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Children with sickle cell disease, silent strokes show some relief with blood transfusions

A group of children who have sickle cell disease and who experience silent strokes showed some relief from the silent strokes with blood transfusion therapy, researchers at Washington University School of Medicine in St. Louis have found.

The study's results will appear in a future issue of Pediatric Blood and Cancer but are available for review in its advance online publication.

In a Phase II study of 10 children with sickle cell disease who also had multiple silent strokes, or cerebral infarcts, the majority of families were committed to having their children receive blood transfusions for two years, showing that the therapy was feasible. In addition, the blood transfusion therapy helped to shrink the lesions on the brain caused by the infarcts and eliminated one lesion completely, said Allison A. King, M.D., a pediatric hematologist at St. Louis Children's Hospital and a researcher at Washington University School of Medicine. Lesions are small areas of damaged tissue thought to be due to blockage of small arteries in the brain.

Silent strokes are strokes that don't show the classic symptoms of overt strokes, such as numbness, tingling, headache or slurred speech. Blood transfusion therapy has been shown to be effective in preventing overt strokes in patients with sickle cell disease, but its effectiveness and the willingness of families to participate in long-term treatment to prevent silent strokes had not been tested.

Sickle cell disease is an inherited blood disorder affecting red blood cells that contain hemoglobin, a substance that carries oxygen from the air in the lungs to all parts of the body. In patients with this disease, red blood cells contain an abnormal type of hemoglobin that causes the normally round, flexible red blood cells to become sickle- or crescent-shaped. The sickle cells can't pass through tiny blood vessels, preventing blood from reaching the body's tissues, which can result in tissue and organ damage, pain and stroke.

Sickle cell disease affects about 70,000 people in the United States. It occurs in about 1 of every 500 African-American births and 1 of every 1,000 to 1,400 Hispanic-American births. While there is no cure for the disease, blood transfusions and bone marrow transplants have been shown to be effective treatments by replacing short-lived sickle cells with longer-lived healthy red blood cells, although bone marrow transplants have a 10 percent mortality rate because of the possibility of rejecting the bone marrow, complications such as seizures and a high risk of infection.

In the study, brain lesions in six patients shrank after two years of regular blood transfusions, and no new silent strokes occurred. One patient had a lesion disappear, however, that patient did not continue with further blood transfusions, and the lesion returned at more than three times its original size, suggesting the need for prolonged transfusions. A lesion grew larger in the seventh patient.

Many of the lesions occur in the frontal lobe of the brain, which controls the cognitive function or problem-solving area, or in the occipital lobe, which controls the visual processing center, King said. Neuroradiologists can locate the lesions using magnetic resonance imaging (MRI).

"Because these lesions are usually in the frontal lobe, it is important to do cognitive testing on these children to determine any impairment," King said. "We hope that by preventing further lesions through blood transfusions that we can preserve their ability to think and learn."

A total of 71 percent of the school-aged children in the study were receiving special education services and 57 percent had failed a grade in school. Previous School of Medicine research shows that 80 percent of students with silent strokes perform poorly in school.

King said the results of the trial were encouraging to health-care professionals treating children with sickle cell disease.

"What we found in this trial is that families and children with sickle cell disease and who experience silent strokes are willing to commit to blood transfusion therapy for this condition," King said. "If these children are left untreated, their risk for an overt stroke is very high, but if we use blood transfusion therapy, they may have a lower risk for overt stroke and no evidence of new silent infarcts on an MRI."

Results of this Phase II trial spearheaded a larger, Phase III study that is evaluating 1,800 children in the United States, Canada and Europe. That trial, called the Silent Cerebral Infarct Multi-Center Clinical Trial, is headed by Michael R. DeBaun, M.D., professor of pediatrics at the School of Medicine. Through it, researchers will further determine the effectiveness of blood transfusion therapy to prevent silent strokes in children with sickle cell disease and to prevent further cerebral injury.


Contact: Beth Miller
Washington University School of Medicine

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