Sickle Cell Anemia

Sickle cell anemia, also called sickle cell disease, is a hereditary disorder in which abnormal hemoglobin * within the red blood cells (RBCs) causes the cells to take on abnormal sickle (crescent) shapes. This shape decreases the ability of the hemoglobin to transport oxygen throughout the body. The sickled cells tend to bunch up and clog the blood vessels, and they tend to break apart more easily than normal RBCs. Clogging of the blood vessels may cause inflammation * , pain, tissue damage, and anemia * .




Sickle red blood cells (left) and normal red blood cells (right).





Sickle red blood cells (left) and normal red blood cells (right).

What Are the Sickle Cell Trait and Sickle Cell Disease?

Normally, red blood cells (RBCs) are round and flat, like a saucer. They pass easily through the tiniest blood vessels. Red blood cells sickle, or take on the crescent shape, when they carry an abnormal form of hemoglobin called hemoglobin S. The abnormality in hemoglobin S occurs due to the presence of a faulty gene * .

People inherit one set of genes from each parent. They can inherit either two normal hemoglobin genes (HbA), one normal hemoglobin gene and one gene for the abnormal hemoglobin gene (HbS), or two abnormal HbS genes, depending on the composition of their parents’ genes.

When a person carries one HbS and one HbA gene, the presence of the normal gene is sufficient to override the effects of the HbS gene, so the symptoms of sickle cell disease do not develop. These people, however, are said to have the sickle cell trait or to be carriers of the sickle cell trait, and they may pass it on to their children. Prospective parents who are likely to carry the HbS gene may wish to be tested for its presence and receive genetic counseling before having children.

When people inherit two abnormal HbS genes, one from each parent, they have sickle cell disease, and they show symptoms of that disease. They have only abnormal HbS genes to pass on to their children.

Sickle cell disease is a genetic *

Among people of African ancestry in the United States, about eight in every 100 individuals carry at least one HbS gene (which means they have the sickle cell trait) and about 40,000 people carry two copies of the HbS gene (which means they have sickle cell disease).




The inheritance pattern for the sickle cell gene HbS.





The inheritance pattern for the sickle cell gene HbS.
Illustration by Frank Forney. © 2016 Cengage Learning®.

What Are the Effects of Sickle Cell Disease?

People who have sickle cell disease get infections more frequently than other people. In 1987 the National Institutes of Health recommended that all babies, regardless of ethnic or racial background, be tested at birth for the presence of HbS. Babies with sickle cell disease are often given antibiotics * to prevent infections. Before this screening became common, many babies born with sickle cell disease died in infancy. Later, the use of preventive antibiotics significantly reduced the number of babies who died.

Infants, older children, and adults with sickle cell disease periodically experience bouts of critical illness called crises. They also suffer from complications of anemia.

Because sickle cell disease is hereditary, people are born with it and will have it all their lives. No one can catch sickle cell disease or sickle cell trait from another person, and there is no cure for the disease as of 2016.

Crises
AT THE FOREFRONT OF MEDICAL SCIENCE

In 1949 Linus Pauling (1901–1994) and associates published an article in Science magazine (“Sickle Cell Anemia, a Molecular Disease”). This paper explains how protein electrophoresis was used to show how sickle cell hemoglobin differed in structure from normal hemoglobin. Hemoglobin S (sickle cell) differs from normal adult hemoglobin (called hemoglobin A) by only a single amino acid substitution (a valine replacing a glutamine in the sixth position of the beta chain of globin).

This breakthrough concept marked the birth of molecular biology as a field of study. Medical science entered the era of molecular biology, a time in which the focus is on understanding health and disease in terms of the structure of molecules.

In the 1970s there was growing understanding that sickle trait conveys a survival advantage to people in malarial areas, which represented a breakthrough concept in the field of human genetics. It explained the clustering and concentration of hemoglobin S genes in certain areas of the world and constituted an example of human evolution in action.

