Issue Date: February 3, 2014
Better Way To Feed Red Blood Cells
Efforts to improve blood banking have focused on extending the shelf life of red blood cells. Those efforts have succeeded: The length of time red blood cells can be stored in the U.S. has progressively increased from 21 days to 35 days to the current standard of 42 days.
But that increased storage time has a downside when it comes to blood transfusions. “Recently, there have been a number of reports suggesting that older red cells are less effective—even less safe—than fresher red cells,” says Jerry E. Squires, the medical director of transfusion medicine at Medical University of South Carolina.
Red blood cells are best known for their role in carrying oxygen, but they have other jobs too. For example, they release adenosine triphosphate (ATP), which causes blood vessels to release nitric oxide and dilate, a necessity for maintaining normal blood flow. Several studies have found that stored red blood cells induce less nitric oxide production than do fresh red blood cells.
Recent work by chemistry professor Dana M. Spence and graduate students Yimeng Wang and Adam Giebink of Michigan State University suggests that these problems with older red blood cells could be caused by the solutions those cells are stored in (Integr. Biol. 2013, DOI: 10.1039/c3ib40187a).
Spence started studying the storage of red blood cells about five years ago. His group had already been studying red blood cells for several years, but he had no experience in transfusion medicine. Then he was invited to serve on a National Institutes of Health study section on red blood cell storage for transfusion medicine. The experience opened his eyes.
Most surprising were the chemical conditions under which blood is stored. “Everyone kept talking about ‘the CPD,’ ” Spence says. “That’s the citrate, phosphate, dextrose—that is, glucose—solution that’s in the collection bag.”
A quick calculation revealed how high the glucose concentrations are. After the blood is added, the collection bag has a glucose concentration of about 20 mM. The red blood cells are transferred to another bag for storage, and the final glucose concentration in that bag is about 40 mM.
“I immediately started thinking these cells are in an environment that has way too much glucose,” Spence says. “Even the blood of type 1 diabetic rat models used for diabetes research doesn’t exceed the high teens millimolar glucose—and they have all sorts of complications.” Normal human blood glucose concentrations are 4 to 6 mM.
Spence and his students compared how cells fared in the standard storage solution and in one with approximately physiological glucose levels. They did this by using microfluidic systems that are designed to mimic blood vessels.
“When these cells are in the currently accepted storage solutions, they release less ATP, which in turn stimulates less nitric oxide,” Spence says. In solutions that contain normal physiological glucose levels, the ATP release is likewise close to normal.
And the effects of high glucose are almost immediate, Spence says. “We see reduced ATP and reduced nitric oxide after the red cells are collected and stored for 24 hours. Even after six hours we see differences.”
Over short times, the effect is reversible. Spence explains that if they store red blood cells in high glucose concentrations for a few days and then move some of them to buffer solutions with little or no glucose, the cells regain their ability to release ATP. But at times longer than two weeks, that reversibility vanishes.
Spence points out that in solutions that mimic physiologic conditions, the glucose runs out after seven to 10 days. To maintain physiological glucose levels, Wang periodically added a high-concentration glucose droplet. “But in practice you could never do that,” Spence says.
Spence’s findings suggest that it may be time to reconsider the solutions used to store red blood cells.
“The need for very high, nonphysiologic glucose concentrations is based on solid empirical data but rests in part on the assumption that one does not alter the composition of the stored product during the entire storage period,” says Brian R. Smith, a professor and the chair of laboratory medicine at Yale University. “Modern engineering advances have made it possible to envision cost-effective storage devices that could allow for more dynamic storage where metabolic waste products are removed and nutrients supplied in a more physiological range on a continuous basis.”
Michigan State hopes to do just that. The university has spun off a company called Life Blood to develop an improved glucose maintenance strategy for blood banking. Spence is serving in an advisory role, but he is not directly involved with the company.
Just don’t ask Spence if he’s trying to increase the shelf life of red blood cells beyond the current 42 days. That’s not the point. “Our goal,” he says, “is to reduce posttransfusion complications by giving you a better product on day 35 or on day two.”
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