sickle cell anemia

n.
A chronic, usually fatal anemia marked by sickle-shaped red blood cells, occurring almost exclusively in Black people of Africa or of African descent, and characterized by episodic pain in the joints, fever, leg ulcers, and jaundice. The disease occurs in individuals who are homozygous for a mutant hemoglobin gene. Also called sickle cell disease.

For more information on sickle-cell anemia, visit Britannica.com.

Definition

Sickle cell anemia, which is also known as meniscocytosis or sicklemia, is an inherited blood disorder that arises from a gene mutation. As a result, affected hemoglobin molecules have a tendency to stick to one another, forming abnormal strands of hemoglobin within the red blood cells. The cells that contain these strands become stiff and elongated—sickle-shaped.

Because sickle cell anemia is characterized by the rapid loss of red blood cells as they enter the circulation, it is classified as a hemolytic anemia, "hemolytic" referring to the destruction of the cell membrane of red blood cells, resulting in the release of hemoglobin.

Description

Sickle-shaped cells die much more rapidly than normal red blood cells and the body cannot create replacements fast enough. Anemia develops due to the chronic shortage of red blood cells. Further complications arise because sickle cells do not fit well through small blood vessels, and can become trapped. The trapped sickle cells form blockages that prevent oxygenated blood from reaching associated tissues and organs. The damaged tissues and organs cause considerable pain and can lead to serious complications, including stroke and an impaired immune system. Sickle cell anemia primarily affects people with African, Mediterranean, Middle Eastern, and Indian ancestry. In the United States, one in 12 African Americans are carriers. An additional 72,000 Americans have sickle cell anemia, meaning they have inherited the trait from both parents. Among African Americans, approximately one in every 500 babies is diagnosed with sickle cell anemia. Hispanic Americans are also heavily affected; sickle cell anemia occurs in one of every 1,000-1,400 births. Worldwide, it has been estimated that 250,000 children are born each year with sickle cell anemia.

Hemoglobin Structure

Normal hemoglobin is composed of a heme molecule and two pairs of proteins called globins. Humans have the genes to create six different types of globins—alpha, beta, gamma, delta, epsilon, and zeta—but do not use all of them at once. The type of genes expressed depends upon the stage of development: embryonic, fetal, or adult. Virtually all of the hemoglobin produced in humans from ages 2-3 months and onward contains a pair of alpha-globin and beta-globin molecules.

Sickle Cell Hemoglobin

A change, or mutation, in a gene can alter the formation or function of its product. In the case of sickle cell hemoglobin, the gene that carries the blueprint for beta-globin has a tiny alteration that makes it different from the normal gene. This mutation affects a single nucleic acid along the entire DNA strand that makes up the beta-globin gene. (Nucleic acids are the chemicals that make up deoxyribonucleic acid [DNA].) Specifically, the nucleic acid adenine is replaced by a different nucleic acid called thymine.

Because of this seemingly slight mutation, called a point mutation, the finished beta-globin molecule has a single amino acid substitution: valine occupies the spot normally taken by glutamic acid. (Amino acids are the building blocks of all proteins.) This substitution is incorporated into the beta-globin molecule—and eventually returning in a hemoglobin molecule—that does not function normally.

Normal hemoglobin, referred to as hemoglobin A, transports oxygen from the lungs to tissues throughout the body. In the smallest blood vessels, the hemoglobin exchanges the oxygen for carbon dioxide, which it carries back to the lungs for removal from the body. The defective hemoglobin, designated hemoglobin S, can also transport oxygen. However, once the oxygen is released, hemoglobin S molecules have an abnormal tendency to clump together. Aggregated hemoglobin molecules form strands within red blood cells, which then lose their usual shape and flexibility.

