Choosing the oldest rather than the freshest red cells in the blood bank does not jeopardise safety, according to a new trial in more than 20,000 patients.

The INFORM study randomised general hospital patients requiring a transfusion to available red cells that had been stored for either the shortest duration (mean 13.0 days) or the longest duration (23.6 days).

Six hospital participated. There were three in Canada, one in the United States, one in Israel, and the Flinders Medical Centre in Adelaide which contributed 4,989 cases (24% of the total).

In-hospital mortality was similar in both groups, amounting to 9.1% in the short-term storage group and 8.7% in the long-term storage group (p=0.34). “The results were consistent in three prespecified high-risk subgroups: patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer,” the researchers said.

An editorial noted the long-standing controversy about the health of older red cells. A ‘storage lesion’ was thought to include lower 2,3 diphosphoglycerate levels, reduced nitric oxide metabolism, impaired deformability and increased endothelial adherence.

The controversy persisted despite the fact that none of 13 randomised trials over the last 20 years showed that fresher cells were superior. One exception was a retrospective study in 2008 suggesting older cells were associated with higher mortality in patients after cardiac surgery.

Strengths of the INFORM study included its very large size, enrolling almost four times the number of patients included in all previous trials combined, and the inclusion of general hospital populations rather than selected high-risk subgroups.

The editorial also praised INFORM’s pragmatic design. “The investigators were able to enrol and randomly assign more than 30,000 patients in approximately 3 years at an approximate cost of $40 per patient by using electronic databases, consent waivers (because all the patients received treatment that was consistent with the current standard of care), and objective outcomes, including mortality rather than the surrogate markers that were used in smaller trials,” it said.

While the study should end the debate about possible harms of long-term red cell storage, there was still some uncertainty about the quality of cells during the last week of their approved 42-day life span in the blood bank, it said.