Sickle Cell Disease

• What is sickle cell disease?
• What medical problems occur with sickle cell disease?
• Can a person catch sickle cell disease from someone who has it?
• Do we all have the same chance of inheriting sickle cell disease?
• Is sickle cell trait the same thing as sickle cell disease?
• What are the chances that parents with sickle cell trait will pass it on to their children?
• Can a woman with sickle cell disease have a safe pregnancy?
• Is there a test for sickle cell disease or trait?
• Where is sickle cell testing and treatment available?
• Is there a cure for sickle cell disease?
• What other new treatments are being developed?
• Is the March of Dimes supporting research on sickle cell disease?
• For more information
• References

What is sickle cell disease?
Sickle cell disease is an inherited disease of red blood cells. Individuals with sickle cell disease have abnormal hemoglobin, the protein inside red blood cells that carries oxygen to every part of the body. The abnormal hemoglobin causes the red blood cells to become C-shaped (like a farm tool called a sickle) and stiff.

Normally, red blood cells are round and flexible and flow easily through blood vessels. Stiff red blood cells get stuck in tiny blood vessels, cutting off the blood supply and causing pain and, sometimes, organ damage. Sickle-shaped red blood cells die and break down more quickly than normal red blood cells, resulting in anemia.

There are several common forms of sickle cell disease:

• Hemoglobin SS: The individual inherits one sickle cell gene from each parent. This is the most common form.
• Hemoglobin SC: The individual inherits one sickle cell gene and one gene for another abnormal type of hemoglobin called “C.”
• Hemoglobin S-beta thalassemia: The individual inherits one sickle cell gene and one gene for beta thalassemia, another inherited anemia.

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What medical problems occur with sickle cell disease?
The effects of sickle cell disease vary greatly from one person to the next. Some affected individuals are generally healthy, while others are frequently hospitalized. Common problems seen in sickle cell disease include the following:

Anemia: Individuals with sickle cell disease have a decreased number of red blood cells. As a result, they may be pale, tire easily and have shortness of breath.

Infections: Infants and young children with sickle cell disease have an increased risk of contracting serious bacterial infections, such as pneumonia and meningitis (infection of the lining of the brain). Infections are a major cause of death in children with sickle cell disease.

But deaths have declined dramatically since providers began routinely treating children with sickle cell disease with the antibiotic penicillin to help prevent infections. Affected children should receive penicillin twice daily between the ages of 2 months and 5 years of age (1, 2).

All states now screen newborns for sickle cell disease as part of a panel of newborn screening tests (2). Early identification of affected babies alerts health care providers to begin treatment before dangerous infections occur.

It is important for babies and children with sickle cell disease to be given regular childhood vaccinations. The Hib (Hemophilus influenzae b) vaccine and the pneumococcal vaccine (Prevnar) help protect against potentially life-threatening bacterial infections. These vaccines are recommended for all babies starting at 2 months of age. Children with sickle cell disease should be given additional vaccinations, including (2, 3):

• Flu (influenza) shot: This should be given every year, beginning at 6 months of age.
• Pneumococcal vaccine (23-valent pneumococcal vaccine): This protects against additional types of bacteria. It is given at 2 and 5 years of age.
• Meningococcal vaccine: This vaccine, which protects against meningitis, is given after age 2.

Pain episodes: These are the most common symptom of sickle cell disease. Some affected individuals have one or fewer pain episodes a year, while others may have 15 or more (3). Pain episodes usually last a few hours to a few days, but they may sometimes last for weeks. Pain can occur in any organ or joint in the body, wherever sickle-shaped cells pile up and block blood vessels.

Mild pain episodes can be treated at home with over-the-counter pain medications (such as acetaminophen and ibuprofen) and heating pads. But some pain episodes may be severe and need to be treated in the hospital with strong pain-killing drugs.

The following steps may help prevent pain episodes in some affected individuals (2, 4):

• Drink plenty of fluids.
• Avoid getting too hot or too cold.
• Avoid places with high altitudes where oxygen levels are low.
• Avoid extreme exercise.
• Limit emotional stress.

Severely affected adults can take a drug called hydroxyurea. A 1995 study reported that treatment with hydroxyurea reduces the number of pain episodes in severely affected adults by about 50 percent (5). A 2003 study that followed the same patients for nine years found that treatment with hydroxyurea reduced deaths by 40 percent (6).

