Angelo DʼAlessandro1,2, Tatsuro Yoshida3, Shawnagay Nestheide4, Travis Nemkov1, Sarah Stocker4, Davide Stefanoni1, Fatima Mohmoud4, Neeta Rugg4, Andrew Dunham3, Jose A Cancelas4,5. 1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado. 2. Department of Medicine - Division of Hematology, University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado. 3. Hemanext Inc, Lexington, Massachusetts. 4. Hoxworth Blood Center, University of Cincinnati Academic Health Center, Cincinnati, Ohio. 5. Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Abstract
BACKGROUND: Blood transfusion is a lifesaving intervention for millions of recipients worldwide every year. Storing blood makes this possible but also promotes a series of alterations to the metabolism of the stored erythrocyte. It is unclear whether the metabolic storage lesion is correlated with clinically relevant outcomes and whether strategies aimed at improving the metabolic quality of stored units, such as hypoxic storage, ultimately improve performance in the transfused recipient. STUDY DESIGN AND METHODS: Twelve healthy donor volunteers were recruited in a two-arm cross-sectional study, in which each subject donated 2 units to be stored under standard (normoxic) or hypoxic conditions (Hemanext technology). End-of-storage measurements of hemolysis and autologous posttransfusion recovery (PTR) were correlated to metabolomics measurements at Days 0, 21, and 42. RESULTS: Hypoxic red blood cells (RBCs) showed superior PTR and comparable hemolysis to donor-paired standard units. Hypoxic storage improved energy and redox metabolism (glycolysis and 2,3-diphosphoglycerate), improved glutathione and methionine homeostasis, decreased purine oxidation and membrane lipid remodeling (free fatty acid levels, unsaturation and hydroxylation, acyl-carnitines). Intra- and extracellular metabolites in these pathways (including some dietary purines) showed significant correlations with PTR and hemolysis, though the degree of correlation was influenced by sulfur dioxide (SO2 ) levels. CONCLUSION: Hypoxic storage improves energy and redox metabolism of stored RBCs, which results in improved posttransfusion recoveries in healthy autologous recipients-a Food and Drug Administration gold standard of stored blood quality. In addition, we identified candidate metabolic predictors of PTR for RBCs stored under standard and hypoxic conditions.
BACKGROUND: Blood transfusion is a lifesaving intervention for millions of recipients worldwide every year. Storing blood makes this possible but also promotes a series of alterations to the metabolism of the stored erythrocyte. It is unclear whether the metabolic storage lesion is correlated with clinically relevant outcomes and whether strategies aimed at improving the metabolic quality of stored units, such as hypoxic storage, ultimately improve performance in the transfused recipient. STUDY DESIGN AND METHODS: Twelve healthy donor volunteers were recruited in a two-arm cross-sectional study, in which each subject donated 2 units to be stored under standard (normoxic) or hypoxic conditions (Hemanext technology). End-of-storage measurements of hemolysis and autologous posttransfusion recovery (PTR) were correlated to metabolomics measurements at Days 0, 21, and 42. RESULTS: Hypoxic red blood cells (RBCs) showed superior PTR and comparable hemolysis to donor-paired standard units. Hypoxic storage improved energy and redox metabolism (glycolysis and 2,3-diphosphoglycerate), improved glutathione and methionine homeostasis, decreased purine oxidation and membrane lipid remodeling (free fatty acid levels, unsaturation and hydroxylation, acyl-carnitines). Intra- and extracellular metabolites in these pathways (including some dietary purines) showed significant correlations with PTR and hemolysis, though the degree of correlation was influenced by sulfur dioxide (SO2 ) levels. CONCLUSION: Hypoxic storage improves energy and redox metabolism of stored RBCs, which results in improved posttransfusion recoveries in healthy autologous recipients-a Food and Drug Administration gold standard of stored blood quality. In addition, we identified candidate metabolic predictors of PTR for RBCs stored under standard and hypoxic conditions.
