Canada. It affects millions of people around the world, mainly those whose ancestors come from sub-Saharan Africa, Spanish-speaking regions (South America, Cuba, Central America), Saudi Arabia, India, and Mediterranean countries (Turkey, Greece, and Italy).

Causes

Sickle cell anemia is a genetic disease - those affected have inherited one gene for hemoglobin S from each parent. Those who have only one copy of the gene are carriers of the sickle cell gene and may have deformed red blood cells but don't get sickle cell anemia. This is referred to as sickle cell trait. People with sickle cell trait usually won't have symptoms, except possibly at high altitudes such as during an unpressurized airplane flight. At high altitudes there is less oxygen available, so red blood cells may become more fragile and deformed, increasing their tendency to sickle and break up (hemolysis).

In areas where malaria exists, it was observed that people with the sickle cell trait had a better chance of surviving malaria. People with sickle cell trait are somewhat protected against malaria because the deformed red blood cells prevent malaria from developing.

The basic cause of sickle cell anemia involves hemoglobin, a component of the red cells in the blood. The hemoglobin molecules in each red blood cell carry oxygen from the lungs to organs and tissues and then bring back carbon dioxide for removal by the lungs. In sickle cell anemia, this process is disrupted. After the hemoglobin molecules give up their oxygen, some of them may cluster together and form long, rod-like structures that become stiff and assume a sickle shape. Unlike normal red cells, which are usually smooth and doughnut-shaped, the sickled red cells can't squeeze through small blood vessels. Instead, they stack up and cause blockages that deprive the organs and tissues of oxygen-carrying blood.

Unlike normal red blood cells, which last about 120 days in the bloodstream, sickled red cells die after only about 10 to 20 days. Because they can't be replaced fast enough, the blood may become chronically short of red blood cells, a condition called anemia.

Symptoms and Complications

The symptoms of sickle cell anemia can vary widely in number and severity. However, the most common symptoms are related to anemia and pain. Other symptoms are related to complications. Many people with this condition are in reasonably good health and can live productive lives into their 50s and longer. Some people, however, develop severe symptoms and complications and require frequent hospitalization.

Symptoms of anemia include:

• fatigue
• breathlessness
• rapid heartbeat
• headache
• cold hands and feet
• paleness
• chest pain

Attacks of pain in the abdomen or bones of the arms and legs that lasts from a few hours to several weeks is called sickle cell crisis. Other symptoms include fever and shortness of breath. A crisis can be triggered by infection, too much exercise, sudden changes in temperature, or by no obvious reason.

Complications associated with sickle cell anemia include:

• frequent infections: damage to the spleen from the sickled red cells prevents the spleen from destroying bacteria in the blood (infants and young children are especially at risk for bacterial infections, which can be fatal)
• spleen crisis: the spleen destroys cells, enlarges, and causes anemia that may require blood transfusions
• delayed growth and development: children grow more slowly and reach puberty later than usual because of a lack of red blood cells
• hand-foot syndrome: pain and swelling in the hands and feet due to blockages in the small blood vessels of bones and joints (often the first symptom for infants)
• eye problems: occur when the retina (the "film" at the back of the eye that receives and processes visual images) doesn't get enough nourishment from circulating red blood cells and begins to deteriorate; damage to the retina can be serious enough to cause blindness
• acute chest syndrome: a life-threatening complication of sickle cell anemia that is caused either by infection or by trapped sickled cells in the lungs; symptoms include chest pain, fast breathing, cough, and fever
• pulmonary hypertension: blood pressure in the arteries of the lungs increases due to damaged blood vessels in the lungs
• stroke: narrowed, or blocked small blood vessels in the brain can cause a serious, life-threatening blockage of blood flow to the brain
• priapism: painful erections caused by sickle cells blocking blood flow out of the penis
• gallstones: hemoglobin released from the rapid destruction of red blood cells is broken down into bilirubin - too much bilirubin can cause gallstones to form and may cause yellowing of the skin (jaundice)
• organ failure: lung, liver, or kidney failure can occur
• skin ulcers on the lower legs: some people develop ulcers on the legs

Those who carry the sickle cell trait but don't have the disease usually won't experience any negative effects, except in situations of low oxygen levels or dehydration due to extreme exercise.

Making the Diagnosis

A doctor may suspect sickle cell anemia based on symptoms an on routine blood test results. Early diagnosis of sickle cell anemia in children is extremely important. A simple, inexpensive blood test called hemoglobin electrophoresis is used to confirm the diagnosis, and can be used on newborn infants to screen for the condition.

This test is done at the same time and from the same blood samples as other routine newborn screening tests. It shows if hemoglobin S is present. If the hemoglobin electrophoresis test is positive, the test is repeated to confirm that the child carries the sickle cell trait.

Treatment and Prevention

The only cure for sickle cell anemia at this time is stem cell transplantation. However, this is not available or suitable to all sickle cell anemia sufferers. Despite this, doctors can still do a great deal to help people with sickle cell anemia, and treatment is constantly improving. During painful crises, medications can reduce pain and help avoid complications, and extra fluids can prevent dehydration. Oxygen can be provided if there isn't enough in the bloodstream.

For mild pain, medications such as acetaminophen* and nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen) are tried first. More severe pain may need to be controlled with opioid pain medications (e.g., morphine, oxycodone).

Treatment with hydroxyurea may reduce the frequency of painful crises and of acute chest syndrome for adults and improve growth for children. However, the long-term side effects of hydroxyurea and its effects on complications are still being studied.

When anemia is severe, blood transfusions may be used to treat and prevent complications. Transfusions increase the number of normal red blood cells and fight anemia. Antibiotics may be given to infants and young children to prevent pneumonia, a serious complication of sickle cell anemia. Pneumococcal, H. influenza, and seasonal flu vaccines are recommended to prevent infections, but the vaccines are less effective for people who have had their spleen removed.

Bone marrow transplants have also been used to treat people with sickle cell disease and may cure some people, but the risks and benefits of this procedure must be considered carefully.

Research is ongoing into the possibility of gene therapy (replacing the faulty gene with a normal one). Other studies are focusing on the possibility of turning off the defective gene while at the same time reactivating another gene that turns on production of fetal hemoglobin.

Laser coagulation and other types of eye surgery may be used to prevent further vision loss in those with eye problems. Surgery may be recommended for certain kinds of organ damage, for example, to remove gallstones or replace a hip joint. Leg ulcers may be treated with cleansing solutions and zinc oxide, or with skin grafts if the condition persists.

Regular and preventative health care is critical for people with sickle cell anemia. Proper eating habits, good hygiene, plenty of rest, protection against infections, and avoidance of other stresses are important in maintaining good health and preventing complications. Regular visits to a physician or clinic that provides comprehensive care are necessary so that any problems can be found and treated early and quickly.