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Regular blood transfusions can reduce repeat strokes in children with sickle cell disease

Date:
August 20, 2014
Source:
Vanderbilt University Medical Center
Summary:
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 study results. Sickle cell disease most commonly affects African-Americans, occurring in one of every 396 births in this ethnic group. In the disease, red blood cells are 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.

Vanderbilt-led research, as part of an international, multicenter 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 study results released today in the New England Journal of Medicine (NEJM).

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Michael R. DeBaun, M.D., MPH, director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence and professor of Pediatrics, was the principal investigator of the more than $20 million, federally-funded trial, the largest of its kind in children with sickle cell. 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 including pain 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 3 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.

Results of the 10-year trial led by DeBaun, which involved 29 clinical centers in the United States, France, Canada and the United Kingdom, appear in the Aug. 21 issue of NEJM.

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. The actual benefit of transfusion therapy is probably higher because 15 percent of the children who were assigned to receive blood transfusion therapy either never received the transfusion or only received transfusions for a brief period, but were counted as if they were transfused, referred to as "intention to treat analysis."

"The success of the trial is a tribute to over 1,000 families of children who were screened with an MRI of the brain and the almost 200 families of children who committed to monthly visits for three years. The successful recruitment, adherence and retention of black families, many of whom were working poor, to an arduous, complex trial, should lay to rest the misperception that blacks are not willing participants in research," said DeBaun, J.C. Peterson M.D. Professor of Pediatric Pulmonology.

"The results of the trail indicate members of the community are interested in research, when they are well-informed, empowered to make their own decision, and have a trusting relationship with the health care provider who is independent of their participation in the study," DeBaun continued. "Secondary benefits of this trial include the significant improvement in clinical care for children with sickle cell disease at each of the 29 sites because each location had a designated hematologist, neurologist, neuroradiologist and psychologist working as a team to identify and decrease further injury to the brain in this vulnerable population."

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. They were randomly assigned to the transfusion group or the observation group. Average length of participation was three years. The children in the transfusion group were 58 percent less likely to suffer a repeat silent stroke or stroke than the observation group. Of the 99 children who received transfusions, 6 percent had an overt stroke or suffered a new or enlarged silent stroke. Whereas 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.

"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 painful episodes and acute chest syndrome. The results of this trial will make a difference to children with sickle cell anemia and their families," said Deborah Hirtz, M.D., program director at the National Institute of Health's National Institute of Neurological Disorders and Stroke (NINDS).

However, the benefits of the transfusion therapy must be weighed against the risks of excessive iron stores, transfusion reactions and the burden of missed work and school days. Further research is needed, the study states, to identify which children with history of silent strokes are at greatest risk for recurrence so transfusion therapy can be targeted to them.


Story Source:

The above story is based on materials provided by Vanderbilt University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Michael R. DeBaun, Mae Gordon, Robert C. McKinstry, Michael J. Noetzel, Desiree A. White, Sharada A. Sarnaik, Emily R. Meier, Thomas H. Howard, Suvankar Majumdar, Baba P.D. Inusa, Paul T. Telfer, Melanie Kirby-Allen, Timothy L. McCavit, Annie Kamdem, Gladstone Airewele, Gerald M. Woods, Brian Berman, Julie A. Panepinto, Beng R. Fuh, Janet L. Kwiatkowski, Allison A. King, Jason M. Fixler, Melissa M. Rhodes, Alexis A. Thompson, Mark E. Heiny, Rupa C. Redding-Lallinger, Fenella J. Kirkham, Natalia Dixon, Corina E. Gonzalez, Karen A. Kalinyak, Charles T. Quinn, John J. Strouse, J. Philip Miller, Harold Lehmann, Michael A. Kraut, William S. Ball, Deborah Hirtz, James F. Casella. Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia. New England Journal of Medicine, 2014; 371 (8): 699 DOI: 10.1056/NEJMoa1401731

Cite This Page:

Vanderbilt University Medical Center. "Regular blood transfusions can reduce repeat strokes in children with sickle cell disease." ScienceDaily. ScienceDaily, 20 August 2014. <www.sciencedaily.com/releases/2014/08/140820183456.htm>.
Vanderbilt University Medical Center. (2014, August 20). Regular blood transfusions can reduce repeat strokes in children with sickle cell disease. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2014/08/140820183456.htm
Vanderbilt University Medical Center. "Regular blood transfusions can reduce repeat strokes in children with sickle cell disease." ScienceDaily. www.sciencedaily.com/releases/2014/08/140820183456.htm (accessed November 28, 2014).

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