Unsettling new evidence suggests that blood stored for more than 2 weeks might be less beneficial to recipients recovering from cardiac surgery than is fresher blood. While the study falls short of heralding a wholesale change in blood-banking practices, scientists agree that it exposes the need for a large trial to determine the optimal shelf life of stored blood. The current limit is 42 days.

Laboratory research has indicated that stored blood loses quality over time (SN: 10/27/07, p. 269). But previous studies of patients who received old or new blood proved inconclusive.

"No one expects blood to get a lot better during storage. It's not vintage port," says Harvey Klein, a hematologist who heads the Department of Transfusion Medicine at the National Institutes of Health in Bethesda, Md. It may be possible to show that blood cells get "run down" over time, he says, "but it's much more difficult to demonstrate that that's harmful to patients."

In the new study, researchers at the Cleveland Clinic Foundation analyzed the records of 6,002 people, average age 70, who received transfusions of red blood cells between 1998 and 2006. All were getting either heart bypass or valve surgery, or both.

Follow-up patient records revealed that those receiving blood more than 2 weeks old were more likely to have kidney failure, to need a ventilator for more than 3 days to breathe, to develop a blood disorder called sepsis, or to die within a year—compared with those getting fresher blood. The researchers excluded patients who got a mixture of newer and older blood. The report appears in the March 20 New England Journal of Medicine.

"This is an amazing study," says Timothy McMahon, a physician and pharmacologist at Duke University in Durham, N.C. "It's very robust and methodologically sound."

But McMahon cautions that the issue isn't settled. Scientists need to replicate these findings in a large trial that tracks patients of comparable health over months or years. Researchers would randomly assign patients to get new or older blood with neither patients nor doctors aware of which participants received the fresher blood.

Meanwhile, scientists have noticed changes in stored red blood cells that might explain the purported shortcomings of the older blood cells.

"They form long chains, like miniature doughnuts stacked on one another," says study coauthor Eugene Blackstone, a physician at the Cleveland Clinic. That makes it harder for the cells to fit through capillaries.

Stored red blood cells also lose some of their ability to alter their shape readily, McMahon says. "Often, a 6- or 8-micron red blood cell is asked to get through a 3-micron capillary," he says. "It needs to be supple to flow through properly. If a few red blood cells cannot do that, they obstruct the vessel."

Red blood cells deliver oxygen to tissues. But stored blood loses a chemical called 2,3-DPG (for 2,3 diphosphoglycerate) that facilitates the unloading of oxygen from hemoglobin molecules on red blood cells. While the cells begin to replenish supplies of 2,3-DPG after a transfusion, concentrations don't immediately reach the original levels, notes study co-author Colleen Koch, an anesthesiologist at the Cleveland Clinic.

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