Sickle Cell Disease

Topic Overview

What is sickle cell disease?

Sickle cell disease changes normal, round red blood cells into cells that can be shaped like crescent moons. The name “sickle cell” comes from the crescent shape of the cells. A sickle is a farm tool with a curved blade that can cut crops like wheat.

Normal red blood cells move easily through your blood vessels, taking oxygen to every part of your body. But sickled cells can get stuck and block blood vessels, which stops the oxygen from getting through. That can cause a lot of pain. It can also harm organs, muscles, and bones.

See a picture of sickle cells blocking a blood vessel.

Having sickle cell disease means a lifelong battle against the health problems it can cause, such as pain, infections, anemia, and stroke. But many people are able to have a very good quality of life by learning to manage the disease.

What causes sickle cell disease?

Sickle cell disease is inherited, which means it is passed from parent to child. To get sickle cell disease, a child has to inherit two sickle cell genes—one from each parent.

When a child inherits the gene from just one parent, that child has sickle cell trait. Having this trait means that you do not have the disease but you are a carrier and could pass the gene on to your children.

What are the symptoms?

Painful events are the most common symptom of sickle cell disease. They are periods of pain that happen when sickled cells get stuck in blood vessels and block the blood flow. These events usually cause pain in the hands, feet, belly, back, or chest. The pain may last for hours or for days.

People with sickle cell disease often have anemia, caused by a shortage of red blood cells. Anemia makes you feel weak and tired. People with sickle cell anemia may look pale or washed out. Their skin and the whites of their eyes may have a yellowish look (jaundice).

Doctors cannot yet tell which symptoms a child born with sickle cell disease will have, when they will start, or how serious they will be.

How is sickle cell disease diagnosed?

A simple blood test can show whether a person has sickle cell disease. Most states test for sickle cell disease before infants go home from the hospital.

How is it treated?

Early treatment includes daily antibiotics from 2 months to 5 years of age to help prevent infections. Routine childhood immunizations are also important.

Managing pain is often a big part of having sickle cell disease. You can prepare for a painful event ahead of time by creating a pain management plan with your doctor. The plan should include what you can do at home to relieve pain for yourself or your child. The plan should also tell you when it is best to call a doctor or go to a hospital.

Some people need regular blood transfusions to lower the risk of stroke and treat anemia and other problems.

Regular checkups are an important part of life with this disease. People with sickle cell disease need a good working relationship with a doctor who is an expert in treating it.

How do you manage life with sickle cell disease?

• Learn what triggers, or sets off, painful events. Triggers often include cold temperatures, wind, dehydration, and too much exercise. Low oxygen caused by cigarette smoke, high altitude, and plane flights is another common trigger.
• Make sure that your child takes antibiotics regularly until age 5 to prevent infections. And make sure he or she receives all the usual immunizations on schedule.
• Your child can take part in normal school activities. Make sure that teachers understand your child’s special needs, like needing frequent drinks and bathroom trips and avoiding overexertion and cold temperatures.
• People with sickle cell disease and their families face ongoing stress. A support network can help ease stress and worry. Ask your doctor if there is a support group in your area. You can also find Web sites on the Internet where you can ask questions, share your feelings, and get advice.

Frequently Asked Questions

Cause

Sickle cell disease is an inherited disorder. More specifically, sickle cell disease is an autosomal recessive disease. This means that to have the disease, you must inherit a gene for the disease from both parents.

• Normally, a person inherits two genes that tell the body to produce normal hemoglobin A. One gene comes from each parent.
• People who inherit one defective hemoglobin S gene and one normal hemoglobin A gene have sickle cell trait. These people don't have symptoms of sickle cell disease nor do their bodies make sickled blood cells. But they can pass the defective hemoglobin S gene to their children.
• Sickle cell disease occurs when a person inherits one defective hemoglobin S gene from each parent.
• Similar sickle cell disorders occur when a person inherits a hemoglobin S gene from one parent and another type of defective hemoglobin gene from the other parent. Sickle cell disease is a sickle cell disorder.

