A treatment that prevents strokes in children with sickle cell anemia was announced today by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.
A clinical alert was issued to U.S. physicians who treat children with sickle cell anemia to advise them of new data from the "Stroke Prevention Trial in Sickle Cell Anemia" (STOP). The data show that administering blood transfusions every three-to-four weeks to children with sickle cell anemia who are at high risk for stroke reduces their rate of stroke by 90 percent. The results were so compelling that the study was stopped on August 29 -- 16 months earlier than planned.
The announcement was made at a national conference on sickle cell disease, commemorating the 50th Anniversary of the NHLBI and the 25th Anniversary of its Sickle Cell Disease Program.
"This is very good news for the roughly 2,500 children with sickle cell anemia who may be at risk for stroke and their families," said NHLBI Director Dr. Claude Lenfant. "Although this is not a cure, transfusions offer these children the hope of avoiding the devastating consequences of stroke."
"Of course, blood transfusions have their own risks," he added. "But for the patients and their families, the benefits of preventing strokes and their debilitating effects far outweigh the risks associated with repeated blood transfusions. And we continue to support research to develop other agents that will prevent strokes with fewer complications." Approximately 10 percent of children with sickle cell anemia experience strokes, which are among the most serious complications of this disease. Strokes can cause motor and neuro-psychological impairment, affecting a child's ability to move, speak, and learn. Once a child with sickle cell anemia has had a stroke, his or her risk of having another is roughly 80 percent.
In the Stroke Prevention Trial, 130 children with sickle cell anemia, found to be at high risk of stroke by transcranial doppler screening, were recruited from 14 U.S. and Canadian sickle cell centers between February 1995 and October 1996. The children were ages 2-16. Sixty-three children received blood transfusions every three-to-four weeks to keep the amount of abnormal, or sickle, hemoglobin in their blood to no more than 30 percent of total hemoglobin. The other 67 children received standard supportive care for sickle cell anemia.
After one year, the rate of strokes in the group treated with transfusions was 90 percent less than that in the standard care group (10/67 - 14.9% standard care group vs, 1/63 - 1.5% transfusion group). This difference was significant enough to establish that the treatment should be considered for all children with sickle cell anemia who are at high risk for stroke.
Transcranial doppler (TCD) screening was used to identify children at risk for stroke for the study. This is an ultrasound technique that measures the velocity of blood flow in the brain.
High blood flow velocities in one or more major arteries of the brain are thought to indicate a significant narrowing in key blood vessels supplying the brain, which markedly increases the risk of a stroke. The TCD instrument for the study has been used for years to screen adults for increased risk of stroke and was adapted for use in children with sickle cell disease by Dr. Robert Adams, principal investigator of STOP and Professor of Neurology, Medical College of Georgia.
Dr. Adams says, "Once we demonstrated that TCD could identify children at risk for stroke, we no longer had to wait for these children to have a stroke before we could treat them. The STOP results are exciting because they show that we can now intervene before brain damage from stroke takes place and actually prevent the stroke."
The children in the transfusion arm were monitored for transfusion-associated complications. At this point, there is no evidence that any of them contracted a transfusion-transmitted virus during the study, but 9 patients developed antibodies to proteins in the blood, which complicates the task of finding matching blood for future transfusions. Most of the children also developed excess levels of iron, which can be harmful to several vital organs and must be treated with a procedure called chelation therapy. This is a painful, inconvenient, and expensive process involving ongoing subcutaneous infusions of a drug that removes the iron. Children with sickle cell anemia who receive transfusion therapy to prevent strokes will probably require long-term chelation therapy.
Sickle cell anemia is the most common genetic blood disorder in the U.S., affecting approximately 1 in 500 African-American and 1 in 1,000 Hispanic newborns each year. In patients with the disease, abnormal hemoglobin molecules in the red blood cells tend to damage the red cell walls, causing them to stick to blood vessel walls. This can result in the development of narrowed, or blocked, blood vessels in the brain, causing a stroke. This type of stroke, which is called a cerebral infarction, occurs primarily in children.
The participating centers in STOP were:
- Children's Hospital of Eastern North Carolina, Greenville, NC;
- Children's Hospital of Oakland, Oakland, CA;
- Children's Mercy Hospital, Kansas City, MO;
- Children's National Medical Center, Washington, DC;
- Columbia Presbyterian Hospital, NYC;
- Emory University, Atlanta, GA;
- Hospital for Sick Children, Toronto, Ontario;
- Medical College of Georgia, Augusta, GA;
- Medical University of South Carolina, Charleston, SC;
- Rainbow Babies & Children's Hospital, Cleveland, OH;
- State University of New York, Brooklyn, NY;
- St. Jude's Children's Research Hospital, Memphis, TN;
- Tulane Medical University, New Orleans, LA; and the
- University of Miami Medical School, Miami, FL.
Medical College of Georgia was the Central Administrative Center, and New England Research Institutes, Watertown, MA was the Data Coordinating Center.
The National Heart, Lung, and Blood Institute is a component of the National Institutes of Health, U.S. Department of Health and Human Services.