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Sickle Cell Anemia

Thursday, Oct 23, 2008 | Updated 11:15 AM EST

Sickle cell anemia is a painful, inherited condition in which the red blood cells become abnormally shaped. It may lead to pain or a number of other serious complications including stroke, life–threatening infection or end-organ damage.

Red blood cells transport vital oxygen to the limbs and organs. These cells are normally disc–shaped. In people with sickle cell anemia, a large number of these red blood cells become sickle- or crescent–shaped.

Hemoglobin, a protein molecule present in all red blood cells, is responsible for transporting oxygen from the lungs to the tissues around the body. However, in people with sickle cell anemia, a sickle–shaped red blood cell develops as a result of the presence of an abnormal hemoglobin called hemoglobin S. Normally red blood cells contain hemoglobin A. But with hemoglobin S, there is a reduction in the amount of oxygen transported in the red blood cells.

As a result of this reduced oxygen, the cells change shape. These sickle-shaped cells are harmful because they often get stuck in small blood vessels, obstructing the flow of blood. This can lead to a number of complications, including recurrent episodes of pain known as asvaso-occlusive sickle cell crises.

These structurally abnormal cells also become very fragile and begin to be broken down prematurely, at a rate faster than the body can replace them. As a result, patients with sickle cell anemia often have a lower-than-normal number of red blood cells in their blood, condition called anemia. This can lead to a number of symptoms including fatigue, jaundice (yellowing of skin and eyes) and shortness of breath.

Sickle cell anemia can affect only someone who has inherited hemoglobin S from both parents. A person who inherits hemoglobin S from only one parent can have sickle cell trait (AS). Known as carriers, these people with sickle cell trait usually have no symptoms. They can, however, pass the trait onto their children.

To determine if a person has sickle cell anemia or sickle cell trait, physicians may order a number of blood tests (e.g., hemoglobin electrophoresis, sickle cell test). Newborns are routinely screened for the abnormal gene in many states. Adults, older children and fetuses can also be screened.

According to the Sickle Cell Disease Association of America, there are approximately 70,000 people living with the sickle cell anemia in the United States. Most of these patients are African American and Hispanic.

Currently, bone marrow transplant is the only cure for sickle cell anemia. The procedure, however, is risky, and it is often difficult to find a suitable donor. When a bone marrow transplant is not an option, the focus of treatment is on relieving pain and preventing crises and other complications.

Common treatment methods include medication (including those to control pain and reduce the number of crises), vaccinations and blood transfusions. A number of additional treatment methods are also being studied that may cause the body to produce more hemoglobin, such as the use of hydroxyurea.

In the past, people with sickle cell anemia often died between the ages of 20 and 40, usually because of organ failure. However, medical advancements have enabled most sickle cell patients to live well into their 40s and 50s.

Couples in which both partners carry the sickle cell gene may be able to lower their risk of having a child with sickle cell anemia with an in vitro fertilization technique known as preimplantation genetic diagnosis. This procedure allows physicians to implant eggs that are free of the defective gene into a woman for development.

About sickle cell anemia

Sickle cell anemia is an inherited blood disorder. It affects the red blood cells resulting in pain and a number of other complications.

Sickle cell anemia is a form of anemia, a condition in which there is a lower than normal number of red blood cells in the blood. Red blood cells normally live for three to four months. People with sickle cell anemia have abnormal cells known as sickle cells, which are fragile and begin to break down after 10 to 20 days. This often results in a shortage of red blood cells because it is difficult for the body to produce enough replacements.

Red blood cells are produced in the bone marrow, the soft inner component of bones. They contain hemoglobin, an iron–rich proteinmolecule that picks up oxygen from the lungs and releases it to the tissues as blood travels through the body. In healthy individuals, the body produces normal hemoglobin (hemoglobin A). In people with sickle cell anemia, red blood cells mostly contain an abnormal form of hemoglobin know as hemoglobin S. Hemoglobin S reduces the amount of oxygen in the cells. As a result, the shape of the cells becomes distorted.

