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 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.
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.
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.
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).
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.
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
For information about clinical trials sponsored by private sources, contact:
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:
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
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
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.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:603903; Last Update:4/8/02.