The rate at which hemoglobin S aggregation and cell sickling occurs depends on many factors, such as the blood flow rate and the concentration of hemoglobin in the blood cells. If the blood flows at a normal rate, hemoglobin S is reoxygenated in the lungs before it has a chance to aggregate. The concentration of hemoglobin within red blood cells is influenced by an individual's hydration level—that is, the amount of water contained in the cells. If a person becomes dehydrated, hemoglobin becomes more concentrated in the red blood cells. In this situation, hemoglobin S has a greater tendency to clump together and induce sickle cell formation.

Sickle Cell Anemia

Genes are inherited in pairs, one copy from each parent. Therefore, each person has two copies of the gene that makes beta-globin. As long as a person inherits one normal beta-globin gene, the body can produce sufficient quantities of normal beta-globin. A person who inherits a copy of each of the normal and abnormal beta-globin genes is referred to as a carrier of the sickle cell trait. Generally, carriers do not have symptoms, but their red blood cells contain some hemoglobin S.

A child who inherits the sickle cell trait from both parents—a 25% possibility if both parents are carriers—will develop sickle cell anemia. These cells have a decreased life span in comparison to normal red blood cells. Normal red blood cells survive for approximately 120 days in the bloodstream; sickle cells last only 10-12 days. As a result, the bloodstream is chronically short of red blood cells and the affected individual develops anemia.

The sickle cells can create other complications. Due to their shape, they do not fit well through small blood vessels. As an aggravating factor, the outside surfaces of sickle cells may have altered chemical properties that increase the cell's "stickiness." These sticky sickle cells are more likely to adhere to the inside surfaces of small blood vessels as well as to other blood cells. As a result of the sickle cells' shape and stickiness, blockages occasionally form in small blood vessels. Such blockages prevent oxygenated blood from reaching areas where it is needed, causing extreme pain as well as organ and tissue damage.

The severity of the symptoms cannot be predicted based solely on the person's genetic inheritance. Some individuals with sickle cell anemia develop health- or life-threatening problems in infancy but others may have only mild symptoms throughout their lives. For example, genetic factors, such as the continued production of fetal hemoglobin after birth can modify the course of the disease. Fetal hemoglobin contains gamma-globin in place of beta-globin; if enough of it is produced, the potential interactions between hemoglobin S molecules are reduced.

Affected Populations

Worldwide, millions of people carry the sickle cell trait. Individuals whose ancestors lived in sub-Saharan Africa, the Middle East, India, or the Mediterranean region are the most likely to have the trait. The areas of the world associated with the sickle cell trait are also strongly affected by malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. According to a widely accepted theory, the genetic mutation associated with the sickle cell trait occurred thousands of years ago. Coincidentally, this mutation increased the likelihood that carriers would survive malaria outbreaks. Survivors then passed the mutation on to their offspring, and the trait became established throughout areas where malaria was common.

Causes & Symptoms

Symptoms typically appear during the first year or two of life. However, some individuals do not develop symptoms until adulthood and may not be aware that they have the genetic inheritance for sickle cell anemia.

Anemia

Sickle cells have a high turnover rate, and there is an ongoing deficit of red blood cells in the bloodstream. Common symptoms of anemia include fatigue, paleness, and shortness of breath. A particularly severe form of anemia—aplastic anemia—occurs following infection with parvovirus. Though temporary, parvovirus infection causes extensive destruction of the bone marrow, bringing production of new red blood cells to a halt. Bone marrow production resumes after 7–10 days, but given the short lives of sickle cells, even a brief shutdown in red blood cell production can cause a major decline in hemoglobin concentrations. This event is called "aplastic crisis."

Painful Crises

Painful crises, also known as vasoocclusive crises, are a primary symptom of sickle cell anemia in children and adults. The pain may be caused by small blood vessel blockages that prevent oxygen from reaching tissues. An alternate explanation, particularly with regard to bone pain, is that blood is shunted away from the bone marrow but through some mechanism other than blockage by sickle cells.

These crises are unpredictable and can affect any area of the body, although the chest, abdomen, and bones are frequently affected sites. There is some evidence that cold temperatures or infection can trigger a painful crisis, but most crises occur for unknown reasons. The frequency and duration of the pain can vary tremendously. Crises may be separated by more than a year or possibly only by weeks, and they can last from hours to weeks.

