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Monthly Blood Transfusions Reduce Sickle Cell Anemia-related Brain Injury in Children

Published: Friday, August 22, 2014
Last Updated: Friday, August 22, 2014
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NIH-funded study provides hope for children with disease-related brain damage.

Regular blood transfusions prevent recurrent blockage of brain blood vessels, a serious neurological side effect that occurs in one third of children with sickle cell anemia, according to a study funded by the National Institutes of Health. The findings appear in the August 21 issue of the New England Journal of Medicine.

In the United States, approximately 100,000 people, primarily African-Americans, live with sickle cell anemia, a genetic disorder in which red blood cells, which should be round, can take on abnormal, crescent-like shapes. These sickle cells are stickier than regular cells and can block blood flow, resulting in pain, organ damage and strokes.

Cerebral infarcts occur when blood vessels in the brain get blocked. Silent cerebral infarcts do not cause any obvious symptoms, so people are unaware that something is wrong. The only way to detect a silent stroke is with magnetic resonance imaging (MRI) scans of the brain, which are not routinely conducted in people with sickle cell anemia. Silent infarcts in children with sickle cell disease are known to be associated with long-term cognitive problems and poor academic performance.

“If scientists detect silent strokes early, young children can benefit from a wide array of educational interventions and can get support from federally mandated educational assistance programs to keep them from falling behind in school,” said Michael R. DeBaun, M.D., from Vanderbilt University, Nashville, the lead author and principal investigator for the trial.

Previous studies have demonstrated that blood transfusions may help prevent stroke in patients with sickle cell anemia. Transfusions of healthy blood increase the number of normal red blood cells and make the occurrence of blocked blood vessels less likely. In the current study, Dr. DeBaun and his colleagues investigated whether monthly blood transfusions would help prevent recurrence of silent cerebral infarcts in children with sickle cell anemia who had evidence of a previous incident.

In this multi-center international clinical trial, 1,074 children had MRI scans and 35 percent had silent infarcts. The 196 children with sickle cell anemia who exhibited infarct-like lesions on brain scans were randomized to receive regular blood transfusions or standard medical care. The blood transfusions were administered every month for three years.

The investigators’ results show that receiving blood transfusions on a regular basis prevented the recurrence of silent strokes. In the standard medical care group, 14.4 percent of patients experienced a stroke or new silent cerebral infarcts. Among patients who received regular blood transfusions, only 6.1 percent experienced a stroke or new silent cerebral infarct.

“The study provides clear evidence that we may be able to decrease the progression of silent strokes, which occur in 30 percent of children with sickle cell anemia. These results suggest that children who have this disease should be screened early for silent strokes, at least by the time they begin elementary school, to help them manage the disease and to ensure minimal impact on school performance,” said Dr. DeBaun.

The researchers noted that this trial included a very intense regimen for the patients, who were as young as 5 years old, and for their families. “One of the reasons we conducted this study was to check if the burden of the blood transfusion therapy, such as monthly doctor’s visits, was worth the potential benefits,” said Deborah Hirtz, M.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke, which provided funding for the study. Some risks linked to blood transfusions include severe allergic reactions and high levels of iron throughout the body.

“The commitment of the children and their parents, many of whom were working poor families, was quite impressive. Despite the burden of a three-year intensive trial, 86 percent of the participants completed all aspects of the trial including 36 months of transfusion therapy, three non-sedated MRI scans, multiple neurology evaluations, two two-hour cognitive testing sessions, and two quality of life assessments,” said Dr. DeBaun.

An unexpected result, according to the researchers, was that intelligence measures were not different between the two study groups. Previous studies from this trial and others have shown that silent strokes are associated with a five-point reduction in IQ. This issue will be further explored by the investigators.

“The study indicates that screening for silent strokes in children starting school can lead to early detection and prevention of recurrences as well as reduction in other complications of sickle cell anemia such as acute episodes of pain and acute chest syndrome. The results of this trial will make a difference to children with sickle cell anemia and their families,” said Dr. Hirtz.

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