Red blood cells are normally disc–shaped, flexible and smooth. This allows them to travel easily through the blood vessels of the body. In people with sickle cell anemia, however, red blood cells undergo a structural change and become crescent shaped under reduced oxygen conditions. The cells are named after the sickle, a crescent–shaped tool used to cut wheat. Red blood cells containing hemoglobin S can change from normal shape to sickle shape and back again until they become permanently sickle–shaped.

Sickle cells are also rigid and sticky. As a result, they can get stuck while traveling through small blood vessels. This can slow or block the flow of blood through the body. Clogged blood vessels can lead to a number of complications, including recurrent episodes of pain known as crises, which is the most common manifestation of this disease.

Crises occur in most people with sickle cell anemia at some point during their lifetime. Signs usually develop during infancy or childhood. Typically, pain lasting anywhere from a few hours to weeks can occur in the back, ribs, and limbs. Pain may also develop in the chest, abdomen and joints. In severe cases, hospitalization may be required so the patient may receive pain medications and intravenous (I.V.) fluids.

Though some patients experience a crisis once every few years, others may have several episodes a year. After repeated crises, a patient may develop damage to the kidneys, lungs, bone, eyes and central nervous system. These crises can be precipitated by infections, which should be excluded. Opioid pain medications may be used to treat moderate to severe pain.

Common forms of crisis include:

Hemolytic crisis. This crisis results from the rapid destruction of damaged red blood cells.
Splenic sequestration crisis. This crisis is the result of red blood cells suddenly becoming trapped in the spleen, resulting in a enlarged spleen and low blood volume. Urgent medical care is necessary.
Aplastic crisis. This crisis is the result of infection (caused by the parvovirus B19) causing the bone marrow to stop producing red blood cells. It is characterized by a sudden decrease in hemoglobin counts, requiring urgent blood transfusion.

Sickle cell anemia can lead to a number of other complications, some of which are life–threatening. Possible complications include:

Stroke. A potentially fatal event in which the flow of oxygen–rich blood to the brain is reduced. In a person with sickle cell anemia, a stroke may occur as the result of sickle cells obstructing blood flow to the brain. Common signs of stroke include weakness or numbness in the limbs, especially on one side of the body, sudden difficulty speaking or swallowing, or alteration of consciousness.They occur more commonly in children younger than 10 years old.

In 2005, scientists unveiled a genetic test they described as 98 percent accurate in predicting strokes in people who have sickle cell anemia. The test detects variations in genes called single nucleotide polymorphisms (SNPs).

Acute chest syndrome. A life–threatening condition, acute chest syndrome causes chest pain, fever and breathing difficulty. It is the result of lung infection or sickle cells becoming trapped in the lungs and can be indistinguishable from pneumonia. Recurrent episodes can cause lung damage.

Organ damage. As blood travels throughout the body it delivers oxygen to the organs. When sickle cells block blood flow through the blood vessels they deprive the organs of the oxygen they need. This may result in damage to nerves and organs including the kidneys, liver and spleen. In some cases, organ damage may be fatal. Necrosis of the hip and shoulder joints may occur, causing considerable disability, and may require joint replacement surgery (arthroplasty).
Blindness. In people with sickle cell anemia, sickle cells can obstruct the tiny blood vessels of the eyes. This can damage the retina (the component of the eye which processes visual images) and may lead to blindness.
Ulcers. People with sickle cell anemia may develop open sores on their legs. Known as ulcers, these sores are the result of sickle cells blocking blood flow which nourishes the skin. This results in death of the skin cells and causes sores to develop.

Gallstones. Bilirubin is a substance produced from the breakdown of red blood cells. People with sickle cell anemia may have high levels of bilirubin in their blood, which can lead to gallstones. This may be present in up to 50 percentof adults with this disease.
Impotence. In men, sickle cell anemia can lead to priapism (painful erections). This is the result of sickle cells preventing the blood from flowing out of an erect penis. According to the National Institutes of Health (NIH), about 10 to 40 percent of men with sickle cell anemia experience priapism. The condition can damage the penis and cause impotence.
Infection. Sickle cells can cause damage to the spleen, an organ responsible for fighting infection. As a result, people with sickle cell anemia are at an increased risk of infection including pneumonia, cholecystitis (inflammation of the gallbladder), osteomyelitis (bone infection), and urinary tract infection.

