News Release: Emory Healthcare , Research , School of Medicine

Jun. 22,  2010

NIH Awards Grant to Emory Researchers to Study Effects of Stored Red Blood Cells on Transfusions

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has awarded researchers at Emory University a four-year, $1.7 million grant to study the effects of blood storage on the efficacy of red blood cell transfusions.

Led by John Roback, MD, PhD, associate professor of pathology and laboratory medicine and director of the Emory University Hospital blood bank, the project will study how red blood cell preparation methods and storage times affect nitric oxide levels, blood flow and the amount of oxygen absorbed by patients' tissues. It will also investigate whether cardiovascular disease patients, who may have difficulty producing and responding to nitric oxide, are more sensitive to effects of stored and processed blood than are patients without cardiovascular disease. Co-investigators include Roy Sutliff, PhD, and Arshed Quyyumi, MD.

Transfusion of red blood cells is often used in critically ill patients with low red blood cell counts to prevent disease progression and death. According to Roback, recent studies suggest that the use of "aged" versus "fresh" red blood cells is associated with worse clinical outcomes, although the results are controversial. Other studies have argued that there is no discernable effect of blood storage on patient outcome. The Food and Drug Administration currently allows blood stored up to 42 days to be used in transfusions.

"There is evidence that when red blood cells ‘sense' low oxygen levels in tissues they release signals that cause surrounding blood vessels to dilate, thereby increasing the local blood flow," says Roback. "One substance that has been implicated as a signal between red blood cells and the vessel wall is nitric oxide. We are trying to determine whether the nitric oxide signal between red blood cells and blood vessels is altered because of different blood processing and storage techniques.

"One of our hypotheses is that "aged" red blood cells may produce less nitric oxide, or actually block the nitric oxide signal, thereby preventing arterial relaxation. This effect would reduce the blood supply to organs in need," says Roback. "In addition to determining whether storage time affects red blood cell interactions with blood vessels, these studies are also designed to further optimize the methods we use for storing and processing blood prior to transfusion."

The project will be broken down into three different phases.

The first phase will investigate the effects of blood processing and storage in an organ bath environment. Blood samples are incubated with a segment of rat aorta in order to determine the immediate effects of each red blood cell solution on blood vessel relaxation. Modifications such as washing and rejuvenation will be investigated as possible approaches to correct abnormalities in nitric oxide bioavailability.

The second series of studies will involve transfusing healthy volunteers to investigate the effects of storage-related red blood cell changes on blood flow and tissue oxygenation.

The third phase will seek to determine the effects of transfused red blood cells in patients with endothelial dysfunction due to cardiovascular disease. A non-invasive ultrasound device will be used to test whether patients with cardiovascular disease and endothelial dysfunction are more susceptible to effects from stored/processed red blood cells than fresh red blood cell units. Vasodilation and tissue oxygenation in response to transfusion will be monitored, and Framingham risk scores and cardiovascular disease biomarkers will be tested as potential predictive factors to identify patients most at risk from adverse effects of RBC transfusions.

The NHLBI is funding a total of nine research grants to determine if the safety and efficacy of red blood cell transfusions vary depending on how long the cells have been stored.

Studies have shown that blood processing and storage cause several changes in red blood cell units, including lower concentrations of molecules that regulate how oxygen is delivered to patients' tissues. Storage and preparation also affect the deformability of red blood cells. Deformability normally allows the cells to squeeze through capillaries half their size.

Despite these documented changes in red blood cells during storage, scientists do not fully understand the causes, extent and timing of these changes, or if they affect transfused patients' health. Recent research on patient outcomes has yielded conflicting results. For example, some studies suggest that red blood cells stored for longer periods of time are less effective and more likely to harm transfusion recipients. They associate older stored red cells with more complications and deaths among heart surgery patients, trauma patients, and critically ill patients in the intensive care unit. In contrast, other investigations have found no differences in clinical outcomes using red cells stored short-term or long-term.

U.S. medical workers administer about 14.7 million units of blood to about five million patients each year. These transfusions contain red blood cells to treat patients with anemia or to replenish blood lost to surgery or severe injury.

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The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.

Learn more about Emory’s health sciences:
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Web: http://emoryhealthsciences.org

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