The hand-foot syndrome is a particular type of painful crisis, and is often the first sign of sickle cell anemia in an infant. Common symptoms include pain and swelling in the hands and feet, possibly accompanied by a fever. Hand-foot syndrome typically occurs only during the first four years of life, with the greatest incidence at one year.

Enlarged Spleen and Infections

Sickle cells can impede blood flow through the spleen and cause organ damage. In infants and young children, the spleen is usually enlarged. After repeated incidence of blood vessel blockage, the spleen usually atrophies by late childhood. Damage to the spleen can have a negative impact on the immune system, leaving individuals with sickle cell anemia more vulnerable to infections. Infants and young children are particularly prone to life-threatening infections.

Anemia can also impair the immune system, because stem cells—the precursors of all blood cells—are earmarked for red blood cell production rather than white blood cell production. White blood cells form the cornerstone of the immune system within the bloodstream.

Delayed Growth

The energy demands of the bone marrow for red blood cell production compete with the demands of a growing body. Children with sickle cell anemia have delayed growth and reach puberty at a later age than normal. By early adulthood, they catch up on growth and attain normal height, but their weight typically remains below average.

Stroke

Blockage of blood vessels in the brain can have particularly harsh consequences and can be fatal. When areas of the brain are deprived of oxygen, control of the associated functions may be lost. Sometimes this loss is permanent. Common stroke symptoms include weakness or numbness that affects one side of the body, sudden loss of vision, confusion, loss of speech or the ability to understand spoken words, and dizziness. Children between the ages of 1 and 15 have a 30% risk of suffering a stroke. Approximately two-thirds of the children who have a stroke will have at least one more; those who survive typically suffer severe learning disabilities. As of 2003, researchers are investigating various techniques for helping children with memory loss related to strokes caused by sickle cell disease.

Acute Chest Syndrome

Acute chest syndrome can occur at any age, and is caused by sickle cells blocking the small blood vessels of the lungs. This blockage is complicated by accompanying problems such as infection and pooling of blood in the lungs. Affected persons experience fever, cough, chest pain, and shortness of breath. Recurrent attacks can lead to permanent lung damage.

Other Problems

Males with sickle cell anemia may experience a condition called priapism, characterized by a persistent and painful erection of the penis. Due to blood vessel blockage by sickle cells, blood is trapped in the tissue of the penis. Damage to this tissue can result in permanent impotence in adults.

Both genders may experience kidney damage. The environment of the kidney is particularly conducive to sickle cell formation; even otherwise asymptomatic carriers may experience some level of kidney damage. Kidney damage is indicated by blood in the urine, incontinence, and enlarged kidneys.

Jaundice and an enlarged liver are also commonly associated with sickle cell anemia. Jaundice, indicated by a yellow tone in the skin and eyes, may occur if bilirubin levels increase. Bilirubin is the final product of hemoglobin degradation, and is typically removed from the bloodstream by the liver. Bilirubin levels often increase with high levels of red blood cell destruction, but jaundice can also be a sign of a poorly functioning liver.

Some individuals with sickle cell anemia may experience vision problems. The blood vessels that feed into the retina—the tissue at the back of the eyeball—may be blocked by sickle cells. New blood vessels can form around the blockages, but these vessels are typically weak or otherwise defective. Bleeding, scarring, and retinal detachment may eventually lead to blindness.

Diagnosis

Sickle cell anemia is suspected based on an individual's ethnic or racial background, and on the symptoms of anemia. A blood count reveals the presence of anemia, and a sickle cell test reveals the presence of the sickle cell trait.

To confirm a diagnosis of the sickle cell trait or sickle cell anemia, another laboratory test called gel electrophoresis is performed. This test uses an electric field applied across a slab of gel-like material to separate protein molecules based on their size, shape, or electrical charge. Although hemoglobin S (sickle) and hemoglobin A (normal) differ by only one amino acid, they can be clearly separated using gel electrophoresis. If both types of hemoglobin are identified, the individual is a carrier of the sickle cell trait; if only hemoglobin S is present, the person most likely has sickle cell anemia.

