Also Known As
Sickle Cell Disease
SCD
This article was last reviewed on
This article waslast modified on
December 28, 2017.
What is sickle cell anemia?

Sickle cell anemia, also called sickle cell disease (SCD), is an inherited disorder that leads to the production of hemoglobin S (Hb S or Hgb S), an abnormal form of hemoglobin (hemoglobin variant). Hemoglobin is the iron-containing protein found inside red blood cells (RBCs) that carries oxygen from the lungs to all parts of the body and releases it to the body's cells and tissues.

Hemoglobin is made up of heme, which is the iron-containing portion, and globin chains, which are proteins. The globin protein consists of chains of amino acids, the "building blocks" of proteins. There are several different types of globin chains, named alpha, beta, delta, and gamma. Normal hemoglobin types include:

  • Hemoglobin A (Hb A): makes up about 95%-98% of hemoglobin found in adults; it contains two alpha (α) chains and two beta (β) protein chains, denoted as α2β2.
  • Hemoglobin A2 (Hb A2): makes up about 2%-3% of hemoglobin found in adults; it has two alpha (α) and two delta (δ) protein chains.
  • Hemoglobin F (Hb F, fetal hemoglobin): makes up to 1%-2% of hemoglobin found in adults; it has two alpha (α) and two gamma (γ) protein chains. It is the primary hemoglobin produced by the fetus during pregnancy. Shortly after a baby is born, Hb F is replaced by hemoglobin A as the predominant hemoglobin.

Hemoglobin variants – hemoglobin types other than normal hemoglobins F, A, and A2 – arise from either alpha or non-alpha (beta, gamma or delta) globin chains gene mutations. There are currently a few hundred hemoglobin variants identified and described. Hemoglobin Hb S, Hb C, Hb D and Hb E, resulting from mutations of beta-globin chains, are some of the most common hemoglobin variants.

Hemoglobin S results from a mutation affecting the beta-chain of hemoglobin. This mutation can affect either one of the beta chains of Hb A (heterozygote status or HS trait) or both of them (homozygote status or sickle cell disease).

  • A person who has one normal hemoglobin gene copy and one Hb S copy will produce about 40% hemoglobin S but will produce enough hemoglobin A (about 60%) so that he or she does not generally experience significant health problems. This single altered copy (heterozygous) can be passed on to the person's children.
  • When a person has two copies of the altered gene (homozygous), the person produces 80-90% hemoglobin S, no normal hemoglobin A, and has sickle cell anemia or sickle cell disease. Symptoms and complications of sickle cell disease may also be experienced by people who have one sickle cell gene copy and one gene copy for another hemoglobin variant (doubly heterozygous), such as hemoglobin C or the variants seen with beta thalassemia, a group of blood disorders resulting from gene mutations that decrease normal hemoglobin production. People with two copies of the Hb S gene (SS), and those with one copy and a variant (SC, S beta thalassemia, SD, SOArab), are all grouped under the term "sickle cell disease."
     

The hemoglobin S mutation results in hemoglobin that is less soluble within a red blood cell, which reduces the efficiency of oxygen exchange and can cause the formation of polymers in the cell during normal stages of oxygen transport. These polymers can change the shape of the RBC from a round disc to a characteristic sickle shape, especially in reduced oxygen environments. The altered shape limits the RBC's ability to flow smoothly throughout the body. The sickled cells can become stuck and obstruct small blood vessels, causing tissue damage.

Sickled RBCs are generally short-lived, only lasting about 10-20 days instead of the normal 120 days. To compensate, affected individuals must produce more red blood cells at a much faster rate and release them into the bloodstream earlier. They may become increasingly anemic when the body cannot keep up with the rapid RBC destruction, resulting in a condition known as hemolytic anemia, smaller than normal red cells (microcytosis), and an increased number of newly produced red cells called reticulocytes (reticulocytosis).

According to the National Heart, Lung, and Blood Institute, about 100,000 people in the U.S. have sickle cell anemia. It affects about one in 365 African Americans. About one in 13 African Americans are estimated to have sickle cell trait. Other people affected by this disease have Hispanic, southern European, Middle Eastern, and Asian Indian backgrounds.

Accordion Title
About Sickle Cell Anemia
  • Signs and Symptoms

    Sign and symptoms of sickle cell disease as well as their severity vary widely. Some people may have mild symptoms, while others may experience severe symptoms and frequent complications. Infants with sickle cell disease are typically normal at birth, developing symptoms in their first year as hemoglobin F is replaced with hemoglobin S as the dominant hemoglobin produced.

    People with sickle cell disease due to due two mutated gene copies of Hb S (SS) are more likely to have severe symptoms than those with one mutated gene copy Hb S (AS) or Hb C (SC). Those with sickle cell trait are generally healthy but may experience symptoms associated with sickle cell disease when they have lower levels of oxygen from intense exercise or dehydration, as with athletes, or from changes in altitude.