Symptoms

Painful events (crises) in the hands or feet, abdomen, back, or chest are the most common symptom of sickle cell disease. This pain may last from hours to days. Most people with sickle cell disease experience anemia. Symptoms of anemia include feeling weak and tired. People with sickle cell disease can appear pale or washed out. Or they have a yellowish look to their skin and the whites of their eyes (jaundice).

When a child is born with sickle cell disease, it isn't possible to predict which symptoms will appear, when they will start, or how bad they will be. Most symptoms of sickle cell disease are related to either long-term (chronic) anemia or blood vessels blocked by sickled cells.

Symptoms related to chronic anemia

Most people who have sickle cell disease have at least mild symptoms of chronic anemia, which may include:

• Weakness.
• Tiredness (fatigue).
• Pale appearance.
• Yellowing of the skin and the whites of the eyes (jaundice).
• Shortness of breath, especially when they are active.

Severe anemia may raise the chance of a person with sickle cell disease getting high blood pressure in the lungs (pulmonary hypertension), and this can be deadly.¹

Symptoms caused by blocked blood vessels

Pain symptoms caused by blocked blood vessels in bones, organs, and other tissues include hours to days of extreme pain. These painful events can occur rarely to often. Sometimes home treatment can help the pain. And sometimes a hospital stay is needed.

Children ages 6 months to 4 years may have episodes of extreme pain in the hands, the feet, or both (hand-foot syndrome).

What Happens

Normal red blood cells have a 120-day life span. But people born with sickle cell disease have sickle-shaped blood cells that usually live no more than 20 days. These sickled cells can get stuck in blood vessels, blocking blood flow. See a picture of sickle cells blocking a blood vessel.

Lesser blood flow can damage the body's organs, muscles, and bones, sometimes leading to life-threatening conditions. Sickle cell disease may cause problems such as:

• Painful events (vaso-occlusive complication), which result when blood vessels are blocked. This is a common condition of sickle cell disease.
• Splenic sequestration, usually seen in children age 6 months to 2 years during or after a simple respiratory infection. Large numbers of sickled red blood cells become trapped in the spleen. It can cause sudden and life-threatening anemia.
• Acute chest syndrome, most common in children but more severe in adults. Coughing and chest pain are symptoms of acute chest syndrome, which may occur after an infection or painful event.
• Severe infections, especially in children younger than 3.
• Aplastic crisis, which may occur after infection with some viruses. During an aplastic crisis, bone marrow stops producing red blood cells, which results in sudden and severe anemia.

When a child is born with sickle cell disease, it's impossible to predict which problems will develop, when they will start, or how bad they will be. During the first 6 months of life, infants have a high level of fetal hemoglobin (HbF) in their blood, which protects them from red blood cell sickling. But dangerous complications of sickle cell disease may quickly develop between ages 6 months and 5 years, after levels of fetal hemoglobin decrease. Normal red blood cells have a 120-day life span, but sickled blood cells usually live no more than 20 days. When bone marrow can't produce enough red blood cells to keep up with sickled blood cell loss, severe anemia may develop.

Older children and adults with sickle cell disease may have few problems or have a pattern of ongoing complications that shortens their lives. The most common and serious problems caused by sickle cell disease are anemia, pain, and organ failure. Stroke affects around 10% of children with sickle cell disease.²

Other complications of sickle cell disease include:

• Growth slowdown. Children with sickle cell disease often grow more slowly than normal and go through puberty later than children who don't have sickle cell disease.
• Open sores (ulcers) on the legs and feet, commonly during adulthood. These ulcers can be very painful and heal slowly. Some may last for years.
• Eye damage. Long-term vision problems may result from blocked blood flow in the inner lining of the eye (retina).

People who have sickle cell disease live to age 50 to 60, on average.³ A lot depends on the type of sickle cell disorder and how it affects a person's health.

What Increases Your Risk

Risk of inheriting sickle cell diseaseSickle cell disease is an inherited blood disorder, passed from parent to child. Children with sickle cell disease have two defective genes, one from each parent. Various forms of sickle cell disorder occur when a person inherits one sickle cell gene and one other type of defective hemoglobin gene.