In the 21st century, with the development of genetic engineering, it became possible to remove the gene for sickle hemoglobin from the genome of families with sickle cell anemia so that their children will not carry the disease.

Crises may be brought on by respiratory infection, by a loss of body fluids from vomiting or diarrhea, by situations in which the body's need for oxygen is increased, or they may occur for no obvious reason. They may last for several days and cause fever and sharp, intense pain in the back, abdomen, chest, arms, and legs. In infants, the hands and feet may become swollen and painful.

Crises may damage nearly any part of the body, but especially the bones, kidneys, intestines, lungs, liver, spleen, and the central nervous system * , including the brain. There may also be eye damage, stroke * , convulsions * , or paralysis * . The damage is caused because the clumping of RBCs in a blood vessel deprives tissues of oxygen.

Many people with sickle cell disease go for long periods during which they may feel relatively well and engage in most normal activities and are free of crises (in remission). Others may experience pain on a daily basis, and some need to be hospitalized as a result of crises several times per year.

Anemia

The anemia may become so severe that a person will need to have a blood transfusion * . The long-term effect of anemia is that the heart has to work harder to pump more blood through the body. Over time the heart enlarges, increasing the risk of heart attack and heart failure.

Other complications of sickle cell disease

People who have sickle cell disease are more susceptible to all kinds of bacterial and fungal infections. They are more likely to have strokes and to experience kidney failure. In some people, the liver enlarges, and by age 30, 70 percent of people with sickle cell disease have developed gallstones * .

Modern medicine has increased the survival of people with sickle cell disease. About half the people with sickle cell disease live beyond 50 years of age. Still, living with the pain and complications of this condition can cause emotional stress on both the person with the disease and the family.

How Do Doctors Diagnose Sickle Cell Disease?

Sickle cell disease and sickle cell trait can be diagnosed by a blood test, which detects the presence of HbS and other abnormal hemoglobins. A complete blood count (CBC) counts the number of RBCs and checks for abnormal shapes.

How Do Doctors Treat Sickle Cell Disease?

There is no cure for sickle cell anemia. Most treatment is preventive and directed toward symptoms. Antibiotics may be given to prevent infections. Fluid intake is important to prevent dehydration * , a major cause of sickling. Folic acid may be given daily to lessen the anemia by helping to make new red cells. Children are given a complete set of immunizations. Lifestyle habits that can help sickle cell patients stay healthy and have fewer crises include drinking plenty of water, avoiding extremes of heat and cold, avoiding stress and overexertion, getting enough sleep, and having regular medical checkups.

A Possible Benefit of the Sickle Cell Trait

Sickle cell disease is especially prevalent among people of African or African American descent. No one knows for sure why this is so. However, it is believed that the gene that causes sickle cell disease also provides natural resistance to malaria, a disease that is often fatal. The parts of Africa where malaria is most prevalent, such as Ghana and Nigeria, are also the areas where the incidence of sickle cell anemia and sickle cell trait is greatest. It is believed that the gene that causes the sickle cell trait gives these people some advantage in surviving malaria, which allows them to live and reproduce, thereby passing the gene along to later generations. However, people with sickle cell disease (two copies of the HbS sickle cell gene) do not have this advantage and are more likely to die of malaria.

Treatment in a sickle cell crisis may require oxygen therapy, painrelieving medications, antibiotics, and intravenous fluids to offset dehydration. Blood transfusions may also have to be performed. Treatment of pain is a major concern. The benefits of different pain relievers and their unwanted side effects must be balanced for each patient.

Research is ongoing to find better ways to treat people with sickle cell disease. Some of these research efforts are directed at stimulating the production of fetal hemoglobin, a form of hemoglobin found in infants, even those with sickle cell disease. Other research is directed toward the development of drugs that block dehydration in cells. Gene therapy and the transplantation of healthy bone marrow * that makes normal red blood cells are also under investigation.