The gel electrophoresis test is also used as a screening method for identifying the sickle cell trait in newborns. More than 40 states screen newborns in order to identify carriers and individuals who have inherited the trait from both parents.

Treatment

In general, treatment of sickle cell anemia relies on conventional medicine. However, alternative therapies may be useful in pain control.

Massage

The daily pain caused by sickle cell disease has been shown to be managed by massage. A pilot study whose results were published in 1999 indicated that those who received massage reported less perception of pain than those who were part of a relaxation control group during the research. Massage is recommended as a complementary treatment in the management of the chronic disease.

Pain Diaries

A 2001 study revealed that diaries kept by children and adolescents could help the patients and their families better manage sickle cell pain from home. If children (who are old enough to read and write) can record pain episodes, they have better recall and provide improved documentation for physicians and parents so they can relate pain episodes to possible causes.

Acupuncture

Acupuncture may relieve some of the pain caused by sickle cell disease. For longer-lasting results, acupuncturists indicate that the treatment works with the body's subtle energies by manipulating the "chi" to remove blockages and allow the body to heal itself. Acupuncture uses extremely thin needles that are inserted into various areas of the body, with placement depending on the patient's condition. Each treatment usually takes 20-45 minutes.

Diet

While the pain of sickle cell disease ranges from acute to chronic, simple alterations to the diet are one way to help those who endure the illness. Foods like horseradish, cassava, yams, corn, bamboo shoots, sweet potatoes, and lima beans contain cyanogenic glucosides, or natural plant compounds that are recommended additions to the diet. These natural plant compounds interact with bacteria in the large intestine and aid the body in producing a type of hemoglobin that can effectively carry oxygen through blood cells—possibly leading to less pain.

Allopathic Treatment

Early identification of sickle cell anemia can prevent many problems. The highest death rates occur during the first year of life due to infection, aplastic anemia, and acute chest syndrome. If anticipated, steps can be taken to avert these crises. With regard to long-term treatment, prevention of complications remains a main goal. Sickle cell anemia cannot be cured—other than through a risky bone marrow transplant—but treatments are available for symptoms.

Pain Management

Pain is one of the primary symptoms of sickle cell anemia, and controlling it is an important concern. The methods necessary for pain control are based on individual factors. Some people can gain adequate pain control through over-the-counter oral painkillers (analgesics), local application of heat, and rest. Others need stronger methods, which can include administration of narcotics.

Blood Transfusions

Blood transfusions are usually not given on a regular basis but are used to treat painful crises, severe anemia, and other emergencies. In some cases, such as treating spleen enlargement or preventing stroke from recurring, blood transfusions are given as a preventative measure. Regular blood transfusions have the potential to decrease formation of hemoglobin S and reduce associated symptoms.

Drugs

Infants are typically started on a course of penicillin that extends from infancy to age six. This treatment is meant to ward off potentially fatal infections. Infections at any age are treated aggressively with antibiotics. Vaccines for common infections, such as pneumococcal pneumonia, are administered when possible.

Emphasis is being placed on developing drugs that treat sickle cell anemia directly. The most promising of these drugs in the late 1990s is hydroxyurea, a drug that was originally designed for anticancer treatment. Hydroxyurea has been shown to reduce the frequency of painful crises and acute chest syndrome in adults, and to lessen the need for blood transfusions. Hydroxyurea seems to work by inducing a higher production of fetal hemoglobin. The major side effects of the drug include decreased production of platelets, red blood cells, and certain white blood cells. The effects of long-term hydroxyurea treatment are unknown; however, a nine-year follow-up study of 299 adults with frequent painful crises reported in 2003 that taking hydroxyurea was associated with a 40% reduction in mortality.