Authors: Marion C Lanteri; Tamir Kanias; Sheila Keating; Mars Stone; Yuelong Guo; Grier P Page; Donald J Brambilla; Stacy M Endres-Dighe; Alan E Mast; Walter Bialkowski; Pam D'Andrea; Ritchard G Cable; Bryan R Spencer; Darrell J Triulzi; Edward L Murphy; Steven Kleinman; Mark T Gladwin; Michael P Busch Journal: Transfusion Date: 2018-11-08 Impact factor: 3.157
Authors: James T Yurkovich; Daniel C Zielinski; Laurence Yang; Giuseppe Paglia; Ottar Rolfsson; Ólafur E Sigurjónsson; Jared T Broddrick; Aarash Bordbar; Kristine Wichuk; Sigurður Brynjólfsson; Sirus Palsson; Sveinn Gudmundsson; Bernhard O Palsson Journal: J Biol Chem Date: 2017-10-13 Impact factor: 5.157
Authors: Julie A Reisz; Travis Nemkov; Monika Dzieciatkowska; Rachel Culp-Hill; Davide Stefanoni; Ryan C Hill; Tatsuro Yoshida; Andrew Dunham; Tamir Kanias; Larry J Dumont; Michael Busch; Elan Z Eisenmesser; James C Zimring; Kirk C Hansen; Angelo D'Alessandro Journal: Transfusion Date: 2018-10-12 Impact factor: 3.157
Authors: Katherine D Ellingson; Mathew R P Sapiano; Kathryn A Haass; Alexandra A Savinkina; Misha L Baker; Koo-Whang Chung; Richard A Henry; James J Berger; Matthew J Kuehnert; Sridhar V Basavaraju Journal: Transfusion Date: 2017-06 Impact factor: 3.157
Authors: Angelo D'Alessandro; Travis Nemkov; Kaiqi Sun; Hong Liu; Anren Song; Andrew A Monte; Andrew W Subudhi; Andrew T Lovering; Daniel Dvorkin; Colleen G Julian; Christopher G Kevil; Gopi K Kolluru; Sruti Shiva; Mark T Gladwin; Yang Xia; Kirk C Hansen; Robert C Roach Journal: J Proteome Res Date: 2016-09-27 Impact factor: 4.466
Authors: Elena Kozlova; Aleksandr Chernysh; Viktor Moroz; Aleksandr Kozlov; Viktoria Sergunova; Ekaterina Sherstyukova; Olga Gudkova Journal: Blood Transfus Date: 2020-12-17 Impact factor: 3.443
Authors: Angelo D'Alessandro; Xiaoyun Fu; Julie A Reisz; Tamir Kanias; Grier P Page; Mars Stone; Steve Kleinman; James C Zimring; Michael Busch Journal: Transfusion Date: 2020-05-11 Impact factor: 3.157
Authors: Tiffany Thomas; Francesca Cendali; Xiaoyun Fu; Fabia Gamboni; Evan J Morrison; Jonathan Beirne; Travis Nemkov; Marianna H Antonelou; Anastasios Kriebardis; Ian Welsby; Ariel Hay; Karolina H Dziewulska; Michael P Busch; Steven Kleinman; Paul W Buehler; Steven L Spitalnik; James C Zimring; Angelo D'Alessandro Journal: Transfusion Date: 2021-04-26 Impact factor: 3.337
Authors: Vassilis L Tzounakas; Alkmini T Anastasiadi; Marilena E Lekka; Effie G Papageorgiou; Konstantinos Stamoulis; Issidora S Papassideri; Anastasios G Kriebardis; Marianna H Antonelou Journal: Front Physiol Date: 2022-02-08 Impact factor: 4.566
Authors: Daniel Stephenson; Travis Nemkov; Syed M Qadri; William P Sheffield; Angelo D'Alessandro Journal: Front Physiol Date: 2022-02-07 Impact factor: 4.566
Authors: Lorenzo Bertolone; Hye Kyung H Shin; Jin Hyen Baek; Yamei Gao; Steven L Spitalnik; Paul W Buehler; Angelo D'Alessandro Journal: Front Physiol Date: 2022-03-21 Impact factor: 4.566