See also Anemia, Bleeding, and Clotting • Genetic Diseases: Overview • Heart Disease: Overview • Pain • Stroke

Resources

Books and Articles

Eveleth, Rose. “Exercising Caution: Intensive Athletic Activity Could Be Fatal to Those with Sickle Cell Trait.” Scientific American, August 13, 2013. Available at: http://www.scientificamerican.com/article/athletic-activity-could-be-fatal-to-those-with-sickle-cell-trait/ (accessed July 10, 2016).

Hambleton, Laura. “Sickle Cell Disease Once Meant a Short and Painful Life, but Now There's Growing Hope.” Washington Post, March 3, 2014. http://www.washingtonpost.com/national/health-science/sickle-cell-disease-once-meant-a-short-and-painful-life-but-now-theres-growing-hope/2014/03/03/d964d318-6275-11e3-91b3f2bb96304e34_story.html (accessed July 10, 2016).

Websites

Centers for Disease Control and Prevention. “Sickle Cell Disease (CSD).” http://www.cdc.gov/ncbddd/sicklecell/index.html (accessed July 10, 2016).

MedlinePlus. “Sickle Cell Anemia.” U.S. National Library of Medicine. https://www.nlm.nih.gov/medlineplus/sicklecellanemia.html (accessed July 10, 2016).

Organizations

National Heart, Lung, and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. Telephone: 301-592-8573. Website: http://www.nhlbi.nih.gov (accessed July 10, 2016).

Sickle Cell Disease Association of America. 3700 Koppers St., Suite 570, Baltimore, MD 21227. Toll-free: 800-421-8453. Website: http://www.sicklecelldisease.org (accessed July 10, 2016).

Sickle Cell Information Center. Grady Memorial Hospital, PO Box 109, 80 Jesse Hill Jr. Dr. SE, Atlanta, GA 30303. Telephone: 404-616-3572. Website: http://www.scinfo.org (accessed July 10, 2016).

* hemoglobin (HE-muh-glo-bin) is the oxygen-carrying pigment of the red blood cells.

* inflammation (in-fla-MAY-shun) is the body's reaction to irritation, infection, or injury that involves swelling, pain, redness, and warmth.

* anemia (uh-NEE-me-uh) is a blood condition in which there is decreased hemoglobin in the blood and usually lower than normal numbers of red blood cells.

* genes (JEENS) are chemical structures composed of deoxyribonucleic acid (DNA) that determine a person's body structure and physical characteristics. Inherited from a person's parents, genes are contained in the chromosomes found in the body's cells.

* genetic (juh-NEH-tik) refers to heredity and the ways in which genes control the development and maintenance of organisms.

* antibiotics (an-tie-by-AH-tiks) are drugs that kill or slow the growth of bacteria.

* central nervous system (SEN-trul NER-vus SIS-tem) is the part of the nervous system that includes the brain and spinal cord.

* stroke is an event that occurs when a blood vessel bringing oxygen and nutrients to the brain bursts or becomes clogged by a blood clot or other particle. As a result, nerve cells in the affected area of the brain cannot function properly.

* convulsions (kon-VUL-shuns), also called seizures, are involuntary muscle contractions caused by electrical discharges within the brain and are usually accompanied by changes in consciousness.

* paralysis (pah-RAHL-uh-sis) the loss or impairment of the ability to move some part of the body.

* blood transfusion is the process of giving blood (or certain cells or chemicals found in the blood) to a person who needs it due to illness or blood loss.

* gallstones (GAWL-stonz) hard masses that form in the gallbladder or bile duct

* dehydration (dee-hi-DRAYshun) is a condition in which the body is depleted of water, usually caused by excessive and unreplaced loss of body fluids through sweating, vomiting, or diarrhea.

* bone marrow is the soft tissue inside bones where blood cells are made.

  This information is not a tool for self-diagnosis or a substitute for professional care.