According to the Sickle Cell Disease Association of America there are approximately 1,000 babies born with the disease each year and more than 70,000 people living with the disease in the United States. Although complications such as infection and organ damage can be fatal, most patients live into their 40s and 50s, whereas in the past the life expectancy was often between 20 and 40.

In addition, there are also other sickle cells diseases (SCDs), or hemoglobinopathies, in which symptoms may resemble those of sickle cell anemia but are generally milder. These related disorders include hemoglobin C disease, hemoglobin SC disease, sickle beta-plus thalassemia and sickle beta-zero thalassemia. The National Institutes of Health estimates that 80,000 Americans have some form of sickle cell disease. It describes SCD as the nation's most common inherited blood disorder.

Risk factors and causes of sickle cell anemia

Sickle cell anemia is an inherited disorder. Known as an autosomal recessive trait, the disease can occur only in someone who is homozygous: has inherited hemoglobin S from both parents. A person who inherits hemoglobin S from one parent and normal hemoglobin (hemoglobin A) from the other parent will have sickle cell trait (AS), a heterozygous condition.

In people with the sickle cell trait, the body produces hemoglobin A as well as hemoglobin S. However, there is always more hemoglobin A than hemoglobin S. Although their blood may contain some sickle cells, people with the sickle cell trait are generally healthy and do not usually experience signs and symptoms of sickle cell anemia. They can, however, pass the defective gene onto their children. The Sickle Cell Disease Association of America estimates that 2.5 millionAmericans havethe sickle cell trait.

According to the National Heart, Lung and Blood Institute, a child born to two people with the sickle cell trait has:

A 25 percent chance of inheriting two sickle cell genes and having sickle cell anemia
A 25 percent chance of inheriting two normal genes and not having the disease or the trait
A 50 percent chance of inheriting one normal gene and one sickle cell gene, and having the sickle cell trait

According to the Sickle Cell Disease Association of America, when one parent has sickle cell anemia and the other has sickle cell trait, there is a 50 percent chance with each pregnancy that the child will have either the disease or the trait.

Sickle cell anemia affects millions of people around the world. However, the disease is more common among certain ethnic groups. The sickle cell trait is commonly found in people of African, Hispanic (e.g., South America, Cuba, Central America), Mediterranean (e.g., Turkey, Greece, Italy), Middle Eastern and Indian descent. In the United States, the disease most often affects African Americans and Hispanics.

According to the National Heart, Lung and Blood Institute, approximately one in 12 African Americans carry the sickle cell trait, and the disease occurs in about one in every 600 African American births. In comparison, the disease occurs in one of every 1,000 to 1,400 Hispanic American births.

Signs and symptoms of sickle cell anemia

Sickle cell anemia can cause a variety of signs and symptoms. Common signs and symptoms include:

Paleness (pallor)
Jaundice (yellowing of the eyes and skin)
Fatigue
Swollen hands and feet (hand–foot syndrome)
Loss of breath
Rapid heart rate
Stunted growth/delayed puberty
Frequent infection
Ulcers on the lower legs
Fever

Patients with sickle cell anemia may also experience pain as the result of sickle cells blocking blood flow through the blood vessels. The pain may be acute, chronic or a combination of both. Pain commonly experienced by people with the disease includes:

Bone pain and joint pain
Abdominal pain
Chest pain
Back pain
Arm pain
Leg pain

Additional signs and symptoms include:

Bloody urine (hematuria)
Frequent urination (polyuria)
Excessive thirst (polydipsia)
Painful erection (priapism)
Poor vision/blindness

Although sickle cell anemia is present at birth, most people do not show symptoms of the condition until four months of age. Some people with the condition have mild symptoms, while others have severe symptoms that require hospitalization. People with the sickle cell trait do not usually develop any signs and symptoms of sickle cell anemia. Areas with low oxygen, however, may trigger symptoms in people with the trait. This includes areas of high altitude such as mountains and flying in airplanes.