People who inherit one defective hemoglobin S gene and one normal hemoglobin A gene have sickle cell trait. They don't have symptoms of sickle cell disease nor do their bodies make sickled blood cells. But they have a 50% chance of passing the defective hemoglobin S gene to each of their children.

• If both parents have sickle cell trait, each of their children will have a 1-out-of-4 (25%) chance of having sickle cell disease.
• If one parent has sickle cell disease (has two genes for making hemoglobin S) and the other has sickle cell trait (has one hemoglobin S gene and one normal hemoglobin A gene), each of their children will have a 1-out-of-2 (50%) chance of having sickle cell disease and a 1-out-of-2 (50%) chance of having sickle cell trait.
• If one parent has sickle cell disease (two hemoglobin S genes) and the other has two normal hemoglobin A genes, each of their children will have sickle cell trait. None of the children will have sickle cell disease.

People whose ancestors were from Africa, India, the Middle East, the Mediterranean (Turkey, Italy, Greece), and some Latin American countries are more likely to inherit the gene that can cause sickle cell disease. In the United States, the disease mainly affects African Americans (1 out of 650) and Latin Americans (1 out of 1,000 to 1,400).⁴

For more information, see a picture of the risk of passing on an autosomal recessive disease such as sickle cell disease.

Risk of painful events and complications caused by sickling Triggers that can cause red blood cells to sickle include:

• Lack of oxygen because of:
  • Cigarette smoke. Both smoking and inhaling smoke from other people's cigarettes (secondhand smoke) can damage the lungs and lower oxygen levels in the blood. Children and adults who have sickle cell disease should avoid cigarette smoke.
  • High altitude [locations higher than 5000 ft (1524 m)]. There is less oxygen in the air at high altitudes.
  • Air travel. Because there is less oxygen at high altitudes, flying in an unpressurized airplane can cause cells to sickle. Large passenger airplanes are pressurized. But a person with sickle cell disease may have a sickling problem even when flying in a pressurized airplane. Most people won't have problems if they are flying only for a short time (less than 4 to 6 hours) and drink plenty of fluids during the flight.
• Cold temperatures and wind. Exposure to cold air, wind, and water may cause a painful event by triggering red blood cell sickling in exposed areas of the body.
• Loss of fluid (dehydration). Dehydration may slow blood flow in the body, which increases the chance of having a painful event.
• Infection. Painful events are commonly triggered by infection.
• Stress. Increased stress may bring on painful events.
• Strenuous exercise. Dehydration and reduced oxygen levels in a person's blood resulting from strenuous exercise may cause red blood cells to sickle. Many people with sickle cell disease can tolerate moderate exercise if they rest when they feel tired and drink plenty of fluids.

When To Call a Doctor

Call 911 or other emergency services immediately if you have sickle cell disease and one or more of the following symptoms are present:

• Difficulty breathing or shortness of breath
• Chest pain
• Severe abdominal pain
• Sudden weakness
• Sudden numbness or tingling in the hands, feet, fingers, or toes (even if it goes away on its own)
• Sudden poor balance and poor coordination when walking (even if it goes away on its own)
• Confusion (even if it goes away on its own)
• Garbled speech or an inability to speak (even if it goes away on its own)
• Sudden change in vision
• Severe headache
• Loss of consciousness
• Fever higher than 101°F (38.33°C)
• Severe cough
• Repeated vomiting or persistent diarrhea
• A sudden increase in the size of your or your child's spleen (Learn from your doctor how to feel your child's spleen to check its size.)
• Increased paleness
• Lightheadedness
• Persistent erection of the penis (priapism) that lasts more than 3 hours or is extremely painful
• Severe pain that can't be relieved with your usual prescription painkilling drugs or other pain-relief methods

Call your doctor if you or your child has any of the following symptoms:

• A painful event
• An open sore (ulcer) on the leg
• More frequent urination than usual

Make a plan with your doctor that includes where and when to get treatment in case of a sickle cell emergency.