Bone Marrow Transplantation

Bone marrow transplantation has been shown to cure sickle cell anemia in severely affected children. Indications for a bone marrow transplant are stroke, recurrent acute chest syndrome, and chronic unrelieved pain. Bone marrow transplants tend to be the most successful in children; adults have a higher rate of transplant rejection and other complications.

Gene Research

Replacing the gene that produces the defective hemoglobin in sickle cell disease patients with one that makes normal hemoglobin may be a possible treatment due to recent research. According to a 1998 report in Science, researchers studied the blood cells from people who carry the sickle cell gene. By using an enzyme called a ribosome, the study was able to alter sickle cells into normal cells. The ribosome cut out the mutated instructions in the cells' genetic pattern and replaced them with the correct instructions. Researchers hope that this gene therapy will allow the cells to make normal hemoglobin—leading to the ultimate treatment for those with sickle cell disease.

In late 2001 genetic scientists reported that they had designed a gene that might lead to a future treatment of sickle cell anemia. Although the gene had not tested in humans, early results showed that the injected gene protected cells from sickling. As of 2003, experiments in gene therapy for sickle cell disease have been carried out in mice, using lentiviral vectors to transfer the corrective gene into the mouse's stem cells. This technique, however, has not yet been attempted in human subjects as of late 2003.

Expected Results

Several factors aside from genetic inheritance determine the prognosis for affected individuals. Therefore, predicting the course of the disorder based solely on genes is not possible. In general, given proper medical care, persons with sickle cell anemia are in fairly good health most of the time. The life expectancy for these individuals has steadily increased over the last 30 years, and many are now surviving past the age of 50. In the United States, the average life expectancy for men with sickle cell anemia is 42 years; for women, it is 48 years. The most common causes of death are infections, lung disease, the blocking of a blood vessel supplying a vital organ, and kidney failure. Pregnant women with sickle cell disease are particularly vulnerable to infection, most often pneumonia or urinary tract infections.

Prevention

The sickle cell trait is a genetically linked, inherited condition. Inheritance cannot be prevented but may be predicted. Screening is recommended for individuals in high-risk populations; in the United States, African Americans, and Hispanic Americans have the highest risk of being carriers.

Screening at birth offers the opportunity for early intervention; more than 40 states include sickle cell screening as part of the usual battery of blood tests done for newborns. Pregnant women and couples planning to have children may also wish to be screened to determine their carrier status. Carriers have a 50% chance of passing the trait to their offspring. Children born to two carriers have a 25% chance of inheriting the trait from both parents and having sickle cell anemia. Carriers may consider genetic counseling to assess any risks to their offspring. The sickle cell trait can also be identified through prenatal testing, specifically through use of amniotic fluid testing or chorionic villus sampling.

By maintaining a good diet, staying well hydrated with plenty of fluids, exercising regularly, and getting enough sleep those with sickle cell disease may help their bodies remain strong and ward off fatigue and dehydration.

Resources

Books

"Anemias Caused by Excessive Hemolysis: Sickle Cell Diseases." Section 11, Chapter 127 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Beutler, Ernest. The Sickle Cell Diseases and Related Disorders. Williams Hematology, edited by Ernest Beutler, et al. 5th ed. New York: McGraw-Hill, 1995.

Bloom, Miriam. Understanding Sickle Cell Disease. Jackson, MS: University Press of Mississippi, 1995.

The Editors of Time-Life Books. Sickle Cell Anemia. The Medical Advisor: The Complete Guide to Alternative & Conventional Treatments, Richmond, VA: Time-Life Inc., 1996.

Embury, Stephen H., et al., eds. Sickle Cell Disease: Basic Principles and Clinical Practice. New York: Raven Press, 1994.

"Pregnancy Complicated by Disease: Hemoglobinopathies." Section 18, Chapter 251 in The Merck Manual of Diagnosisand Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 2002.

Periodicals

Davies, S. C., and A. Gilmore. "The Role of Hydroxyurea in the Management of Sickle Cell Disease." Blood Reviews 17 (June 2003): 99–109.