Diagnosis methods for sickle cell anemia

Many people carrying the sickle cell trait do not know that they have it. As a result, most states routinely screen all newborns for the disease. Screening is available by request in all other states. These tests reveal whether the infant has the disease or carries the sickle cell trait. Diagnosis of the disease in infants is important because it ensures that the babies receive necessary treatment immediately.

Older children and adults can also be screened for sickle cell anemia and sickle cell trait. In adults, the required blood sample is usually drawn from a vein in the arm. In babies and young children, blood may be collected from a finger or heel prick. It is also possible to detect sickle cell anemia before birth by testing a sample of amniotic fluid (the fluid surrounding the baby in the womb) or tissue collected from the placenta.

The sickle cell test is a blood test used to determine whether a patient has the abnormal hemoglobin that causes sickle cell anemia (hemoglobin S) in their blood.A deoxygenation agent is added to the blood sample. When 25 percent or more of the hemoglobin is hemoglobin S, the red blood cells will structurally change into a sickle (crescent) shape. This occurrence indicates that the patient either has sickle cell anemia or has sickle cell trait.

In order to determine whether a patient has the disease or just carries the defective gene, the percentage of hemoglobin S in the blood has to be measured. Patients with sickle cell trait will have a small percentage of hemoglobin S in the blood, whereas people with sickle cell anemia will have a significantly larger percentage of the abnormal hemoglobin.

To determine what types of hemoglobin are present in the blood, physicians will order a hemoglobin electrophoresis. During this test, electrical charges are sent through a solution of hemoglobin. Because different types of hemoglobin move different distances in response to electric charge, the test can be used to differentiate normal hemoglobin (hemoglobin A) from hemoglobin S. Patients with significant levels of abnormal hemoglobin S may be diagnosed with sickle cell anemia in this manner.

Patients diagnosed with sickle cell anemia will be tested for anemia. A complete blood count will be ordered to determine the number of red blood cells in the blood. A number of additional tests may be ordered to check for other potential complications of the disease.

Children and adults with the disease may be referred to a hematologist, a physician who specializes in blood diseases. Carriers of the sickle cell trait may be referred to a genetic counselor, a professional who specializes in genetic diseases. Such counselors can provide a carrier with information regarding their risk of having a child with sickle cell anemia. They can also explain treatment options, preventive measures and reproductive choices.

Treatment options for sickle cell anemia

Bone marrow transplant is the only known cure for sickle cell anemia. Currently, however, it is recommended only for patients with severe symptoms and complications. The procedure carries many risks and is not always successful. In some cases the patient's body may reject the bone marrow. It is also difficult to find suitable donors.

Before undergoing a bone marrow transplant, chemotherapy or radiation is used to destroy the recipient's bone marrow. Surgery is then performed to remove healthy bone marrow from the matched donor. The collected bone marrow is placed in the patient's body through a transfusion. As a result, the healthy bone marrow may begin to produce normal blood cells.

A number of other treatment options are available. These treatments do not cure sickle cell anemia, but focus on relieving the symptoms and possibly preventing crises and other complications.

