Sickle Cell Disease

What is sickle cell disease?
Sickle cell disease is an inherited blood disorder characterized by defective hemoglobin. It affects millions of people throughout the world and approximately 72,000 people in the US. It is present in one in every 500 African-American births.

Normal hemoglobin cells are smooth and round, allowing for ease in moving through blood vessels. Sickle cell hemoglobin molecules are stiff and form into the shape of a sickle or a scythe. They tend to cluster together, and cannot easily move through blood vessels. The cluster causes a blockage and stops the movement of oxygen-carrying blood.

Sickle cells die after about 10 to 20 days, unlike normal hemoglobin cells, which live for up to 120 days. This results in a chronic short supply of red blood cells, which causes anemia.

The most common variations of the sickle cell gene include the following:

• Sickle cell trait
  The person is carrying the defective gene, HbS, but also has some normal hemoglobin, HbA. This is referred to as HbAS. Persons with sickle cell trait are usually without symptoms of the disease. Mild anemia may occur. Under intense, stressful conditions, exhaustion, hypoxia (low oxygen), and/or severe infection, the sickling of the defective hemoglobin may occur and result in some complications associated with the sickle cell disease.
  
  
• Sickle cell anemia
  The person has most or all of the normal hemoglobin (HbA) replaced with the sickle hemoglobin (HbS). This is referred to as HbSS. It is the most common and most severe form of the sickle cell variations. These persons suffer from a variety of complications due to the shape and thickness of the sickled cells. Severe and chronic anemia is also a common characteristic for children with HbSS.
  
  
• Sickle cell - hemoglobin C disease
  The person has both HbS and HbC. This is often referred to as HbSC. Hemoglobin C causes red blood cells, called target cells, to develop. Having just some hemoglobin C and normal hemoglobin, a person will not have any symptoms of anemia. However, if the sickle hemoglobin S is combined with the target cell, some mild to moderate anemia may occur. These persons often suffer some of the complications associated with HbSS, sickle cell disease, but to a milder degree. Vasoocclusive crises (the flow of blood is blocked because the sickled cells have become stuck in the blood vessels), organ damage from repeated sickling and anemia, and high risk for infection are all similar traits for HbSS and HbSC.
  
  
• Sickle cell - hemoglobin E disease
  This variation is similar to sickle cell-C disease except that an element has been replaced in the hemoglobin molecule. This variation is often also seen in Southeast Asia populations. Some persons with hemoglobin E disease are without symptoms. However, under certain conditions, such as exhaustion, hypoxia, severe infection, and/or iron deficiency, some mild to moderate anemia may occur.
  
  
• Hemoglobin S-beta-thalassemia
  This involves an inheritance of both the thalassemia and sickle cell genes. The disorder produces symptoms of moderate anemia and many of the same conditions associated with sickle cell disease, to a milder degree.

All forms of sickle cell disease can exhibit the complications associated with the disease. Persons with HbSS, however, are the most severely affected.

Who is affected by sickle cell disease?
Sickle cell disease primarily affects those of African descent and Hispanics of Caribbean ancestry, but the trait has also been found in those with Middle Eastern, Indian, Latin American, Native American, and Mediterranean heritage.

It has been estimated that over 72,000 people in the US are affected by the disease. Millions worldwide suffer complications from sickle cell disease. It is present in one in every 500 African-American births. Two million African-Americans, or one in 12, have the sickle cell trait.

What causes sickle cell disease?
Sickle cell disease is an inherited disease caused by a genetic mutation. Genes are found on structures in the cells of our body called chromosomes. There are normally 46 total, or 23 pairs, of chromosomes in each cell of our body. The 11th pair of chromosomes contains a gene responsible for normal hemoglobin production.

A mutation or error in this gene is what causes sickle cell disease. This mutation is thought to have originated in areas of the world where malaria was common, since people with sickle trait do not get malaria. The sickle trait actually protects them from the parasite that causes malaria, which is carried by mosquitoes. Malaria is most often seen in Africa and in the Mediterranean area of Europe.

Children who inherit the genetic mutation from both parents will have sickle cell disease. Children who inherit the mutation from only one parent will not have the disease, but will carry the trait for it and can pass it on to their children.

What are the symptoms of sickle cell disease?
The following is a list of symptoms and complications associated with sickle cell disease. However, each individual may experience symptoms differently. Symptoms and complications may include, but are not limited to, the following:

• anemia - the most common symptom of all the sickle cell diseases. In sickle cell disease, red blood cells are produced but then become deformed into the sickle shape, which causes red blood cells to lose their oxygen carrying capacity. The body subsequently becomes dehydrated, or with a fever. This sickle shape makes the cells stiff and sticky causing them to become stuck in the vessels, destroyed by the spleen, or simply die because of their abnormal function. The decrease in red blood cells causes anemia. Severe anemia can make a person pale and tired, and makes the person's ability to carry oxygen to the tissues more difficult. Healing and normal growth and development may be delayed because of chronic anemia.
  
