Professor University of Colorado Anschutz Medical Campus Aurora, Colorado, United States
Background/Case Studies: Transfusion of packed red blood cells (RBCs) is life-saving intervention for millions of recipients every year worldwide. RBCs transfusion is the most common in hospital medical procedure after vaccination, making RBC units one of the most common biotherapeutics in the world. Yet, one of the ongoing challenges in the field remains the standardization of the dose and purity of transfusion products as a drug. As such, the question “what’s in a blood bag?” remains one of the outstanding priorities identified by the National Heart, Lung, and Blood Institutes-sponsored “State of Science in Transfusion Medicine” in 2022.
Study
Design/Methods: We investigated the molecular composition of blood products from 13,091 donor volunteers enrolled in four different blood centers across the United States as part of the Recipient Epidemiology and Donor Evaluation Study – REDS RBC Omics (henceforth referred to as “index” donation). To perform such a large scale study, we developed a novel ultra-high throughput metabolomics method to process packed RBC samples with analytical time of ~1 minute/sample.
Results/Findings: In addition to identifying over 200 endogenous metabolites, we detected and relatively quantified over 200 xenometabolites including dietary substances (e.g., caffeine, resveratrol, markers of alcohol consumption), xenobiotics (drugs that are not grounds for blood donor deferral) or other exposures (e.g., habits, such as cotinine for smoking or other nicotine exposures). Our data confirm earlier smaller scale reports on the so-called “blood donor exposome" and expand our knowledge of the molecular complexity of packed RBC product, identifying caffeine and acetaminophen as the most common dietary or drug-derived small molecules in blood products. Some metabolites were associated with altered in vitro hemolytic propensity, for example with beneficial effects of some metabolites of dietary origin, such as the antioxidant ergothioneine. Conclusions: Packed RBC products contain traces of small molecule metabolites of exposures. Detailed mechanistic and clinical studies will be necessary to evaluate the impact, if any – given the trace amounts detected for most of these metabolites – on storage quality and transfusion safety and efficacy.
Importance of research: Characterization of the molecular composition of blood product remains an ongoing challenge towards the standardization of safety and efficacy of RBC units designated for transfusion. Here we report the identification of hundreds of metabolites of dietary or other exposure from over 13,000 packed red blood cell samples from the REDS RBC Omics study.