Common treatment options include:

Medications. A number of medications may be used to reduce pain and prevent complications including:

Antibiotics. People with sickle cell anemia are vulnerable to infection. As a result, penicillin is often given to babies with sickle cell anemia when they are 2 to 4 months old. The drug is continued until the patient reaches 5 years of age. This helps prevent pneumonia and other life–threatening infections. Antibiotics may also be prescribed to adults with sickle cell anemia to treat infections.
Folic acid. In patients with this disease, a supplemental dose of folic acid should be taken because of chronic destruction of red blood cells.
Pain relievers. Patients may be able to relieve mild crisis–related pain with over–the–counter pain medications. Physicians may prescribe stronger pain medications for more moderate to severe pain. Pain relievers commonly used with sickle cell anemia include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids.
Hydroxyurea. Normally used to treat cancer, this drug may reduce the frequency of crises and acute chest syndrome when taken daily. It also reduces the need for blood transfusions. The drug appears to work by stimulating the production of fetal hemoglobin. Found in newborns, fetal hemoglobin prevents the formation of sickle cells. There is some concern, however, that use of this drug increases the risk of tumors or leukemia. Patients should discuss these risks with their physician. This drug has not been approved for use in children.

Vaccinations. Patients benefit from receiving regular vaccinations because they help prevent contracting infections. Infants should receive all of the recommended vaccinations (e.g., measles, mumps, and rubella). Children with the sickle cell should receive an annual influenza shot, as well as vaccinations for pneumonia, meningitis and hepatitis. Adult patients should have annual influenza vaccinations and regular pneumonia vaccinations.
Blood transfusions. During this procedure, red blood cells removed from donated blood are given intravenously to the patient. It is used to relieve anemia, which can cause jaundice and fatigue, by increasing the number of normal red blood cells. It may also be used to lower a patient's risk of stroke. Recent research suggests that the 10 percent of sickle cell patients who are at high risk of stroke because of narrow blood vessels in the brain may need a lifetime of transfusions to lower their risk.
Supplemental oxygen. Administered through a breathing mask, supplemental oxygen adds oxygen to the blood and improves breathing. It may be used during episodes of acute chest syndrome or a sickle cell crisis.

Complications are treated as they develop. Treatments for common complications include:

Acute chest syndrome. This condition may be treated with oxygen therapy, transfusions, antibiotics and pain medications.
Hand–foot syndrome. This condition may be treated with pain medication and fluids.
Leg ulcers. These sores may be treated with cleansing solutions and zinc oxide. Treatment may also include pain medication, bedrest and keeping the leg raised to reduce swelling. In some cases, skin grafts may be necessary.
Stroke. Depending on the type and severity of the stroke, patients may require surgery, medications or rehabilitation, such as physical therapy and occupational therapy. As noted above, blood transfusions may reduce the risk of stroke.
Kidney disease. This complication may be treated with dialysis or a kidney transplant if end-stage.
Priapism. Men experiencing priapism (painful erections) may need medications or surgery.
Vision problems. Corrective lens, surgical procedures or low-vision rehabilitation may be used to treat eye or vision problems.
Gallstone disease. Patients with gallstone disease may require surgery to remove the gallbladder.
Damaged spleen. This condition may be treated with surgery (splenectomy).

There are a number of steps a physician may recommend that patients take to maintain their health and prevent crises. These measures may include:

Taking supplements of folic acid. Bone marrow requires folic acid for the production of red blood cells. People with sickle cell anemia may benefit from taking folic acid supplements daily to boost their red blood cell production.
Eating a well–balanced diet. Good nutrition can provide the body with the vitamins needed to produce red blood cells.
Drinking plenty of water. Drinking water allows patients to stay hydrated. This maintains dilution of the blood, which reduces the likelihood that sickle cells will form.
Avoiding extreme temperatures. Patients with sickle cell anemia should avoid exposure to extreme cold or heat because such temperatures may cause sickle cells to form.
Limiting exposure to the sun. Too much solar exposure can cause dehydration, a condition that increases the likelihood that sickle cells will form.
Avoiding and reducing stress. Patients should avoid stress because it can cause tissue deoxygenation and trigger a sickle crisis. Stress related to living with a chronic, life–threatening disease may be reduced by attending counseling and support groups. These outlets may help the patient relieve stress by sharing common experiences.
Exercising regularly. People with sickle cell anemia may benefit from moderate exercise. Patients should discuss exercise with their physician prior to starting as excessive exercise can be harmful. Strenuous exercise, particularly when the spleen is enlarged, can deprive the tissues of oxygen (cause deoxygenation). Low oxygen levels may lead to a crisis. A crisis may also be triggered by dehydration, overheating or exhaustion caused by overactivity.

