Sickle cell anemia is one of the most common genetic diseases worldwide. In the United States sickle cell disease affects some 50,000 African Americans. It is also seen in some Mediterranean countries and in the Caribbean, Central and South America and India.

Sickle cell disease is caused by a defect in the gene that makes hemoglobin, the molecule in red blood that transports oxygen to the body’s cells. The defect causes hemoglobin molecules to stick together so that blood cells lose their flexible, disc-shaped form and become long, curved and more rigid, taking on the sickle shape for which they are named.

The sickle cells tend to clump together, sticking to the walls of blood vessels and causing blockages that inhibit blood flow to surrounding tissues. Blocked blood vessels in the arms, legs or chest result in tissue and organ damage as well as severe pain.

Sickle cell disease occurs in about one of every 375 African American newborns. One of every 12 African American infants is born carrying the sickle cell trait, but simply being a carrier of the HbS gene has no effect on health or life expectancy. If two people who are carriers have a child, however, the child has a 25 percent chance of having sickle cell disease, a 50 percent chance of being a carrier of the trait and a 25 percent chance of being free of both the disease and the trait.

The last two decades have seen big changes in managing sickle cell disease. If not diagnosed and treated early, infants with sickle cell disease face a high risk of serious illness or even death in the first few years of life. As a result almost all states have screening programs to identify newborns with the disease.

Infants diagnosed with sickle cell disease are treated with penicillin therapy beginning shortly after birth and are immunized in a timely manner with pneumococcal and H. influenzae vaccines. These measures protect infants against many of the infections and illnesses that threaten sickle cell babies.

Treatment Targets Pain
Pain crises are a hallmark of sickle cell disease in both adults and children. Painful episodes, precipitated by decreased blood flow to certain areas of the body, often last up to a week and for some patients can occur a number of times in a year.

Pain levels during these crisis periods vary from episodes that a patient may be able to manage at home to excruciating pain that needs to be managed in a hospital.

When pain can be managed at home patients usually work with their physician who might monitor their use of over-the-counter pain killers such as aspirin or ibuprofen or prescribe more powerful painkillers if needed. Patients are usually advised to drink plenty of fluids, rest and keep warm.

Severe pain crises are usually managed in hospital settings where patients are given more powerful drugs such as intravenous morphine as well as fluids to improve hydration. Psychosocial support is also important for patients and family members during these difficult periods.

Not all sickle cell disease patients experience such severe pain crises. Those who have the most frequent and severe crises face a higher risk of serious and even fatal complications from stroke, acute chest syndrome and organ failure.

The drug hydroxyurea is the only approved treatment for sickle cell disease although others are currently being tested. Treatment with hydroxyurea reduces the incidence of painful episodes and of pneumonia by up to 50 percent. One study found that it reduced mortality in patients by about 40 percent over a period of six to eight years.

Another drug, purified polaxamer 188 (PP188) has shown promise in trials. A trial involving 255 patients aged between 9 and 53 years treated with PP188 found that 52 percent achieved resolution of pain crisis within five days compared with 37 percent of those receiving a placebo drug. PP188 improves microvascular blood flow by decreasing the tendency of the blood to stick to vessel walls.

Other treatments for sickle cell patients include regular blood transfusions, but the effectiveness of transfusion is limited by the tendency to cause iron overloading.

The hope for a future cure for sickle cell disease lies with gene therapy. Scientists have successfully replaced the defective HbS gene in mice, but human trials are still in the future.

It is possible to cure sickle cell disease using bone marrow transplantation, but the procedure carries a high level of risk and as a result is reserved only for the sickest patients. Suitable donor matches are difficult to find and one in ten patients dies, either as a result of infection or because of rejection of the donor marrow.

Trials to replace only a portion of the bone marrow have shown promise in mice, and may offer a viable alternative in the future.

Patient education is important with sickle cell disease. Although it may be impossible to eliminate pain crises, there are a number of steps patients can take to lower their risk.

• Avoid exposure to cold. Dress warmly in winter and in air conditioned spaces in summer. Avoid swimming in cold water.
• Don’t smoke.
• Avoid drinking excess alcohol.
• Avoid overexertion.
• Avoid dehydration by drinking plenty of fluids.
• Don’t fly in unpressurized aircraft.
• Try to control stress.

Parents of children with sickle cell disease need to protect them from cold, dehydration and overexertion. They also should be alert for infections, pain, breathing problems, high temperatures, swelling of the hands and feet, and sudden enlargement of the spleen (physicians often teach parents to palpate for this). They should seek medical care if any of these conditions develop.

Prenatal testing of fetal blood can diagnose sickle cell disease in utero and parents can receive counseling about the condition.

A costly option for couples with a risk of bearing a child with sickle cell disease is preimplantation diagnosis.. This technique uses in vitro fertilization and DNA testing of embryos to select only those free of the disease for implantation.

Advances in gene therapy suggest that a cure for sickle cell disease may be possible in the not-too-distant future. In the meantime vigilance on the part of patients and families aimed at minimizing painful crises and the development of new drugs can help manage the disease for the present.

REFERENCES:
Sherry Boschert, “Sickle Cell Deaths Down by 40 Percent in Hydroxyurea Users,” Family Practice News, February 1, 2001.
Deborah Kaplan, “Helping Patients Through a Sickle Cell Crisis,” Patient Care, December 30, 2001.
Kurt Kleiner, “Mixed Blood,” New Scientist, June 23, 2001.
William Mentzer and Yuet Wai Kan, “Prospects for Research in Hematologic Disorders–Sickle Cell Disease and Thalassemia,” JAMA, February 7, 2001
Mary Ann Moon, “Experimental Drug Shortens Sickle Cell Crises,” Pediatric News, April 2002.
Ronald Nagel, “The Challenge of Painful Crisis in Sickle Cell Disease,” JAMA, November 7, 2001.
“Practical Tips for Preventing a Sickle Cell Crisis,” American Family Physician, March 1, 2000.
“Sickle Cell Disease,” American Family Physician, September 1, 2000.
Joan Stephenson, “Sickle Cell Gene Therapy,” JAMA, January 9, 2002.
“Update: Newborn Screening for Sickle Cell Disease,” JAMA, September 20, 2000.
D.J. Weatherall and A.B Provan, “Red Cells 1: Inherited Anemias,” The Lancet, April 1, 2000.
Doris L. Wethers, “Laboratory Diagnosis, Pathophysiology and Health Maintenance, (Sickle Cell Disease in Childhood), American Family Physician, September 1, 2000.