Publications & Presentations

Check out Evolving RBC-omics from cross-sectional to longitudinal study as published in October 2025's Transfusion Today magazine.

The Recipient Epidemiology and Donor Evaluation Study (REDS)-III RBC-Omics Study enrolled ~14,000 whole blood donors in 2010-2012 with prospective characterization of RBC storage, oxidative and osmotic hemolysis.

DNA was recovered from leukoreduction filters from RBC-Omics whole blood donations, which enabled execution of a genome wide association study (GWAS) using a customized transfusion medicine array (TM Array) that identified 27 GWAS-level significant genetic loci associated with in vitro measures of hemolysis following blood storage, most of which express functional RBC intracellular and membrane proteins; 7 of these loci were also identified as associated with in vivo hemolysis in sickle cell disease patients. During the subsequent and currently active REDS-IV-P program further analyses have been and continue to be executed that have provided extensive additional findings on donor, component, and recipient characteristics and genetic, metabolomic and other omics findings that impact RBC function, storage capacity and transfusion efficacy, which was ascertained by deriving pre-/post-transfusion hemoglobin increments and changes in bilirubin in a vein-to-vein (V2V) database generated during the corresponding REDS-III program.

Many additional genetic loci that correlate with in vitro RBC function and in vivo RBC recovery and survival were identified by integrating metabolomic, proteomic and GWAS data through quantitative trait loci analyses (mQTL and pQTL). Perturbations of RBCs during storage, such as energy depletion, lipid peroxidation, failure to mitigate oxidative stress, and mutations impacting expression and function of enzymes such as glucose phosphate dehydrogenase (GSPD), contribute to suboptimal storage quality and impaired transfusion efficacy (reviewed in reference 1 which provides citations to key RBC-Omics publications). Moreover, the REDS RBC-Omics group has advanced the concept of the blood donor exposome, highlighting how donor exposures −including many not subject to current deferral criteria such as caffeine consumption− may influence storage outcomes as much as, or more than, storage duration2.

We recently realized that the scientific contributions from the original RBC-Omics research program executed during REDS-III and subsequent omics studies using the RBC-Omics repository and linked V2V database during REDS-IV-P, could be significantly advanced by linking the RBC-Omics donors and genetic and metabolomic data to the current donation status/ and recent donation histories of the RBC-Omics donors at the blood collection organizations represented by the four REDS-III RBC-Omics hubs.

We can also determine which RBC-Omics donors were included in two recent independent studies supported by the Centers Disease Control and Prevention (CDC): the SARS-CoV-2 Repeat Donor Cohort (RDC) conducted from 2020-2023 and the recently launched and ongoing Respiratory Virus Repeat Donor Cohort (RV-RDC) launched in 2025. Such linkage will enable access to both respiratory virus infection incidence and outcomes and to donation-derived repository samples, including longitudinal plasma samples derived from 2020-2023 donation and whole blood. pRBC, buffy coat (BC) and plasma preparations from RDC donors in 2023. This will allow for analyses of a compiled database of recent donation patterns of RBC-Omics donors to gain insights into correlates of donor longevity, as well as access to data and samples from the 2023RDC repository to perform omics testing on samples collected 10-15 years after the original study period.

We verified that each of the original four REDS-III hubs where RBC-Omics donors were enrolled can link coded study IDs with current donor IDs, and that ~25% of the RBC-Omics donors (~4000 donors) are still active donors who donated multiple times over the past several years. Furthermore, approximately 20% of the RBC-Omics donors at ARC and Vitalant also participated in the RDC program from 2020-2023 and 15% are currently enrolled in the RV-RDC program. We are now in the process of developing a consolidated database that links RBC-Omics donor IDs and the comprehensive database to recent donation histories and to the REDS-IV-P V2V database with donor, component and recipient data from 2019 through 2024. This will allow us to conduct a “donation longevity GWAS” based on TM-Array and m/p-QTL genetic results to identify potential genetic predictors of capacity for sustained donations (genetic correlates of the healthy donor effect). We will also be able to conduct transfusion outcomes analyses based on the REDS-IVP V2V database to determine if our previously reported relationships between RBC-Omics GWAS and metabolomics findings impacting transfusion efficacy were maintained over greater than a decade of donations and transfusions.

On a separate track, by linking RBC-Omics donors to 2023RDC and RV-RDC participants and samples, we will be able to perform GWAS analysis of SARS-COV-2 and other RV infection outcomes. We plan to access archived longitudinal plasma samples from 2020-2023 and WB, RBC, BC and plasma samples from Q3/Q4 2023 for and conduct similar Omics analyses to characterize the stability of Omics findings from donations given over a decade apart, and to investigate the relationships between Omics results derived from plasma, RBC and whole blood sample. Finally, we are developing a new protocol to survey both still donating and lapsed RBC-Omics donors to establish a blood donor-based health outcomes cohort.

We believe that this approach of refreshing a large laboratory and epidemiological study of blood donors and recipients initiated almost 15 years ago, by linking donors and data from that study to recent donation histories, other repeat donor cohorts and health outcomes surveys, provides a novel approach that can be pursued by other investigators in the ISBT Big Data Working Party.

References

1. Assessing RBC transfusion efficacy in chronic transfusion recipients: advancing precision transfusion medicine. Norris PJ, Busch MP. Blood Transfus. 2025; 23(5): 385-388
2. Caffeine impairs red blood cell storage quality by dual inhibition of ADORA2b signaling and G6PD activity. Dzieciatkowska M, Hay A, Issaian A, Keele GR, Bevers S, Nemkov T, Reisz JA, Maslanka M, Stephenson D, Moore AL, Deng X, Stone M, Hansen KC, Kleinman S, Norris PJ, Busch MP, Page GP, Roubinian N, Xia Y, Zimring JC, D'Alessandro A. Haematologica. 2025 Sep 4. doi: 10.3324/haematol.2025.288332. PMID: 40905089