Sickle cell anemia

Other Names: HbS disease Hemoglobin S Disease SCD Sickle cell disorders Sickling disorder due to hemoglobin S

Sickle cell anemia is a disease in which the body produces abnormally shaped red blood cells that have a crescent or sickle shape. These cells do not last as long as normal, round, red blood cells, which leads to anemia (low number of red blood cells). The sickle cells also get stuck in blood vessels, blocking blood flow.

People who have sickle cell disease have an abnormal protein in their red blood cells. In the United States, most people who have sickle cell disease are of African ancestry, but the condition is also common in people with a Hispanic background. Because the disease runs in families, couples planning to have children can have genetic testing.

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Cause

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Mutations in the HBB gene cause sickle cell disease.

Hemoglobin consists of four protein subunits, typically, two subunits called alpha-globin and two subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene. One particular HBB gene mutation produces an abnormal version of beta-globin known as hemoglobin S (HbS). Other mutations in the HBB gene lead to additional abnormal versions of beta-globin such as hemoglobin C (HbC) and hemoglobin E (HbE). HBB gene mutations can also result in an unusually low level of beta-globin; this abnormality is called beta thalassemia.

In people with sickle cell disease, at least one of the beta-globin subunits in hemoglobin is replaced with hemoglobin S. In sickle cell anemia, which is a common form of sickle cell disease, hemoglobin S replaces both beta-globin subunits in hemoglobin. In other types of sickle cell disease, just one beta-globin subunit in hemoglobin is replaced with hemoglobin S. The other beta-globin subunit is replaced with a different abnormal variant, such as hemoglobin C. For example, people with sickle-hemoglobin C (HbSC) disease have hemoglobin molecules with hemoglobin S and hemoglobin C instead of beta-globin. If mutations that produce hemoglobin S and beta thalassemia occur together, individuals have hemoglobin S-beta thalassemia (HbSBetaThal) disease.

Abnormal versions of beta-globin can distort red blood cells into a sickle shape. The sickle-shaped red blood cells die prematurely, which can lead to anemia. Sometimes the inflexible, sickle-shaped cells get stuck in small blood vessels and can cause serious medical complications.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Types

People who have sickle cell disease have abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in their red blood cells. Hemoglobin is a protein in red blood cells that carries oxygen throughout the body. People who have sickle cell disease inherit two abnormal hemoglobin genes, one from each parent.

The types of sickle cell disease include the following:

• Hemoglobin Sβ0 thalassemia
• Hemoglobin Sβ+ thalassemia
• Hemoglobin SC
• Hemoglobin SD
• Hemoglobin SE
• Hemoglobin SS

In all types of sickle cell disease, at least one of the two abnormal genes causes a person’s body to make hemoglobin S. When a person has two hemoglobin S genes (hemoglobin SS), the disease is called sickle cell anemia. This is the most common and often most severe type of sickle cell disease. Hemoglobin SC disease and hemoglobin Sβ thalassemia are two other common types of sickle cell disease. Hemoglobin SD and hemoglobin SE are much less common.

Risk factors

In the United States, most people who have sickle cell disease are of African ancestry or identify themselves as black.

• About 1 in 13 black or African American babies is born with sickle cell trait.
• About 1 in every 365 black or African American babies is born with sickle cell disease.
• There are also many people who have sickle cell disease who come from Hispanic, southern European, Middle Eastern, or Asian Indian backgrounds.

About 100,000 Americans have sickle cell disease.

Signs and symptoms

Signs and symptoms of sickle cell disease usually begin in early childhood and may include anemia, repeated infections, and periodic episodes of pain (called crises). For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Chronic hemolytic anemia

80%-99% of people have these symptoms

• Recurrent infections(Frequent infections)

30%-79% of people have these symptoms

• Abnormality of the spleen
• Avascular necrosis(Death of bone due to decreased blood supply)
• Chest pain
• Iron deficiency anemia
• Leukocytosis(Elevated white blood count)
• Osteomyelitis(Bone infection)
• Osteoporosis
• Pigment gallstones
• Reticulocytosis(Increased immature red blood cells)
• Thrombocytosis(Increased number of platelets in blood)

5%-29% of people have these symptoms

• Abnormality of the nervous system(Neurologic abnormalities)
• Cholestasis(Slowed or blocked flow of bile from liver)
• Elevated serum [[creatinine)(Elevated creatinine)
• Hypoxemia(Low blood oxygen level)
• Increased lactate dehydrogenase level
• Persistence of hemoglobin F
• Unconjugated hyperbilirubinemia

1%-4% of people have these symptoms

• Increased mean corpuscular volume
• Microcytic anemia

Diagnosis

People who do not know whether they make sickle hemoglobin or another abnormal hemoglobin, such as SC, Sβ thalassemia, and SE, can find out by having their blood tested. This way, they can learn whether they carry a gene—or have the trait—for an abnormal hemoglobin that they could pass on to a child.