Also, individuals with an enlarged spleen should not engage in contact sports or activities that could rupture the spleen.
Avoiding environments low in oxygen content. Environments with low oxygen content can lead to tissue deoxygenation and cause a crisis. To avoid complications, patients should avoid high altitudes and fly only on airplanes with pressurized cabins. They should also avoid spending long periods of time under water.
Getting plenty of rest and sleep. Lack of sleep and rest can lead to the development of a sickle crisis.
Avoiding use of alcohol, tobacco and illegal drugs. Patients should avoid these substances because their use can trigger a sickle crisis.
Seeing a physician regularly. People with sickle cell anemia require regular healthcare visits. During these visits, physicians will measure the patient's red blood cell count and monitor the patient's general health. The physician will determine whether the patient is getting enough nutrition and physical activity. In many cases, individuals must be monitored by a hematologist (physician who specializes in blood disorders) or internist (physician who specializes in internal organs). Because sickle cell anemia can cause damage to the eyes, patients should also schedule regular visits to an ophthalmologist. Regular dental exams are also important to prevent infection and tooth loss.

Physician visits are particularly important for children with the disease. The National Heart, Lung and Blood Institute recommends that children under the age of 2 visit their physician every two or three months. After the age of 2, children should be scheduled for an appointment at least every six months. This will enable the physician to check the growth of the child and ensure that the young patient receives all of the vaccinations required.
Learning about the disease. Patients can benefit from learning about sickle cell anemia. Learning the signs of complications enables patients to seek early treatment when necessary. For example, patients can prevent serious infection by contacting their physician at the first sign of an illness.

Prevention methods for sickle cell anemia

Couples in which both partners carry the sickle cell gene may be able to lower their risk of having a child with sickle cell anemia.

During a procedure known as preimplantation genetic diagnosis, eggs are collected from a woman and sperm is taken from her male partner. The sperm is used to fertilize the eggs in a laboratory. Tests are then used to determine which eggs contain the sickle cell gene. Eggs that are found to be free of the defective gene are then implanted into the mother for development.

Although this form of in vitro fertilization improves a couple's chances of having a child with normal hemoglobin, the procedure is not always successful. In addition, the cost of the procedure can be excessive.

In couples who carry the sickle cell gene, there is no way to reduce the risk of having a child with sickle cell anemia through normal conception. These individuals should receive genetic counseling to thoroughly understand the risks involved with having children.

Ongoing research regarding sickle cell anemia

There is a great deal of research being conducted into sickle cell anemia, including clinical trials and scientific studies. Many studies are focused on developing more effective treatment methods. Areas of research include:

Gene therapy. Researchers are studying the idea that correcting the defective gene that causes sickle cell anemia and placing it into the bone marrow of people with the disease will result in production of normal hemoglobin. Additional studies are focusing on the possibility of deactivating the defective gene while reactivating the gene responsible for producing fetal hemoglobin.
Butyric acid. Butyric acid is a commonly used food additive. Researchers are investigating the possibility that the substance may increase the quantity of fetal hemoglobin in the blood.
Clotrimazole. Clotrimazole is an over–the–counter drug commonly used to treat fungal infections. Researchers are studying the drug to determine if it can reduce the number of sickle cells that form by preventing the loss of water from the red blood cells.
Nitric oxide. Nitric oxide is a gas that keeps the blood vessels open and reduces the adhesiveness of red blood cells. Researchers are investigating whether treatment with this gas would prevent the formation of sickle cells.
Hydroxyurea. Although the drug has been approved for the treatment of sickle cell anemia in adults, researchers are still trying to determine proper dosage for children.
Blood transfusions. Repeated blood transfusions can trigger iron overload, a disorder that cause organ damage. Researchers are trying to develop new methods of eliminating the accumulation of iron in the body.

Questions for your doctor

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about sickle cell anemia: