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Sickle Cell Disease

Synonyms of Sickle Cell Disease

  • Sickle Cell Anemia
  • Sickle Cell Trait

Disorder Subdivisions

  • Sickle Cell-Hemoglobin C Disease
  • Sickle Cell-Hemoglobin D Disease
  • Sickle Cell-Thalassemia Disease

General Discussion

Sickle cell disease is a rare inherited blood disorder. It is characterized by the presence of sickle or crescent shaped red blood cells (erythrocytes) in the bloodstream. These abnormally-shaped cells become rigid and lodge themselves in the very tiny blood vessels (capillaries) of the peripheral blood system (blood vessels outside of the heart). The capillaries become clogged, preventing the normal flow of oxygen to tissues. Common symptoms associated with sickle cell disease include chest pain, frequent infections, yellowing of the skin (jaundice), and low levels of circulating red blood cells (anemia). Sickle cell disease has several recognized forms including sickle cell anemia, sickle cell hemoglobin C disease and sickle cell thalassemia disease. Sickle cell disease is inherited as an autosomal recessive trait.

Symptoms

Symptoms of sickle cell disease develop due to the low level of healthy hemoglobin in the red blood cells (erythrocytes) and a resulting inability of the blood to supply oxygen to the tissues of the body. Sickle cell disease is characterized by sudden acute attacks of pain particularly in the chest, painful inflammation of the fingers or toes (sickle cell dactylitis), swollen hands or feet, a lingering upper respiratory infection and/or a pale color of the tongue and lips. Additional symptoms may include irritability; crying; poor eating habits; an enlarged spleen (splenomegaly); an enlarged liver (hepatomegaly); yellow discoloration of the skin (jaundice); stroke; a yellow appearance of the eyeballs (scleral icterus); and/or heart murmurs.

The symptoms of sickle cell disease vary greatly from case to case. Some affected individuals will have very mild symptoms; others may have a severe form of the disorder. The symptoms typically begin in the first three years of life. In children aged three to five, the signs of the disease are often pain in the chest, abdomen, limbs and joints. Joint pain generally follows exposure to cold, overexertion, infection and/or dehydration. Joint pain is usually not accompanied by joint swelling. Children with sickle cell disease may grow slowly and have many nosebleeds. Affected children are more susceptible to a variety of infections.

In adolescents and young adults the symptoms of sickle cell disease may include severe joint pain, delayed puberty, progressive anemia, leg sores, nosebleeds and/or dental disease. Kidney disease and a scarring of retinal tissues of the eyes may also occur. Occasionally sickle cell disease may cause a loss of bone, particularly the top of the thigh bone (osteonecrosis of the femoral head). The loss of bone may cause pain in the joints when walking, standing and/or lifting. Cardiac symptoms may also occur in people with sickle cell disease including a rapid heartbeat (tachycardia), heart murmurs, a higher risk than the general population of developing a stroke, and/or other heart problems.

Sickle cell disease may also appear in people over 20 years of age. When sickle cell disease occurs in adulthood people generally experience pain in the chest, abdomen, limbs and/or joints. These painful episodes may become less frequent with advancing age. Leg sores, inflammation of the retina (retinitis) of the eyes, and gallbladder disease are often present. Men with sickle cell disease may experience painful, prolonged erections (priapism).

Impaired blood flow associated with sickle cell disease can potentially cause damage to most organ systems of the body including the kidneys, livers, spleen, and eyes.

Both sickle cell-thalassemia disease and sickle cell-hemoglobin C disease are milder forms of sickle cell disease. The symptoms of hemoglobin C disease occur later in life than those of sickle cell disease.

Causes

Sickle cell disease is a rare blood disorder that is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

People who inherit only one sickle cell gene are said to have "sickle cell trait" and are generally symptom free carriers who can pass the gene on to their offspring. However, people with sickle cell disease must inherit two genes for sickle cell (one from each parent) in order to have the disease.

Affected Populations

Sickle cell disease affects 0.6 percent of the African American population in the United States (approximately 90,000 cases in the United States). Sickle cell disease affects approximately one in every 350 African American newborns. The sickle cell trait is present in approximately 40 percent of the general population in some areas of Africa. The incidence of sickle cell trait in Americans of African descent is 9 percent. Americans whose ancestry is Asiatic Indian, Italian, Greek or Mediterranean may also be affected by sickle cell disease.

Related Disorders

Symptoms of the following disorders can be similar to those of sickle cell disease. Comparisons may be useful for a differential diagnosis:

Hereditary spherocytic hemolytic anemia is a rare inherited disorder of the blood that causes the red blood cells to become sphere-shaped making it difficult for them to circulate through the spleen. This causes excessive red blood cell destruction. The symptoms of hereditary spherocytic hemolytic anemia may be present at birth or not be apparent for years. In many people the symptoms are so mild that the disease is not recognized. Symptoms may include fatigue and a yellow or jaundice appearance to the skin. Generally the spleen is enlarged resulting in abdominal discomfort. An infection is the most common trigger of an anemic crisis (dangerously low levels of red blood cells in the blood). Trauma or pregnancy may worsen the anemic crisis. The child may experience fever, headache, loss of appetite, vomiting, leg sores, and general weakness. Some children experience nosebleeds. (For more information on this disorder, choose "Hereditary Spherocytic Hemolytic Anemia" as your search term in the Rare Disease Database.)

Thalassemia major (Cooley's anemia or Mediterranean anemia) is characterized by a marked increase in F hemoglobin, a decrease of proteins within hemoglobin and an abnormally low level of red blood cells. Thalassemia major is the most severe form of chronic familial hemolytic anemias and is primarily in people with Mediterranean ancestry. The onset of symptoms is usually rapid and may occur during infancy or early childhood. Symptoms may include generalized weakness, overall feeling of illness (malaise), an upset stomach (dyspepsia), heart palpitations, a yellow color to the skin (jaundice) and/or leg sores. Other symptoms may include an enlarged liver (hepatomegaly), an enlarged spleen (splenomegaly), inflammation of the gall bladder (cholelithiasis), and/or an enlarged abdomen. Children with thalassemia major may have heart problems and they may be short for their age due to bone problems. (For more information on this disorder, choose "Thalassemia Major" as your search term in the Rare Disease Database.)

Thalassemia minor is a relatively mild form of anemia that is typically present at birth. It is inherited as an autosomal recessive genetic trait. Constant fatigue may be the only symptom of this disorder. However, if anemia becomes severe, the spleen may become slightly enlarged (splenomegaly) and there may be a pale color to the skin. Occasionally a child with Thalassemia minor may complain of pain in the left upper side of the abdomen. This disorder may be aggravated by stress, infections, malnutrition, and/or pregnancy. (For more information on this disorder, choose "Thalassemia Minor" as your search term in the Rare Disease Database.)

Other types of anemias include: aplastic anemia; hereditary non- spherocytic hemolytic anemia; megaloblastic anemia; warm antibody hemolytic anemia; cold antibody hemolytic anemia; acquired autoimmune hmolytic anemia; pernicious anemia; folic acid deficiency anemia; blackfan-diamond anemia; and Fanconi's anemia. For information on other types of anemias, choose "Anemia" as your search term on the Rare Disease Database.

Standard Therapies

Diagnosis
Two tests are used to screen for sickle cell disease in newborn infants. Umbilical cord blood screening is used to detect sickle cell disease in newborns. Hemoglobin testing (electrophoresis) can detect the major varieties of sickle cell disease. As part of routine newborn screening in most US states, newborns are screened for hemoglobin S (the defective, sickle-shaped form of hemoglobin characteristic of the disorder).

Treatment
The treatment of sickle cell disease is symptomatic and supportive. People with sickle cell disease must get regular medical checkups, avoid chills, dress warmly, eat nutritionally balanced meals, get adequate sleep, avoid standing in the cold without exercising, and practice deep breathing for five minutes before going to sleep. Vaccination against pneumococcal infections may be given to children over the age of two years.

Pain-relieving medications may be administered during painful crises. Blood transfusions are often used to reduce the risk of a stroke in an affected individual and to treat anemia. Folic acid may also be used to treat individuals with anemia. In some cases, surgery may be necessary because of damage to specific organs such as gall bladder surgery to remove gall stones or surgical removal of the spleen (splenectomy) to treat splenic crisis.

Genetic counseling will be of benefit for affected individuals and their families. Genetic testing can determine if a person is carrying the sickle cell trait. In general if a couple both have the sickle cell trait they have a 25 percent chance of having a child with sickle cell disease.

The drug hydroxyurea (Hydrea or Droxia) has been approved by the Food and Drug Administration (FDA) for the treatment of sickle cell disease. Hydroxyurea helps stimulate the production of fetal hemoglobuin. Hydroxyurea is manufactured by Bristol-Myers Squibb Company.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Phase III clinical trials are being launched (2006) for denufosol, an early intervention therapy for treatment of patients with mild lung disease. For information on this drug, contact the manufacturer:

Inspire Pharmaceuticals
4222 Emperor Boulevard, Suite 200
Durham, NC 27703
Tel.: (919) 941-9777
Fax: (919) 941-9797

In January 2004, the U.S. Food and Drug Administration (FDA) designated oral unfractionated heparin an orphan drug for the treatment of sickle cell disease. The drug's manufacturer is TRF Technologies, Inc. For information, contact:

TRF Technologies, Inc.
108 Eagle Trace Drive
Half Moon Bay, CA 94019
Phone: (650) 727-0110
Fax: (650) 727-8637
Email: sembury@trftech.com

Research results released in April 2003 showed that hydroxyurea improved survival rates among people who were severely affected by sickle cell anemia. Specifically, the study showed a 40 percent reduction in deaths among patients who took the drug over a nine-year period. These results were announced through the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, sponsor of the research.

Previous research had shown that hydroxyurea reduced symptoms among the most severely affected sickle cell patients. The more recent research shows that the drug also improves the survival of the sickest patients.

In other research, scientists at the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) are studying whether inhaling nitric oxide gas mixed with room air can improve pulmonary hypertension (high blood pressure in the lungs) in patients with sickle cell disease. It is estimated that 20 to 30 percent of patients with this disease have moderate to severe pulmonary hypertension. Patients 18 and older may be eligible. Contact:

NHLBI Patient Recruitment and Public Liaison Office
9000 Rockville Pike
Bethesda, MD 20892
Telephone: (800) 411-1222
Email: prpl@mail.cc.nih.gov

The NHLBI is also funding research into a study called Stroke With Transfusions Changing to Hydroxyurea (SWITCH). The study aims to determine whether hydroxyurea can replace blood transfusions and whether monthly blood withdrawal can replace daily injections to treat iron overload. The study is currently in Phase III clinical trials.

Flocor is designated an orphan drug by the U.S. Food and Drug Administration (FDA). The most common problem sickle cell patients face is episodic pain (also referred to as vaso-occlusive crisis). Flocor is being studied for its ability to reduce the duration of these episodes by improving blood flow. The sponsoring company is the CytRx Corporation of Los Angeles, CA.

In May 1998, fructose-1, 6-diphosphate (Cordox) received orphan drug designation as a treatment for painful vaso-occlusive episodes associated with sickle cell disease. Cordox is manufactured by Questcor Pharmaceuticals, Inc., of Union City, CA.

Bone marrow and cord blood stem cell transplantation are being studied for treatment of sickle cell disease. Sites of this research include the Fred Hutchinson Cancer Research Center in Seattle, WA, and Boston University.

Organizations related to Sickle Cell Disease

References

TEXTBOOKS
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:.

Bennett JC, Plum F., eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:

Hoffman R, et al., eds. Hematology Basic Principles and Practice, 2nd ed. New York, NY: Churchill-Livingstone, Inc; 1995:

Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1658-60.

Research Resources Reporter, National Institutes of Health, June 1991. Pp. 10-11.

JOURNAL ARTICLES
Gladwin M. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med. 2002;12:1383-89.

Rescorla FJ, et al. Laparoscopic splenectomy has become the gold standard in children. Am Surg. 2002;68:297-301.

Sandoval C, et al. Perioperative management in children with sickle cell disease undergoing laparoscopic surgery. JSLS. 2002;6:29-33.

Miller ST, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. 2000;342:83-89.

Cohen AR. Sickle cell disease - new treatments, new questions. N Engl J Med. 1998;339:42-44.

Adams RJ, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultrasonography. N Engl J Med. 1998;339:5-11.

Franklin Bunn H. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997;337:762-69.

Lubin BH. Sickle cell disease and the endothelium. N Engl J Med. 1997;337:1623-25.

Solovey A, et al. Circulating activated endothelial cells in sickle cell anemia. N Engl J Med. 1997;337:1584-90.

Walters MC, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med. 1996;335:369-76.

Platt OS, et al. Bone marrow transplantation in sickle cell anemia - the dilemma of choice. N Engl J Med. 1996;335:426-27.

Charache S, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995;332:1317-22.

Schechter AN, et al. Sickle cell anemia - basic research reaches the clinic. N Engl J Med. 1995;332:1372-74.

Eaton WA, et al. The biophysics of sickle cell hydroxyurea therapy. Science. 1995;268:1142-43.

Bellet PS, et al. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med. 1995;333:699-703.

Steingart R. Management of patients with sickle cell disease. Med Clin North Am. 1992;76:669-80.

Powers DR. Sickle cell anemia and major organ failure. Hemoglobin. 1990;14:573-598.

Perrine SP, et al. A short-term trial of butyrate to stimulate fetal-globin-gene expression in the B-globin disorders. N Engl J Med. 1993;328:81-86.

FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:603903; Last Update:4/8/02.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/09 00:00:00 GMT+0

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