Fresh versus old blood: are there differences and do they matter?

The medical effects of transfusing stored RBCs is an area of significant concern that has received substantial attention in recent years. Retrospective trials show all possible outcomes, including sequelae from transfusing older RBCs, no difference between older and fresher RBCs, and a benefit to older RBCs. Several prospective clinical trials are under way to further investigate potential untoward effects of stored RBCs. Thus far, the issue of potential sequelae from transfusing stored RBCs remains a highly controversial issue. However, what is not controversial is that RBC storage is an unnatural state during which a series of substantial changes take place to the stored RBCs. These changes result in the formation of cellular and chemical entities known to have biological activities in other settings, giving rise to several distinct hypotheses by which stored RBCs may alter recipient biology. Herein, the clinical background and basic science of RBC storage are reviewed, with a particular focus on factors that may complicate hypothesis testing and obfuscate underlying biologies. The complexity of the RBC storage lesion, donor-to-donor variation, and the diversity of recipient pathophysiologies remain a challenge to prospective trials assessing the safety of stored RBCs.