    Symptoms and complications of sickle cell disease may include:

    • Pain crises. Episodes of pain that can last for extended periods of time are the most common complication of sickle cell disease. The pain is associated with the narrowing or obstruction of small blood vessels (called vaso-occlusion), which reduces or prevents blood flow to the affected area and can cause tissue damage. The location of the pain and its duration can vary from crisis to crisis and can occur throughout the body, especially in the bones, joints, lungs, and belly. Pain and swelling in the hands and feet is often one of the first symptoms noticed in young children. Decreased oxygen, infection, dehydration, change in altitude, and temperature extremes can precipitate a pain crisis, but many occur without an identifiable trigger. Symptoms from a pain episode generally resolve within a few days to several weeks. Some people with sickle cell disease may experience crises once every few years, while others may have several episodes a year.
    • Anemia is a common complication of the disease because of the shortened life of the sickled red blood cells (RBCs). Those affected may experience fatigue, decreased stamina, dizziness, paleness, shortness of breath, and an increased heart rate. Anemic children may grow and develop more slowly. An aplastic crisis may occur when there is a disruption in RBC production. The most common reason for an acute decrease in RBC production in those affected by sickle cell disease is an infection by parvovirus B19, which selectively affects RBC production in the bone marrow.
    • Increased risk of infections, especially lung infections, can be serious in those with sickle cell disease. According to the Centers for Disease Control and Prevention, pneumonia is a leading cause of death in children with sickle cell disease.
    • Acute chest syndrome, due to vaso-occlusion, is a lung injury that can cause symptoms such as coughing, chest pain, and fever. This condition requires prompt medical attention. It can develop rapidly and become life-threatening.
    • Stroke is one of the most feared complications of sickle cell anemia as it can cause permanent damage and disability. Stroke is more common in children than in adults, occurring in 10% of children with sickle cell anemia.
    • Splenic sequestration is the rapid enlargement of the spleen when many sickle cells become trapped there. Occurring primarily in children, it can cause symptoms such as abdominal pain, nausea, and weakness that can progress to shock. This condition can be life-threatening and may require removal of the spleen.
    • Enlarged liver, with jaundice and yellowing of the whites of the eyes (scleral icterus)
    • Marked enlargement of bone marrow and possible significant deformities of some bones actively involved in producing red blood cells
       

    Other complications of sickle cell disease may include gallstones, bone necrosis (tissue death), leg ulcers, disease of the retina in the eye (retinopathy), caloric and nutritional deficiencies (folic acid, zinc), and sustained erection (priapism). Although present in young patients, people with sickle cell disease who are older than 40 more commonly experience symptoms of kidney disease, with 60% developing proteinuria and a small number developing renal failure.

  • Tests

    The goals of sickle cell tests are to diagnose sickle cell anemia as soon as possible, to identify people with sickle cell trait, and to identify, evaluate, and treat complications as they arise. Newborn screening for sickle cell is now performed routinely throughout the U.S. This testing can identify the specific types of hemoglobin present in a newborn using a few blood drops collected via heel stick.

    Sickle cell tests include:

    • Hemoglobin solubility test and sodium metabisulfite test to screen for sickle cell anemia
    • Hemoglobinopathy (Hb) evaluation through hemoglobin electrophoresis, hemoglobin isoelectric focusing, or HPLC to detect abnormal types and measure relative amounts of hemoglobins present in the red blood cells (RBCs); the test may also be performed after a blood transfusion to ensure that a sufficient amount of normal hemoglobin is present to reduce the risk of damage from RBC sickling.
    • Genetic testing—DNA analysis to investigate mutations in the genes that encode hemoglobin components(beta-globin); DNA testing can also be used to determine if a person is a carrier for sickle cell anemia. This genetic testing (screening) can also be carried out prenatally, either by evaluating cell-free fetal DNA isolated from maternal circulation or by analyzing the DNA of the fetal cells isolated from amniotic fluid via amniocentesis.


    Other tests may include:

    • Complete blood count (CBC) to determine the number and average size of RBCs in the body as well as how much hemoglobin they contain, both of which are often low in those with sickle cell disease
    • Blood smear (also called peripheral smear and manual differential) to screen for abnormal-looking and sickle-shaped RBCs
    • Iron studies to evaluate the body's level of iron, which can be increased in sickle cell patients who have received multiple blood transfusions
    • Bilirubin is used for evaluating individuals with jaundice and suspicion of gallstones, as well as a an additional test for evaluation of hemolytic anemia.
    • Creatinine test to detect increased levels of creatinine in the blood that indicate abnormal kidney function in order to monitor for the development of kidney disease
  • Treatment

    The goals of treatment for sickle cell disease are to relieve pain, minimize complications and organ damage, and prevent infection. Babies and children with sickle cell disease should have all of the regular childhood vaccines, plus influenza vaccine (every year) and pneumococcal vaccine (at 2 and 5 years of age). Newborns with sickle cell disease are often placed on long-term penicillin therapy (begins at 2 months of age and continues until 5 years of age) to prevent pneumonia and other infections.

    During a sickle cell crisis, treatment may involve supportive care, such as drinking lots of fluids and taking over-the counter pain medications, such as ibuprofen or acetaminophen. Sometimes stronger pain medication is required.

    Blood transfusions and pheresis are used to treat severe anemia. Children and adults may be treated with hydroxyurea, a medication that has been found to reduce the number of crises and lessen the severity of those that do occur. The number of crises can also be minimized by avoiding situations that frequently trigger episodes, such as overexertion, dehydration, temperature extremes, changes in altitude, smoking, and stress. Taking folic acid supplements is recommended for people with sickle cell disease because folic acid is necessary for the production of new red blood cells.

    Stroke, aplastic crises, acute chest syndrome, swollen spleens, and occasionally severe crises may need to be treated with blood transfusions or exchange transfusions to raise the red blood cell count and reduce the number of sickle cells. Some people who have had multiple transfusions may require treatment to address iron overload. Those with organ damage and/or organ failure may require additional treatments, such as having their spleen removed.

    According to the National Heart, Lung and Blood Institute, hematopoietic stem cell transplants are the only cure for sickle cell disease. To learn more about this and other treatments, see the NHLBI webpage How Is Sickle Cell Disease Treated?

View Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used. To access online sources, copy and paste the URL into your browser.

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