Watchful Waiting

Watchful waiting is when you and your doctor watch your symptoms to see if your health improves on its own. If it does, no treatment is necessary. If your symptoms don't get better or get worse, then it’s time to take the next treatment step. Some complications of sickle cell disease may not need immediate medical attention from a doctor. In these cases, you can try home treatment.

Painful events can be treated at home depending on how severe the pain is and how long you've had it. Try over-the-counter pain medicine for mild pain. Or take a stronger medicine, if prescribed by your doctor. If this doesn't work, contact your doctor or seek emergency medical treatment.

You may treat persistent, painful erection of the penis (priapism) at home by drinking fluids, taking over-the-counter pain medicine, and urinating as much as possible. If this doesn't solve the problem within 2 to 3 hours, seek emergency medical treatment.⁵

Who To See

If you or your child has sickle cell disease, try to find a doctor who has special training for this disease. Some medical centers and hospitals specialize in sickle cell disease treatment and support. If your local community doesn't offer this option, look for a doctor and a pain treatment specialist who have experience in treating sickle cell disorders. Choose a doctor you are comfortable with and can partner with over the long term.

The following types of health professionals can diagnose and help treat symptoms of sickle cell disease. Some of these health professionals may provide specialized treatment or counseling.

• Hematologist
• Family medicine physician
• General practitioner
• Pediatrician
• Pain management specialist
• Pediatric hematologist-oncologist
• Pulmonologist
• Neurologist
• Ophthalmologist
• General surgeon
• Medical geneticist

To prepare for your appointment, see the topic Making the Most of Your Appointment.

Exams and Tests

Sickle cell disease is diagnosed when initial tests show abnormal hemoglobin, with more testing if needed. A sickle cell test looks for sickle cell trait and sickle cell disease.

Prenatal testing

Doctors can diagnose sickle cell disease before a child is born (prenatally). Couples who are at risk for passing on this disease to their offspring may want to talk with a genetic counselor about prenatal testing.

• During pregnancy, doctors use amniocentesis or chorionic villus sampling (CVS) to see whether the fetus has sickle cell disease.
• Some couples choose to end a pregnancy if the fetus is found to have sickle cell disease.

Infant screening

Sickle cell disease can be diagnosed at birth. Most states in the United States screen all newborns for sickle cell disease along with other common disorders. You can also request screening.

Soon after birth, a sample of blood is taken from the infant's heel and sent to a lab, where it is screened for the presence of sickle cell hemoglobin (hemoglobin S).

Adult screening

If one member of a couple has sickle cell disease or sickle cell trait, the other member should be tested before becoming pregnant. This test requires a blood sample, which is screened for the presence of hemoglobin S, hemoglobin C, or beta-thalassemia.

If one or both members of a couple carry a hemoglobin S gene or another abnormal hemoglobin gene, the couple may want to meet with a genetic counselor before becoming pregnant to learn more about their chances of having a child with sickle cell disease. Your doctor can help you find a genetic counselor to discuss a genetic test.

Pulmonary hypertension is a severe, common problem for people with sickle cell disease. It can be detected early with an echocardiogram, a painless method of measuring blood flow. Some experts suggest all adults with sickle cell disease get screened.^{1, 3}

Treatment Overview

Successful treatment of sickle cell disease requires:

• The latest treatment and home care information for families affected by sickle cell disease.
• A partnership between the family, a doctor experienced in sickle cell disease treatment, and other health professionals, as needed, to provide full care for symptoms that involve different body systems.
• Immediate treatment for sudden, serious problems and complications.

Initial treatment

When parents learn that their baby has sickle cell disease, it's the beginning of a lifelong education process. Knowing as much as possible about the disease can help you control symptoms as they arise and know what to do in emergency situations. Initial treatment includes:

• Routine childhood immunizations and other vaccines.
• Daily antibiotics from 2 months to 5 years of age.
• Multivitamin supplements with iron during infancy.
• Folic acid supplements daily.
• Protein supplements if there is a lag in weight gain.

Starting at age 2 years, your child should get screened every now and then with a transcranial ultrasound.⁶ This test measures blood flow in the arteries of the head and neck. If test results show a high chance for stroke, your child may get blood transfusions to lower the risk.²

Ongoing treatment

Children age 1 to 5 with sickle cell disease often receive daily antibiotics, such as penicillin, to prevent life-threatening infections. This practice stops at age 5 because older children don't have as many severe infections.