  
• pain crisis, or sickle crisis - when the flow of blood is blocked to an area because the sickled cells have become stuck in the blood vessel. These are also called "vasoocclusive crises." The pain can occur anywhere, but most often occurs in the chest, arms, and legs. Painful swelling of the fingers and toes, called dactylitis, can occur in infants and children under 3 years of age. Priapism is a painful sickling that occurs in the penis. Any interruption in blood flow to the body can result in pain, swelling, and possible death of the surrounding tissue not receiving adequate blood and oxygen.
  
  
• acute chest syndrome - when sickling is in the chest. This can be a life-threatening complication of sickle cell disease. It often occurs suddenly, when the body is under stress from infection, fever, or dehydration. The sickled cells stick together and block the flow of oxygen in the tiny vessels in the lungs. It resembles pneumonia and can include fever, pain, and a violent cough. Multiple episodes of acute chest syndrome can cause permanent lung damage.
  
  
• splenic sequestration (pooling) - crises are a result of sickle cells pooling in the spleen. This can cause a sudden drop in hemoglobin and can be life threatening if not treated promptly. The spleen can also become enlarged and painful from the increase in blood volume. After repeated episodes of splenic sequestration, the spleen becomes scarred, and permanently damaged. Most children, by the age of 8 years old, do not have a functioning spleen either from surgical removal, or from repeated episodes of splenic sequestration. The risk of infection is a major concern of children without a functioning spleen. Infection is the major cause of death in children under the age of 5 years in this population.
  
  
• stroke - another sudden and severe complication of persons with sickle cell disease. The misshapen cells can block the major blood vessels that supply the brain with oxygen. Any interruption in the flow of blood and oxygen to the brain can result in devastating neurological impairment. Having had one stroke, a person is 60 percent more likely to have a second and third stroke.
  
  
• jaundice, or yellowing of the skin, eyes, and mouth - a common sign and symptom of sickle disease. Sickle cells do not live as long as normal red blood cells and, therefore they are dying more rapidly than the liver can filter them out. Bilirubin (which causes the yellow color) from these broken down cells builds up in the system causing jaundice.

Any and all major organs are affected by sickle cell disease. The liver, heart, kidneys, gallstone, eyes, bones, and joints can suffer damage from the abnormal function of the sickle cells and their inability to flow through the small blood vessels correctly. Problems may include the following:

• increased infections
• leg ulcers
• bone damage
• early gallstones
• kidney damage and loss of body water in the urine
• eye damage

The symptoms of sickle cell disease may resemble other blood disorders or medical problems. Always consult your physician for a diagnosis.

How is sickle cell disease diagnosed?
In addition to a complete medical history and physical examination, diagnostic procedures for sickle cell disease may include blood tests and other evaluation procedures. Many states provide routine newborn screening blood tests in order to begin proper treatment as soon as possible.

Early diagnosis is essential in providing proper preventative treatment for some of the devastating complications of the disease.

A hemoglobin electrophoresis is a blood test that can determine if a person is a carrier of a specific sickle cell trait, or has any of the diseases associated with the sickle cell gene.

Treatment for sickle cell disease:
Specific treatment for sickle cell disease will be determined by your physician based on:

• your age, overall health, and medical history
• extent of the disease
• your tolerance for specific medications, procedures, or therapies
• expectations for the course of the disease
• your opinion or preference

Early diagnosis and prevention of complications is critical in sickle cell disease treatment. Treatment may include:

• pain medications (for sickle cell crises)
  
  
• drinking plenty of water daily (eight to 10 glasses) or receiving fluid intravenously (to prevent and treat pain crises)
  
  
• blood transfusions
  For anemia and to prevent stroke, blood transfusions may be used. Transfusions are also used to dilute the HbS with normal hemoglobin to treat chronic pain, acute chest syndrome, splenic sequestration, and other emergencies.
  
  
• penicillin (to prevent infections)
  
  
• folic acid (to help prevent severe anemia)
  
  
• hydroxyurea
  Hydroxyurea is a medication that has recently been developed that may help reduce the frequency of pain crises and acute chest syndrome. It may also help decrease the need for frequent blood transfusions. The long-term effects of the medication, however, are unknown.
  
  
• bone marrow transplant
  Bone marrow transplant has been effective in curing some persons with sickle cell disease; the decision to undergo this procedure is based on the severity of the disease and ability to find a suitable bone marrow donor. These decisions need to be discussed with your physician.