Some studies have found that hydroxyurea is effective and well tolerated in children in the short term (4). However, the drug is not yet routinely recommended in children because it is not known whether it has any adverse effects on growth and development. Researchers continue to study the long-term safety of the drug in children.

Hand-foot syndrome: Hands and feet may swell when small blood vessels become blocked. This may be the first symptom of sickle cell disease in babies, who also may develop a fever. It usually is treated with pain medication and fluids.

Stroke: A stroke can occur when sickle-shaped cells block a blood vessel in the brain. About 10 percent of children with sickle cell disease have a stroke (2, 4). Stroke can lead to lasting disabilities, including learning problems.

Providers can sometimes identify children who are at increased risk for stroke using a special type of ultrasound examination. In some cases, a provider may recommend regular blood transfusions to help prevent a stroke.

A 1998 study found that regular transfusions greatly reduce the risk of a first stroke in high-risk children with sickle cell disease (7). Regular transfusions also reduce the risk of another stroke in children who already have had a stroke. A recent study showed that this treatment must be continued indefinitely because when treatment is stopped, a high risk of stroke returns (8). Unfortunately, regular transfusions pose some major risks, including a potentially fatal buildup of iron in the body. Children who receive regular transfusions must undergo treatment aimed at reducing iron levels.

Splenic crisis: The spleen is an organ that removes worn- out red blood cells and helps fight infection. In sickle cell disease, the spleen may become dangerously enlarged because it is clogged up with abnormal red blood cells. Symptoms include pain on the left side of the abdomen, weakness and rapid heart rate. This condition is treated in the hospital with blood transfusions. If the condition recurs frequently, the provider may recommend regular blood transfusions or removal of the spleen.

Acute chest syndrome: This is similar to pneumonia, with symptoms such as difficulty breathing, chest pain and fever. It can be caused by an infection or by blocked blood vessels in the lung. This potentially life-threatening disorder should be treated in the hospital. Treatments may include antibiotics, blood transfusions, pain medications, oxygen and medicines that help open up blood vessels and improve breathing.

Vision problems: When tiny blood vessels in the eye become blocked with sickle-shaped cells, vision problems and even blindness can result. Some individuals with sickle cell disease may need regular eye exams. When eye problems occur, laser treatment often prevents further vision loss.

Slow growth: Children with sickle cell disease tend to grow slower than normal and enter puberty later than other children due to anemia.

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Can a person catch sickle cell disease from someone who has it?
No. The disease is not contagious. It is inherited. To inherit the disease, a child must receive two sickle cell genes, one from each parent.

Do we all have the same chance of inheriting sickle cell disease?
No. In the United States, most cases occur among African-Americans and Hispanic-Americans. About 1 in every 500 African-Americans and about 1 in every 1,000 to 1,400 Hispanic-Americans has sickle cell disease (2). It also affects people of Arabian, Greek, Maltese, Italian, Sardinian, Turkish and Indian ancestry.

Is sickle cell trait the same thing as sickle cell disease?
No. A person who inherits the sickle cell gene from one parent and the normal type of that gene from the other parent is said to have sickle cell trait. One in 12 African-Americans and 1 in 100 Hispanic-Americans has sickle cell trait (2, 9). They generally are as healthy as individuals who do not have the trait. Sickle cell trait cannot become sickle cell disease. However, when two people with sickle cell trait have a child, their child may inherit two sickle cell genes and have the disorder.

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What are the chances that parents with sickle cell trait will pass it on to their children?
In each pregnancy of two parents who both have sickle cell trait, there is a:

• Fifty percent chance that the child will have the trait
• Twenty-five percent chance that the child will have sickle cell disease
• Twenty-five percent chance that the child will have neither the trait nor the disease

If only one parent has the trait and the other has no abnormal hemoglobin gene, there is no chance that their children will have sickle cell disease. However, there is a 50-50 chance of each child having the trait.

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Can a woman with sickle cell disease have a safe pregnancy?
Yes. However, women with sickle cell disease are at increased risk for complications that can affect their health and that of their babies. During pregnancy, sickle cell disease may become more severe, and pain episodes may occur more frequently. A pregnant woman with sickle cell disease is at increased risk for miscarriage, for preterm labor, and for having a low-birthweight baby (10). However, with early prenatal care and careful monitoring throughout pregnancy, women with sickle cell disease can have a healthy pregnancy. Treatment with hydroxyurea is not recommended during pregnancy because it can increase the risk of birth defects (10).

