Older transfused blood as good as fresh (INFORM)
What's the shelf life of human blood? Like the milk in your fridge, stored donated human blood has an expiration date: currently it's 42 days, set by the FDA. But is fresher blood actually better? As with ordering wine by the glass, should patients about to be transfused blood ask for "whatever was opened most recently"? There's been reason to suspect this is the case. Older stored blood cells are less deformable (stiffer as they pass through tiny capillaries crammed together), are stickier inside blood vessels, and have lower levels of 2,3-diphosphoglycerate and nitric oxide metabolism. All of these factors could decrease oxygen delivery to tissues perfused by older transfused blood. Do any of those factors translate to a difference in clinical outcomes among people receiving older or fresher donated blood? At least 13 randomized trials (including some in critically ill adults and pre-term infants) and a big meta-analysis have said no. But these trials left an ooze of uncertainty, as did a retrospective study associating transfusion of older blood with increased mortality in people undergoing heart surgery. Given the public health implications of the question, it was time for a definite answer. It was time for the Canadians.
What They Did
The INFORM trial published in the New England Journal of Medicine provides the most robust data on the age-of-blood question to date. Investigators randomized 20,858 patients in Canada requiring transfusion of red blood cells to receive the freshest blood (~11 days old) or the oldest blood (~23 days old) in the hospital's blood bank. To avoid confounding by availability of blood, only people with A and O blood types (the most common) were enrolled.
What They Found
There was no difference in hospital mortality (the primary outcome) between groups: 9.1% among those receiving the freshest blood; 8.7% among those receiving the oldest blood (p=0.34). There were also no differences in mortality among patients with cancer, critical illness, or undergoing cardiothoracic surgery (pre-specified high risk subgroups).
What It Means
The age of available blood has long been an interesting medical-logistical problem with unresolved theoretical ethical implications. Generally speaking, in the U.S. the Red Cross sends the oldest blood to health centers with the highest transfusion volumes, where it will be more likely to be used. If older blood were poorer quality, it would mean these trauma and cardiothoracic surgery centers were short-changing their patients just so rural hospitals could have fresh blood that would often age out on the shelves. INFORM should put that question to rest, and validates the current practices employed in the U.S. by the Red Cross to ensure an efficient, safe, adequate national supply of safe blood. (Canada's blood supply is managed by the Canadian Blood Services, but the same principle holds.) However, the editorialists worry that blood in its final week of shelf life may yet prove to be inferior to fresher blood:
The question is still open as to whether the transfusion of red cells during the last week of storage (35 to 42 days) poses more risk than the transfusion of blood stored for shorter intervals.
Historically viewed by physicians as a panacea, it turns out blood transfusion is sometimes harmful. INFORM reassures us that donated blood in a wide middle range of ages appears indistinguishable, safety-wise. But the best way for intensivists to avoid worrying about the effects of the age of blood is to avoid transfusing at all, except when it's truly needed. Read more: Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion. N Engl J Med 2016; 375:1937-1945. [PubMed]