Egbert Maikler, Virginia, et al." Children's and Adolescents' Use of Diaries for Sickle Cell Pain." Journal of the Society of Pediatric Nurses 6. no. 4 (October – December 2001): 161 – 169.

Harris, Leslie. "Living Well with Sickle Cell." Essence (September 1999): 58.

Nienhuis, A. W., H. Hanawa, N. Sawai, et al. "Development of Gene Therapy for Hemoglobin Disorders." Annals of the New York Academy of Science 996 (May 2003): 101–111.

Seppa, N. "Gene Therapy for Sickle-cell Disease?." Science News 160, no. 24 (December 15, 2001): 372.

"Sickle Cell Pain Relieved by Massage." Massage Magazine (June 30, 1999): 52.

Steinberg, M. H., F. Barton, O. Castro, et al. "Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits up to 9 Years of Treatment." Journal of the American Medical Association 289 (April 2, 2003): 1645–1651.

Winrow, N., and E. R. Melhem. "Sickle Cell Disease and Stroke in a Pediatric Population. Evidence-Based Diagnostic Evaluation." Neuroimaging Clinics of North America 13 (May 2003): 185–196.

Yerys, B. E., D. A. White, C. F. Salorio, et al. "Memory Strategy Training in Children with Cerebral Infarcts Related to Sickle Cell Disease." Journal of Pediatric Hematology and Oncology 25 (June 2003): 495–498.

Organizations

Mayo Foundation for Medical Education and Research. .

Sickle Cell Disease Association of America. 200 Corporate Point, Suite 495, Culver City, CA 90230-7633. (310) 216-6363. (800) 421-8453. .

Sickle Cell Disease Program, Division of Blood Diseases and Resources. National Heart, Lung, and Blood Institute. II Rockledge Centre, 6701 Rockledge Dr. MSC 7950, Bethesda, MD 20892-7950. (301) 435-0055.

[Article by: Beth Kapes; Teresa Norris; Rebecca J. Frey, PhD]

Definition

Sickle cell anemia, also called sickle cell disease (SS disease), is an inherited condition caused by having abnormal hemoglobin, the protein that carries oxygen in the blood. People with sickle cell anaemia have sickle hemoglobin (HbS) which is different from the normal hemoglobin (HbA).

Description

Children with sickle cell anemia produce two abnormal hemoglobin proteins (inheriting one from each parent), which makes their red blood cells easily destructible while giving them a sickle-like shape. Since the red blood cells do not have a normal shape, their circulation in the small blood vessels is impaired as well as the function of the abnormal hemoglobin (HbS) which can no longer carry oxygen with maximum efficiency.

Transmission

Sickle cell anemia is usually inherited from parents who are carriers, who have the sickle cell trait—a milder form of sickle cell anemia, or one abnormal hemoglobin.

Demographics

Sickle cell anemia and sickle cell trait are found mainly in people whose families come from Africa, the Caribbean, the Eastern Mediterranean, Middle East, and Asia. In the United States, sickle cell anemia affects some 72,000 people. The families of most of the people affected come from Africa. The disease occurs in about one in every 600 African-American births and in one in every 1,000 to 1,400 Hispanic-American births. Some 2 million Americans carry the sickle cell trait and about one in 12 African Americans have the trait.

Causes and Symptoms

Sickle cell anemia is caused by an error in the gene that signals the body how to make hemoglobin. The defective gene tells the body to make the abnormal hemoglobin HbS instead of the normal HbA, and this results in deformed red blood cells. The error in the hemoglobin gene is due to a genetic mutation that occurred many thousands of years ago in people living in Africa, the Mediterranean basin, the Middle East, and India. A deadly form of malaria was very common at that time, and research has shown that in areas where malaria was endemic, children who inherited one HbS gene and who, therefore, carried the sickle cell trait, had a survival advantage because, unlike the children who had normal HbA genes, they survived malaria. They grew up, had their own children, and passed on the gene for HbS.