With this information, parents can be better informed about the chances of having a child with some type of sickle cell disease, such as hemoglobin SS or SC, Sβ thalassemia, or others. When a child has sickle cell disease, early diagnosis is important to better prevent complications.

Every state in the United States, the District of Columbia, and the U.S. territories require that every baby be tested for sickle cell disease as part of a newborn screening program.

Doctors can also diagnose sickle cell disease before a baby is born. This is done using a sample of amniotic fluid, the liquid in the sac surrounding a growing embryo, or of tissue taken from the placenta, the organ that attaches the umbilical cord to the mother’s womb.

Testing before birth can be done as early as 8 to 10 weeks into the pregnancy. This testing looks for the sickle hemoglobin gene rather than the abnormal hemoglobin.

Abnormal haemoglobin forms can be detected on haemoglobin electrophoresis, a form of gel electrophoresis on which the various types of haemoglobin move at varying speeds. Sickle cell haemoglobin (HgbS) and haemoglobin C with sickling (HgbSC)—the two most common forms—can be identified from there. The diagnosis can be confirmed with high-performance liquid chromatography. Genetic testing is rarely performed, as other investigations are highly specific for HbS and HbC.

In HbS, the complete blood count reveals haemoglobin levels in the range of 6–8 g/dl with a high reticulocyte count (as the bone marrow compensates for the destruction of sickled cells by producing more red blood cells). In other forms of sickle cell disease, Hb levels tend to be higher. A blood film may show features of hyposplenism (target cells and Howell-Jolly bodies).

Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulfite. The presence of sickle haemoglobin can also be demonstrated with the "sickle solubility test". A mixture of haemoglobin S (HbS) in a reducing solution (such as sodium dithionite) gives a turbid appearance, whereas normal Hb gives a clear solution.

Treatment

A blood and bone marrow transplant is currently the only cure for some patients who have sickle cell disease.

Medicines

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Hydroxyurea (Brand name: Droxia)To reduce the frequency of painful crises and to reduce the need for blood transfusions in adult patients with sickle cell anemia with recurrent moderate to severe painful crises (generally at least 3 during the preceding 12 months).
• L-glutamine oral powder (prescription grade) (Brand name: Endari) To reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.
• Hydroxyurea (Brand name: Siklos)To reduce the frequency of painful crises and to reduce the need for blood transfusions in pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crisis.

Penicillin In children who have sickle cell disease, taking penicillin two times a day has been shown to reduce the chance of having a severe infection caused by the pneumococcus bacteria. Newborns need to take liquid penicillin. Older children can take tablets.

Transfusions

Your doctor may recommend transfusion to treat and prevent certain sickle cell disease complications. These transfusions may include: Acute transfusion to treat complications that cause severe anemia. Doctors may also use transfusions when a patient has an acute stroke, in many cases of acute chest crises, and in multi-organ failure. A patient who has sickle cell disease usually receives blood transfusions before surgery, to prevent complications. Red blood cell transfusions to increase the number of red blood cells and provide normal red blood cells that are more flexible than red blood cells with sickle hemoglobin.

Regular or ongoing blood transfusions for people who have had an acute stroke, to reduce the chances of having another stroke. Doctors also recommend blood transfusions for children who have abnormal transcranial Doppler (TCD) ultrasound results, because transfusions can reduce the chance of having a first stroke. Some doctors use this approach to treat complications that do not improve with hydroxyurea.

Blood and bone marrow transplant

Blood and bone marrow transplants are successful in about 85 percent of cases involving children when the donor is related and HLA (human leukocyte antigen)-matched. Even with this high success rate, transplants still have risks. Complications can include severe infections, seizures, and other clinical problems. About 5 percent of people who have received such transplants have died. Sometimes transplanted cells attack the recipient’s organs. This is called graft-versus-host disease. Medicines are given to prevent many of the complications, but they still can happen.

Prognosis

About 90% of people survive to age 20, and close to 50% survive beyond age 50. In 2001, according to one study performed in Jamaica, the estimated mean survival for people was 53 years for men and 58 years for women with homozygous SCD.

NIH genetic and rare disease info

• NIH info on Sickle cell anemia

Sickle cell anemia is a rare disease.

Sickle cell anemia Resources
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