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The FDA currently allows donated units of blood to be stored for 42 days. However, questions remain about whether older blood (within the 42-day limit) is harmful. Laboratory studies have shown that older blood has decreased levels of 2,3-diphosphoglycerate, decreased nitric oxide metabolism, impaired membrane deformability, and increased adherence to the endothelium, all of which theoretically decrease oxygen delivery to tissues. A retrospective study in cardiac surgery patients reported an association between older blood and increased mortality. However, several randomized trials in various patient populations, including pre-term infants and critically ill adults, have not.
In the Informing Fresh versus Old Red Cell Management (INFORM) Trial, published in this week’s NEJM, investigators performed the largest trial to date to assess the effects of the age of transfused blood on patient outcomes. In this study, 20,858 patients requiring blood transfusion in six hospitals across four countries from 2012 to 2015 were randomized to receive either the freshest available blood in the bank (median storage, 11 days) or the oldest blood in the bank (median storage, 23 days). Only patients with the most common blood types, types A and O, were included in the primary analysis because the increased availability of these donated blood units was expected to allow at least a 10-day mean difference between the oldest and freshest blood in the blood banks.
The primary outcome, in-hospital mortality, did not differ between patients who received the freshest blood and those who received the oldest blood (9.1% vs 8.7%, P=0.34). Furthermore, there were no significant mortality differences in three pre-specified high-risk subgroups including patients in the ICU, patients with cancer, and those undergoing cardiothoracic surgery. When these analyses were repeated by blood type, the results were similar.
In an accompanying editorial, Drs. Aaron Tobian and Paul Ness from the Division of Transfusion Medicine at Johns Hopkins University praise the study design for its large size, evaluating many more patients than all previous trials combined and thereby allowing a robust mortality analysis. They also highlight the pragmatic design of the INFORM trial, noting its potential “as a model for other trials” by using electronic data, waived consent, and an easily-assessed outcome (mortality), all of which markedly reduced cost. However, the editorialists caution, “Even though the results of the INFORM trial should end the debate regarding whether short-term or long-term storage of blood is advantageous, 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.”
The INFORM study answers important questions about outcomes for patients receiving blood transfusions of varying degrees of freshness using a pragmatic trial design. The large number and diversity of patients allows for greater generalizability, and further affirms previous studies that demonstrate no difference in mortality outcomes. John Jarcho, deputy editor at NEJM, noted, “This large trial should really settle the question of whether current storage policies are adequate to maintain the quality of the blood supply.”
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Wei Ko is a 4th year medical student at the University of Massachusetts Medical School