Discovering Hope

Transfusions ease strokes for children with sickle cell

Vanderbilt-led research, as part of an international, multi-center trial, found regular blood transfusion therapy significantly reduces the recurrence of silent strokes and strokes in children with sickle cell anemia who have had pre-existing silent strokes, according to results published in the New England Journal of Medicine (NEJM).

Michael R. DeBaun, M.D., MPH, director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, professor of Pediatrics, and J.C. Peterson M.D. Professor of Pediatric Pulmonology, was the principal investigator of the more than $20 million, federally funded trial, the largest of its kind in children with sickle cell. The 10-year trial involved 29 clinic centers in the United States, France, Canada and the United Kingdom.

Nearly 100,000 people in the United States are living with sickle cell disease, a group of inherited blood disorders. Sickle cell disease most commonly affects African-Americans, occurring in one of every 396 births in this ethnic group. In patients with the disease, red blood cells are abnormal—hard, sticky and shaped like a crescent moon. When the sickle cells travel through small blood vessels, they can decrease the normal blood flow to all organs of the body, causing many complications that require hospitalization for treatment, lung disease and a shortened life span.

Silent strokes are frequent in sickle cell anemia (the most common form of sickle cell disease), occurring in approximately 30 percent of school-age children with the disease, and can cause poor school performance and limit performance of complex tasks. The only way to diagnose a silent stroke is with magnetic resonance imaging (MRI) of the brain. Once a child has had a silent stroke, he is at a much higher risk for more dangerous overt strokes and new or enlarged silent stokes.

The Silent Cerebral Infarct Transfusion (SIT) Trial looked at the efficacy of blood transfusion therapy for children with sickle cell anemia to prevent repeat cerebral infarcts (overt strokes and silent strokes). Researchers found that monthly blood transfusions reduced the recurrence of silent strokes and strokes by 58 percent in children with pre-existing silent strokes when compared to children who were not transfused.

Participants in the single-blind study included 196 children, between ages 5 and 15, who had no history of stroke, but had one or more silent strokes confirmed by MRI.

Of the 99 children who received transfusions, 6 percent had an overt stroke or suffered a new or enlarged silent stroke. But in the observation group, 14 percent of the 97 children had a cerebral infarct, meaning they were more than twice as likely to suffer a repeat event without monthly transfusion therapy. But in the observation group, 14 percent of the 97 children had a cerebral infarct, meaning they were more than twice as likely to suffer a repeat event without monthly transfusion therapy.

Given the positive findings of the study, DeBaun and other authors of the study recommend that children with sickle cell anemia have a surveillance MRI, preferably without sedation, by the beginning of elementary school. Most children with the disease who are at risk for a silent stroke will have one by age 6.

Additionally, the study notes health care providers should discuss treatment options with families to determine if transfusion therapy is appropriate when a silent stroke is detected.

DeBaun’s clinical and research programs receive support from the Junior League of Nashville.

The National Institute of Health’s National Institute of Neurological Disorders and Stroke was the primary source of funding for this 10-year trial under grant numbers (5U01NS042804, 3U01NS042804).

– by Christina Echegaray