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Is there a test for sickle cell disease or trait?
Yes. A blood test can determine if a person has either sickle cell trait or a form of the disease. There also are prenatal tests (amniocentesis and chorionic villus sampling) to find out if a baby will have the disease or carry the trait.

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Where is sickle cell testing and treatment available?
Couples who are planning to have a baby can get testing for sickle cell trait at medical centers and sickle cell treatment facilities. A genetic counselor can refer a couple for testing and discuss the risks to their offspring. Their health care provider also should be able to refer them to local sickle cell resources.

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Is there a cure for sickle cell disease?
A small number of children with severe sickle cell disease have been cured through a blood stem cell transplant. The stem cells (immature cells that develop into blood cells) come from bone marrow, or less frequently from umbilical cord blood, usually donated by siblings who are a good genetic match. Most children with sickle cell disease, however, do not have siblings who are good genetic matches.

More than 200 children worldwide with sickle cell disease have had blood stem cell transplants, and about 85 percent of them appear to be cured of the disease (11). However, this approach carries a high risk: About 5 percent of children who underwent bone marrow transplants died. The transplant did not cure the disease in another 10 percent (11). Gene therapy may someday offer a cure with less risk.

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What other new treatments are being developed?
Currently, researchers are studying a number of new drug treatments that may reduce complications of the disease. Like hydroxyurea, decitabine and butyrate (a food additive) appear to cause the body to make a form of hemoglobin (fetal hemoglobin) that a baby makes before birth. Increased levels of fetal hemoglobin appear to help prevent red blood cells from sickling. Other treatments that may help prevent sickling include:

• Nitric oxide (a gas that can be inhaled)
• L-arginine (an oral dietary supplement that appears to boost the body's production of nitric oxide)
• Clotrimazole (an oral anti-fungal drug)
• Certain blood-thinning drugs

Researchers also are comparing the effectiveness of hydroxyurea to regular transfusions in preventing stroke in high-risk children (4). In the future, this drug may make treatment simpler and safer for these children.

There already has been a great deal of progress in medical care that reduces serious complications and improves survival in individuals with sickle cell disease. New treatments may further improve the quality of life in affected individuals.

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Is the March of Dimes supporting research on sickle cell disease?
The March of Dimes has been a major supporter of sickle cell disease research. Recent grantees have been seeking to develop new treatments to prevent pain episodes and organ damage, including new approaches to gene therapy.

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For more information

Sickle Cell Disease
Centers for Disease Control and Prevention (CDC)

Sickle Cell Disease
National Heart, Lung and Blood Institute

Sickle Cell Disease Association of America
231 East Baltimore Street, Suite 800
Baltimore MD 21202
(800) 421-8453

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References

1. American Academy of Pediatrics, Section on Hematology/Oncology. Health Supervision for Children with Sickle Cell Disease. Pediatrics, volume 109, number 3, March 2002.
2. Centers for Disease Control and Prevention (CDC). Sickle Cell Disease. Accessed 12/14/07.
3. National Heart, Lung, and Blood Institute. Sickle Cell Anemia. Accessed 12/14/07
4. Driscoll, M.C. Sickle Cell Disease. Pediatrics in Review, volume 28, number 71, July 2007, pages 259-268.
5. Charache, S., et al. Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia. New England Journal of Medicine, 1995, volume 332, pages 1317-1322.
6. Steinberg, M.H., et al. Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia. Journal of the American Medical Association, volume 289, number 3, April 2, 2003, pages 1645-1651.
7. Adams, R.J., et al. Prevention of a First Stroke by Transfusions in Children with Sickle Cell Anemia and Abnormal Results on Transcranial Doppler Ultrasonography. New England Journal of Medicine, volume 339, number 1, July 2, 1998, pages 5-11.
8. Optimizing Primary Stroke Prevention in Sickle Cell Anemia (Stop 2) Trial Investigators. Discontinuing Prophylactic Transfusions Used to Prevent Stroke in Sickle Cell Disease. New England Journal of Medicine, volume 353, number 26, December 29, 2005, pages 2769-2778.
9. National Human Genome Research Institute. Learning About Sickle Cell Disease. Updated 11/27/07.
10. American College of Obstetricians and Gynecologists (ACOG). Hemoglobinopathies in Pregnancy. ACOG Practice Bulletin, number 78, January 2007.
11. Krishnamurti, L. Hematopoietic Cell Transplantation for Sickle Cell Disease: State of the Art. Expert Opin. Biol. Ther., volume 7, number 2, 2007, pages 161-172.

February 2008

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