Routine lab tests to monitor health include:

• Complete blood count (CBC).
• Urine test.
• Tests to monitor the functioning of organs.

Pain is sometimes a chronic problem for people with sickle cell disease. Your doctor or a pain treatment specialist can help you develop pain management skills. These skills include distraction, guided imagery, deep breathing, relaxation, and positive self-talk.

You can sometimes treat mild pain with pain medicines while at home. But call your doctor or go to the hospital if your pain is not controlled.

Severe episodes of prolonged erection of the penis (priapism) need evaluation by your doctor. Treatment may include fluids (hydration), pain medicines, treatment by a urologist, and blood transfusions.

If your child with sickle cell disease is at high risk for a stroke, your doctor may recommend blood transfusions, which may reduce this risk.

Acute chest syndrome may develop after a painful event or another illness and can be life-threatening. Early treatment is very important and may include oxygen, pain medicines, antibiotics, and transfusions.

You may not notice vision problems until damage has begun. Have your child's eyes checked when he or she is a newborn and again at all routine well-child visits.⁷ And get routine eye exams as an adult. Try to go to a doctor who specializes in eye problems (ophthalmologist).

People with sickle cell disease should avoid contact with anyone suspected of having fifth disease, which is caused by parvovirus. Parvovirus can cause the body to temporarily stop making blood cells, a severe life-threatening problem in someone with sickle cell disease. Aplastic anemia can develop as a result of a shortage of red blood cells. It can come on suddenly and is life-threatening if not treated.

Find more home treatment information for sickle cell disease at:

• Home treatment for pain.
• Home treatment for priapism.
• General health tips.

Treatment if the condition gets worse

Treatment for severe cases of sickle cell disease may include:

• Hydroxyurea medicine.
• Blood transfusions.

Organ failure can affect any part of the body in a person who has sickle cell disease. Treatment may include transfusions, medicines, and surgery. Surgery options include:

• Removal of the spleen (splenectomy), to prevent the trapping of too many red blood cells in the spleen (splenic sequestration).
• Removal of the gallbladder (cholecystectomy), to prevent problems caused by gallstones.
• Fluid drainage from the penis in cases of severe priapism.
• Hip replacement, if the tissue in the hip breaks down and dies because it doesn't get enough blood (osteonecrosis).

Identifying children at risk and treating them with blood transfusions may prevent strokes and other nervous system problems. A child or adult with sickle cell disease who has a stroke needs immediate medical help including medicines and transfusions.

What To Think About

Pregnant women who have sickle cell disease need specialized medical care.

A series of blood transfusions is the treatment of choice to prevent strokes and treat other aspects of this disease. But transfusions can cost a lot. And if you get a lot of them, you could develop antibodies that attack and destroy the donor blood. This is called alloimmunization. It occurs in about 1 out of 4 people with sickle cell disease who get frequent transfusions.³

People with sickle cell disease and their families face ongoing stress. A support network (such as doctors, extended family, friends, church, and counselors) can help ease stress and worry.

Painful events and serious complications of the disease can happen suddenly and unpredictably and can become life-threatening. Bouts of severe pain can last for hours to days and are difficult to treat. They're exhausting for caregivers as well as for the person in pain. For more information, see the topic Chronic Pain.

Prevention

Sickle cell disease is an inherited blood disorder that is not preventable. But a couple may meet with a genetic counselor before becoming pregnant to learn more about their chances of having a child with sickle cell disease. People whose ancestors were from Africa, India, the Middle East, the Mediterranean (Turkey, Italy, Greece), and some Latin American countries are more likely to inherit the gene that can cause sickle cell disease. In the United States, the disease mainly affects African Americans (1 out of 650) and Latin Americans (1 out of 1,000 to 1,400).⁴

Home Treatment

Home treatment for sickle cell disease includes steps to control pain and prevent complications of the disease. If you don't already have a home treatment plan, ask your doctor to help you develop one. Use this plan whenever symptoms are present. Your plan may include:

• Home treatment for pain.
• Home treatment for prolonged erection of the penis (priapism).
• General health tips.

