Starved for Oxygen: The Sickle Cell Crisis

Sickle cell disease is a genetic blood disorder that damages and deforms red blood cells, leading to anemia and episodes of sudden, sometimes severe pain. The disorder affects millions of people throughout the world, and is particularly common among people whose ancestors come from sub-Saharan Africa; Spanish-speaking regions (South America, Cuba, Central America); Saudi Arabia; India and Mediterranean countries such as Turkey, Greece and Italy.

When both parents have the genetic defect that causes sickle cell disease, there's a 25% chance that a child will be born with the disease. Children who inherit the defective gene from only one parent run a 50% chance of carrying the sickle cell trait. People who just carry the sickle cell trait usually don't get the disease, but they can pass the defective gene on to their children.

About 2 million Americans carry the genetic trait for sickle cell anemia and up to 80,000 people, most of whose ancestors came from Africa, actually have the disease.

Starved for Oxygen
The sickle cell problem begins with a protein in the red blood cells called hemoglobin. Hemoglobin contains iron, which binds to oxygen so it can be carried from the lungs to the organs and tissues.

All the organs and tissues of the body need a steady supply of oxygen to stay healthy. Anemia occurs when the amount of red blood cells or hemoglobin becomes too low. People with sickle cell anemia produce abnormal hemoglobin that can clump together and form long, rod-like structures. These structures cause the red blood cells to become stiff and form a half-circle, or "sickle" shape.

Red blood cells with normal hemoglobin are smooth and round and glide through blood vessels. Unlike normal red cells, sickled red cells can't squeeze through small blood vessels. Instead, they stack up and stop the oxygen-carrying blood from reaching the organs and tissues. These episodes, often called crises, are painful and can damage the tissues and vital organs.

Normal red blood cells last about 120 days in the bloodstream, but sickled red cells die after only about 10 to 20 days. Because they can't be replaced fast enough, the blood is chronically short of red blood cells - this is the condition called anemia.

Signs and Symptoms
Some people with sickle cell anemia only have mild symptoms, while others become very ill. However, the basic problem is the same - the sickle-shaped red blood cells can get stuck in narrow blood vessels, blocking the flow of blood. This results in the following conditions:

• Pain. This is the main symptom of sickle cell anemia. It can occur without warning in any organ or joint, wherever the sickled blood cells block oxygen flow. Some patients have a painful crisis less than once a year, and some have as many as 15 or more in a year. Sometimes the pain lasts only a few hours; sometimes it lasts several weeks. For especially severe episodes, the patient might have to be hospitalized for treatment with painkillers and intravenous fluids.
• Fatigue, paleness, and shortness of breath - all symptoms of anemia.
• Hand-foot syndrome. When the small blood vessels in the hands or feet are blocked, pain and swelling can result, along with fever. This may be the first symptom of sickle cell anemia in infants.
• Eye problems. When the retina, the "film" at the back of the eye that receives visual images, does not get enough nourishment from red blood cells, it can deteriorate. Damage to the retina can be serious enough to cause blindness.
• Yellowing of the skin and eyes. These are signs of jaundice, resulting from the rapid breakdown of red blood cells.
• Delayed growth and puberty in children and often a slight build in adults. The slow rate of growth is caused by a shortage of red blood cells.
• Infections. In general, both children and adults with sickle cell anemia are more vulnerable to infections and have a harder time fighting them off once they start. Infants and young children, especially, are susceptible to bacterial infections that can kill in as little as 9 hours. Pneumococcal infections used to be the principal cause of death in young children with sickle cell anemia until physicians began routinely giving penicillin to infants who have sickle cell anemia.
• Acute chest syndrome. This is a life-threatening complication of sickle cell anemia, similar to pneumonia, that is caused by infection or trapped sickled cells in the lung. The symptoms include chest pain, fever, and an abnormal chest x-ray.
• Stroke. The defective hemoglobin damages the walls of the red blood cells, causing them to stick to blood vessel walls. This can result in the development of narrowed, or blocked, small blood vessels in the brain, causing a serious, life-threatening stroke. This type of stroke occurs primarily in children.

