November 29, 2008
For optimal health, fresh food, water and air are the best choices. Now experts are considering whether the same advice about freshness should also apply to blood.
The U.S. Food and Drug Administration allows blood to be used for up to six weeks after it’s collected. However, a study published earlier this year in the New England Journal of Medicine raised questions about safety issues pertaining to the use of older blood and the standards surrounding blood storage.
The study, conducted at The Cleveland Clinic, found that heart surgery patients who received blood that was more than two weeks old were more likely to suffer potentially serious post-operative complications.
And just last month, researchers presented the results of another study conducted at Cooper University Hospital in Camden, N.J. They found that intensive-care unit patients transfused with blood that had been stored for 29 days had a greater chance of infection—including pneumonia, urinary tract or other life-threatening infections—than when given blood stored for 28 days or less.
What do these findings portend for the nation’s blood supply?
“People should not be worried about receiving needed transfusions of blood stored up to 42 days,” says Darrell Triulzi, M.D., who runs the division of transfusion medicine at the University of Pittsburgh and is on the board of directors of AABB (formerly known as the American Association of Blood Banks).
The FDA’s six-week time frame—which is based on clinical studies that demonstrated at least a 75 percent recovery of red blood cells in the circulation after being infused into human volunteers—has been in effect for close to 30 years, says Jaroslav Vostal, M.D. Ph.D., head of the laboratory of cellular hematology at the FDA’s Center for Biologics Evaluation and Research. Vostal points out that the FDA approves all devices related to the collection and storage of blood.
“Blood products are very safe products,” says Basil Golding, M.D., acting associate director for medical affairs, also at the FDA’s Center for Biologics Evaluation and Research. “There are around eight million transfusions a year in the U.S., and the number of related fatalities (about 75 a year) is relatively small.”
So, if blood up to six weeks old is safe to use, how come recent research suggests otherwise?
Don’t jump to conclusions about older blood compared to newer, suggests Triulzi, who believes it’s important to understand the design of much of the recent research. Both the Cleveland Clinic and Cooper University Hospital studies were retrospective studies.
With retrospective studies, you’re looking at data that already exists, explains Triulzi. There’s no way to control for many variables—such as how much blood is transfused, the age of the patient, or the disease being treated—that may have affected the outcome. He points out that in the Cleveland Clinic study, more patients with severe heart dysfunction had received the older blood. “Those patients were already more likely to have a worse outcome,” he says.
However, not all experts agree with Triulzi’s opinion.”Some retrospective studies can result in relatively strong and substantial conclusions,” argues David Gerber, D.O., lead researcher on the Cooper University Hospital study and associate director of that hospital’s medical-surgical intensive care unit.
“If there is information coming out of a retrospective study that’s provocative, there’s impetus to proceed with prospective randomized studies in that same area,” says Gerber. With a randomized study, he says, patient data is collected in the moment, and it’s not known in advance which patient will get which treatment (or, in this case, how old blood is the blood received). “Randomized prospective studies remain the gold standard,” says Gerber.
Many experts agree with Gerber. The AABB, American Red Cross and America’s Blood Centers all state that more randomized prospective clinical trials are needed to determine whether the age of transfused blood influences outcomes.
“The issues of red [blood] cell quality and safety have been around for a long time, and the recent studies raise awareness that there could be an issue with older blood,” says Vostal. Triulzi believes current storage policy would not be changed “unless there was compelling data to document it was important to do so.”
“We do not suggest a change in FDA policy based on our study findings,” says Colleen Gorman Koch, M.D., the lead researcher on the Cleveland Clinic study, and the vice chair of research and education in that hospital’s cardiothoracic anesthesiology department.
But Koch is also in favor of additional research to closely examine the impact of blood storage duration and outcomes in cardiac surgery. To this end, the Cleveland Clinic has already begun a two-year randomized prospective study to examine this issue.
The National Institutes of Health will also sponsor a randomized prospective trial to study the impact of length of blood storage time on cardiac surgical patients. Triulzi, who’s one of the study’s co-investigators, says this multi-centered clinical trial is expected to begin enrollment in 2009 and will continue over a four-year period. The study hopes to include about 1,400 patients.
Of course, experts are highly aware that, should future studies prove that fresher blood is indeed safer to use, any change in FDA policy would affect the U.S. blood supply. For now, newborns get priority for the freshest blood, and, Triulzi said, if further studies support the theory that fresher blood is safer, then cardiac patients are likely be next in line to receive the most recent donations.
Just like food displayed in a supermarket, blood banks tend to use older blood first. But if the FDA decreased the time limit on storage, the supplies (which are often dangerously low to start with,especially around the holidays) would probably dwindle fast.
“We have to weigh the implications of decreasing storage time,” says Gerber. “Any decrease in the blood supply could have unintended consequences, if there’s a sudden demand or if there aren’t enough donors.”
And, says Vostal, shortening the storage time would probably affect the way blood banks operate. “I’m sure there’d be a major push to recruit more donors,” he says. “You’d need more people donating more blood more often.”
If future research indisputably showed that fresher blood was safer, Triulzi believes the new data “would create an impetus to improve the quality of stored blood, potentially by finding better preservatives.” Triulzi says that these types of formulations have already been developed on an experimental basis, but they haven’t yet been submitted for FDA approval “because there hasn’t been a great demand for them.”
No matter how advanced the research is down the line, the workings of blood might still remain a mystery. Says Triulzi: “If older blood is worse, we still don’t know why it’s worse.” Coeli Carr