Children with sickle cell disease need standard immunizations, such as pneumococcal and flu shots. Also, children younger than 5 need to take a daily antibiotic, such as penicillin, to prevent infection.⁵

Special needs of people living with sickle cell disease

You can help your child cope with special needs in school by:

• Making arrangements with teachers or a tutor to help your child keep pace with classmates when illness causes absences from school.
• Explaining to teachers that children with sickle cell disease may need to use the bathroom more often than other kids. They also need more water than the other students. Not drinking enough water can raise the chance of a sickle cell crisis.
• Educating teachers and other school employees about the signs and symptoms of sickle cell disease that need urgent medical care. Written instructions will help school personnel know what to do and who to call in an emergency.

Children with sickle cell disease can usually exercise and play normally if they:

• Drink plenty of fluids before, during, and after exercise. Lack of fluids (dehydration) can cause cells to sickle.
• Get regular rest breaks during vigorous exercise.
• Stay warm. Exposure to cold air, wind, and water can trigger a painful event. Dress children in warm layers of clothing for cold-weather activities. Avoid swimming and playing in cold water.

Medications

Medicines that treat sickle cell disease include hydroxyurea and various pain medicines. Some of these medicines require a prescription. Others are available over-the-counter. Pain medicine may work best when combined with pain management skills, such as distraction, guided imagery, deep breathing, relaxation, and positive, encouraging self-talk.

Hydroxyurea is approved by the U.S. Food and Drug Administration (FDA) for treating sickle cell disease in adults. Hydroxyurea increases fetal hemoglobin production, which can decrease the severity of sickle cell disease and can prolong life for severely affected adults. Research suggests that hydroxyurea also works well for children. But long-term studies are needed before hydroxyurea is routinely suggested for children.

Medication Choices

Hydroxyurea

Pain medicines

What To Think About

Hydroxyurea

• Hydroxyurea doesn't cure sickle cell disease, but it can reduce the number of serious sickling complications.
• Doctors recommend hydroxyurea treatment only for adults who have three or more painful events each year. Using it requires frequent blood tests and doctor visits. Most people who take this medicine have fewer pain events and acute chest events, and may also live longer.

Pain medicines

• Treatment for sickle cell disease pain varies depending on how bad the pain is and how long the pain lasts. Medicines that treat sickle cell disease pain include over-the-counter pain relievers such as ibuprofen and prescription opioids such as codeine.
• An increasing number of doctors and researchers recommend aggressive and continuous opiate pain medicine for severe painful events until the pain goes away.⁸

Sickle cell pain is often undertreated because:

• Some doctors underestimate the intensity of painful events.
• Some parents, doctors, and adults with sickle cell disease fear that use of opiate medicines (such as codeine and morphine) will lead to drug addiction. Research suggests that drug addiction is no greater among people with sickle cell disease than it is in the general population.⁸ It's important to use these medicines under careful medical supervision.

Surgery

There is no surgical cure for sickle cell disease.

Some sickle cell disease complications are treated by surgery. These surgeries involve:

• Removing the spleen (splenectomy), to prevent the trapping of too many red blood cells in the spleen (splenic sequestration).
• Removing the gallbladder (cholecystectomy), to prevent problems caused by gallstones.
• Draining fluid from the penis in cases of severe priapism.
• Hip replacement, if the tissue in the hip breaks down and dies because it doesn't get enough blood (osteonecrosis).

Other Treatment

Blood transfusions can treat some complications of sickle cell disease and prevent others. Adding healthy cells to the bloodstream can reverse some of the damage that sickled cells cause. Severe anemia, stroke, and acute chest syndrome are conditions that blood transfusions treat. Transfusions may also help prevent stroke or heart failure. But there is a downside to this practice: repeat transfusions can cause complications. So doctors weigh benefits and risks before suggesting this procedure.