Symptoms or complications associated with sickle cell anemia usually start after the age of four to six months and can include all or some of the following:

• anemia, caused by low amounts of red blood cells in the bloodstream, resulting in insufficient oxygen delivery to tissues and organs
• vaso-occlusive pain, meaning severe episodes of pain in the arms, legs, or back, due to impaired blood circulation in the blood vessels
• chest pain and fever with coughing
• dactylitis, or hand-foot syndrome, with painful swelling of the bones in the hands or feet of young children
• aplastic crises, during which the body stops making new red blood cells causing severe anemia usually following an infection with the parovirus B19, which causes fifth disease
• priapism, a painful and prolonged erection
• stroke, usually causing sudden weakness of one side of the body
• acute splenic sequestration, with pooling of blood causing a sudden enlargement of the spleen
• jaundice, a yellowing of the skin and white of the eyes
• frequent infection with certain bacteria, particularly pneumococcus and salmonella, which are due to auto-infarction of the spleen or death of the spleen due to poor blood flow

When to Call the Doctor

Children suffering from sickle anemia have episodes during which they suddenly become unwell or complain of severe abdominal or chest pain, headache, stiffness of the neck or drowsiness. Parents should know that a child having a sickle cell crisis requires urgent hospital treatment. They should also call a doctor if the child has a temperature above 101°F (38.5°C).

Diagnosis

The diagnosis of sickle cell anemia is established during the newborn screen testing that is performed in the nursery at time of birth. For children who are not tested, an electrophoresis test of the blood can detect the abnormal hemoglobin of sickle cell anemia. This test measures the speed at which a molecule moves in a gel and can detect abnormal hemoglobin HbS.

Treatment

Treatment usually includes frequent monitoring of red blood counts, antibiotics for infections, transfusions for aplastic crises and splenic sequestration when required, and oxygen as well as respiratory support for chest syndrome. Some patients with severe symptoms receive regular blood transfusions to prevent crises and/or other complications such as stroke and organ damage.

Children with sickle cell disorders are at risk of developing severe infections, and penicillin is usually prescribed to prevent dangerous pneumococcal infections.

Sickle cell pain can be managed with a variety of measures including the following:

• warmth, to increase the blood flow, by massaging and rubbing and by heat from hot water bottles and deep heat creams
• bandaging to support the painful region
• rest
• getting the child to relax, by deep breathing exercises and distracting the attention, and by other psychological methods
• use of pain-killing medicines (analgesics)

Analgesics should only be given as recommended by the treating physician. The gentlest analgesic usually prescribed is paracetamol, given three times a day (62.5 mgm under 12 months; 125 mgm 1–4 years; 250 mgm 4–10 years; 500 mgm 10–14 years; and 1 gm 15 years upwards). The next gentlest is codeine phosphate, given four times a day, at 1–2 mgm for every kilogram of body weight.

Bone marrow transplantation has been shown to provide a cure for severely affected children with sickle cell disease, but the procedure is not entirely without risk. In addition, the marrow must come from a healthy matched sibling donor and only about 18 percent of children with sickle cell anemia are likely to have a matched sibling.

Alternative Treatment

Research contributed a great deal about sickle cell anemia from 1970 to the early 2000s concerning what causes it, how it affects the patient, and how to treat it. Scientists were as of 2004 starting to be successful at developing drugs that prevent the symptoms of sickle cell anemia and procedures that they hope should eventually provide a cure. Drug research is focused on identifying drugs, such as hydroxyurea, that can increase the level of fetal hemoglobin in the blood. Fetal hemoglobin is a form of hemoglobin that all humans produce before birth, but most stop producing it after birth. It has been observed that some children with sickle cell anemia continue to produce large amounts of fetal hemoglobin after birth, and studies have shown that these children have less severe cases of the disease. Fetal hemoglobin seems to prevent "sickling" of red cells, and cells containing fetal hemoglobin tend to survive longer in the bloodstream. Butyrate, a substance widely used as a food additive, was also being investigated as of 2004 as an agent that may increase fetal hemoglobin production.

