Assessing red blood cell product quality with 2,3-DPG, ATP and p50 assays: A BEST Collaborative study.

To comply with regulatory guidelines, blood products undergo laboratory testing to assess red blood cell (RBC) quality during manufacturing, storage and delivery. Measurements of metabolites such as 2,3-diphosphoglycerate (2,3-DPG) have been relied upon as proxies for in vivo function, although their predictive value for clinical efficacy is not well substantiated. Following the discontinuation of the only validated commercial assay for 2,3-DPG, we reviewed existing literature and performed a retrospective analysis of datasets from two blood centres in North America to evaluate adenosine-5'-triphosphate (ATP) and p50 as alternatives. The literature did not provide sufficient evidence to support adopting p50 in place of 2,3-DPG. Although the assays are complementary, we found several exceptions in which biological and technical factors reduced the strength of correlation between 2,3-DPG and p50. ATP, another marker of RBC quality, was not well correlated either with 2,3-DPG or p50 in quality monitoring datasets or with in vivo circulation kinetics in healthy adults. Our assessment underscores the need for a replacement assay for 2,3-DPG for comprehensive characterization of novel red cell products and storage conditions.