Detection
Early diagnosis of sickle cell anemia is critical so that children who have the disease can receive proper treatment. Many states now perform a simple, inexpensive blood test for sickle cell disease on all newborn infants.

As early as the first few months of pregnancy, doctors can do a test to tell whether a fetus has sickle cell anemia or sickle cell trait. Amniocentesis, a procedure in which a needle is used to take fluid from around the baby for testing, can show whether the fetus has sickle cell disease or carries the sickle cell gene.

People who are planning to become parents should know whether they are carriers of the sickle cell gene, and, if they are, they may want to seek genetic counseling. The counselor can tell prospective parents what the chances are that their child will have sickle cell trait or sickle cell anemia. Accurate diagnostic tests and information are available from health departments, neighborhood health centers, medical centers and clinics that care for individuals with sickle cell anemia.

Treatment
Currently the only cure for sickle cell disease is bone marrow transplantation. In this procedure a sick patient receives bone marrow from one of their sisters or brothers. Donors must be healthy, genetically compatible and have the same two parents as the patient. Unfortunately, only about 18% of children with sickle cell disease have a healthy, matched sibling donor. Bone marrow transplantation is a risky procedure with many complications.

Doctors can do a great deal to help sickle cell patients in addition to basic treatment with pain-killing drugs and oral and intravenous fluids.

Blood transfusions, which increase the number of normal red blood cells in circulation, are used to treat and prevent some of the complications of sickle cell anemia.

Giving young children with sickle cell anemia oral penicillin twice a day, beginning when the child is about 2 months old and continuing until the child is at least 5, can prevent pneumococcal infection and early death. Recently, several new strains of pneumonia bacteria that are resistant to penicillin have been reported. Since the vaccines against these bacteria are not effective in young children, studies are being planned to test new vaccines.

The first effective drug treatment for adults with severe sickle cell anemia was reported in 1995, when a study conducted by the National Heart, Lung, and Blood Institute showed that the anti-cancer drug hydroxyurea reduced the frequency of painful crises and acute chest syndrome. Patients taking the drug also needed fewer blood transfusions. The long-term side effects of hydroxyurea and its effects on children with sickle cell anemia are being studied.

Sickle cell anemia patients with severe chest or back pain that prevents them from breathing deeply may be able to avoid lung complications by using an incentive spirometer. This is basically a plastic tube with a ball inside. The patient breathes into it hard enough to force the ball up the tube, so using it helps the patient breathe more deeply.

Leg ulcers are treated with cleansing solutions and zinc oxide, or with skin grafts if the condition persists.

Surgery might be recommended for organ damage, such as to remove gallstones or replace a hip joint. Some types of eye surgery can prevent vision loss.

Maintaining Health
Regular health maintenance is critical for people with sickle cell anemia. Proper nutrition, good hygiene, bed rest, protection against infections, and avoiding stress all are important in maintaining good health and preventing complications. Regular visits to a physician or clinic that provides comprehensive care are necessary to identify early changes in the patient's health and ensure that the person receives immediate treatment.

With good health care, many people with sickle cell anemia are in reasonably good health much of the time and living productive lives. In fact, in the past 30 years, the life expectancy of people with sickle cell anemia has increased. Many patients with sickle cell anemia now live into their mid-40s and beyond.

Scientists have learned a great deal about sickle cell anemia during the past 30 years - what causes it, how it affects the patient, and how to treat some of the complications. They also have begun to have success in developing drugs that will actually prevent the symptoms of sickle cell anemia.

Researchers are experimenting with attempts to cure sickle cell disease by correcting the defective gene and inserting it into the bone marrow of those with sickle cell to stimulate production of normal hemoglobin. Recent experiments show promise and could ultimately provide a cure.

This article includes information from the National Heart, Lung, and Blood Institute and the National Human Genome Research Institute.

Each year, Medical College of Wisconsin physicians care for more than 180,000 patients, representing nearly 500,000 patient visits. Medical College physicians practice at Children's Hospital of Wisconsin, Froedtert Memorial Lutheran Hospital, the Milwaukee VA Medical Center, and many other hospitals and clinics in Milwaukee and southeastern Wisconsin.