Nutritional Concerns

Thirst and dehydration caused by not drinking enough, even if thirst is not felt, are known to trigger sickle pain. Parents should accordingly monitor fluid intake closely.

Children with sickle cell anemia are anemic to various degrees. Most of the time they feel quite well, but if the anemia gets worse, they may feel very tired. Folic acid, a vitamin found in fruit and vegetables, supports making blood and anemic children especially need it to prevent them from becoming run down.

Prognosis

Sickle cell anemia is an inherited disease and lasts a lifetime.

Prevention

Both sickle cell trait and sickle cell anemia are inherited. Therefore, parents can pass it to their offspring. It is important for parents to get tested. If one partner has sickle cell trait and the other does not, their children each have a 50 percent chance of having the sickle cell trait, and a 50 percent chance of having normal hemoglobin. If one parent has sickle cell trait it is extremely important that the other parent be tested. If both parents have sickle cell trait, there is a 25 percent chance that the child will have normal hemoglobin, a 50 percent chance that the child will have the sickle cell trait, and a 25 percent chance the child will have sickle cell disease. If both parents have sickle cell trait and want to know whether the unborn child has sickle cell anemia, testing can be performed as early as the tenth week of pregnancy. If the results are normal, the parents can be reassured. If the tests show that the baby will be affected, the parents can be better prepared and they can make an informed decision concerning the pregnancy.

Parental Concerns

Parents should be aware that children with sickle cell anemia are also at increased risk of infection, especially from the Streptococcus pneumonia and H. influenzae bacteria.

Sickle cell anemia does not affect intelligence. Children with sickle cell disorders can almost always attend school and participate fully in normal activities. The child's teacher and the school principal should know of the diagnosis and understand the limitations sickle cell anemia can impose on a child, for instance the need for frequent drinks and easy access to the bathroom, and the triggering of pain by over-exertion or cold.

See also Anemias.

Resources

Books

Gillie, Oliver. Sickle Cell Disease (Just the Facts). Chicago: Heineman Library, 2004.

Gordon, Melanie A. Let's Talk about Sickle Cell Anemia. New York: Powerkids Press, 2000.

Platt, Alan F., and A. Sacerdote. Hope and Destiny: A Patient's and Parent's Guide to Sickle Cell Disease and Sickle Cell Trait. Roscoe, IL: Hilton Publishing Co., 2003.

Periodicals

Fullerton, H. J., et al. "Declining stroke rates in Californian children with sickle cell disease." Blood 104, no. 2 (July 2004): 336–39.

Quinn, C. T., et al. "Survival of children with sickle cell disease." Blood 103, no. 11 (June 2004): 423–27.

Steinberg, M. H. "Therapies to increase fetal hemoglobin in sickle cell disease." Current Hematology Reports 2, no. 2 (March 2003): 95–101.

Zimmerman, S. A., et al. "Sustained long-term hematologic efficacy of hydroxyurea at maximum tolerated dose in children with sickle cell disease." Blood 103, no. 6 (March 2004): 239–45.

Organizations

American Sickle Cell Anemia Association (ASCAA). 10300Carnegie Avenue, Cleveland Clinic EEb18, Cleveland, OH 44106. Web site: www.ascaa.org.

Sickle Cell Society. 54 Station Road, London, NW10 4UA, UK. Web site: www.sicklecellsociety.org.

Web Sites

"Sickle Cell Anemia." Medline Plus. Available online at www.nlm.nih.gov/medlineplus/sicklecellanemia.html (accessed November 14, 2004).

[Article by: Monique Laberge, Ph.D.]

---

A hereditary form of anemia in which the red blood cells become sickle-shaped (shaped like a crescent) and less able to carry oxygen.

Sickle cell anemia is a chronic disease and occurs most frequently in people of African descent.

Occurrence of drepanocytes (sickle cells) in the blood.