Other Treatment Choices

Blood transfusions (regular or emergency)

What To Think About

Regular blood transfusions for sickle cell disease can cause iron buildup in the body, which requires daily treatment (iron chelation) and close monitoring.

Bone marrow transplant for children is currently the only procedure that can actually cure sickle cell disease. But bone marrow transplants are seldom used because few children meet the criteria. Donors are almost always siblings, so the lack of matching bone marrow donors is a factor. Cost is also a barrier.

More than 90% of children survive this type of transplant. After 11 years, nearly 85% of those children remain free of sickle cell disease.⁵ The main complication from the transplant is when the body rejects the bone marrow (graft-versus-host disease). This procedure is still considered experimental.

Folic acid supplements are often a necessary part of the diet for people with sickle cell disease, particularly if you aren't eating enough folate-rich leafy vegetables (such as spinach).

Studies continue to test new therapies to decrease cell sickling and improve blood flow.

Other Places To Get Help

Organizations

Related Information

• Blood Transfusion
• Caregiver Tips
• Chronic Pain
• Genetic Test
• Genetics
• Immunizations
• Sickle Cell Test
• Stress Management

References

Citations

1. Gladwin MT, et al. (2004). Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. New England Journal of Medicine, 350(9): 886–95.
2. Hirst C, Wang WC (2001). Blood transfusion for preventing stroke in people with sickle cell disease. Cochrane Database of Systematic Reviews (1). Oxford: Update Software.
3. Steinberg MH (2008). Sickle cell disease and associated hemoglobinopathies. In L Goldman, D Ausiello, eds., Cecil Medicine, 23rd ed., pp. 1217–1226. Philadelphia: Saunders Elsevier.
4. Wang WC (2004). Sickle cell anemia and other sickling syndromes. In JP Greer et al., eds., Wintrobe's Clinical Hematology, 11th ed., pp. 1264–1311. Philadelphia: Lippincott Williams and Wilkins.
5. National Heart, Lung, and Blood Institute, National Institutes of Health (2002). The Management of Sickle Cell Disease (NIH Publication No. 02-2117). Available online: http://www.nhlbi.nih.gov/health/prof/blood/sickle/.
6. Goldstein LB, et al. (2006). Primary prevention of ischemic stroke: A guideline from the American Heart Association/American Stroke Association Stroke Council. Stroke, 37(6): 1583–1633.
7. American Academy of Pediatrics, et al. (2003, reaffirmed 2007). Policy statement: Eye examination in infants, children, and young adults by pediatricians. Pediatrics, 111(4): 902–907.
8. Committee on Genetics, American Academy of Pediatrics (2002). Health supervision for children with sickle cell disease. Pediatrics, 109(3): 526–535.

Other Works Consulted

• Brawley OW, et al. (2008). National Institutes of Health consensus development conference statement: Hydroxyurea treatment for sickle cell disease. Annals of Internal Medicine, 148(12): 932–938.
• De Montalembert M (2008). Management of sickle cell disease. BMJ, 337(a1397): 626–630.
• Furie B, et al. (2003). Red blood cell disorders. In Clinical Hematology and Oncology: Presentation, Diagnosis, and Treatment, pp. 464–465. Philadelphia: Churchill Livingstone.
• Hillman RS, et al. (2005). Hemoglobinopathies. In Hematology in Clinical Practice, 4th ed., pp. 80–94. New York: McGraw-Hill.
• Hirst C, Owusu-Ofori S (2002). Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease. Cochrane Database of Systematic Reviews (3). Oxford: Update Software.
• Jones AP, et al. (2001). Hydroxyurea for sickle cell disease. Cochrane Database of Systematic Reviews (2). Oxford: Update Software.
• Lanzkron S, et al. (2008). Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease. Annals of Internal Medicine, 148(12): 939–955.
• Meremikwu MM (2007). Sickle cell disease, search date August 2006. Online version of BMJ Clinical Evidence: http://www.clinicalevidence.com.
• Price EA, Schrier SL (2008). Hemoglobinopathies and hemolytic anemias. In DC Dale, DD Federman, eds., ACP Medicine, section 5, chap. 4. Hamilton, ON: BC Decker.

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