Angelo D'Alessandro1, Travis Nemkov1, Marguerite Kelher2, F Bernadette West3, Rani K Schwindt1, Anirban Banerjee4,5, Ernest E Moore4,5, Christopher C Silliman4,6,2, Kirk C Hansen1. 1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado. 2. Research Laboratory, Bonfils Blood Center, Denver, Colorado. 3. Clinical Services, Bonfils Blood Center, Denver, Colorado. 4. Department of Surgery, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado. 5. Denver Health Medical Center, Denver, Colorado. 6. Department of Pediatrics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado.
Abstract
BACKGROUND: In most countries, red blood cells (RBCs) can be stored up to 42 days before transfusion. However, observational studies have suggested that storage duration might be associated with increased morbidity and mortality. While clinical trials are under way, impaired metabolism has been documented in RBCs stored in several additive solutions (ASs). Here we hypothesize that, despite reported beneficial effects, storage in AS-3 results in metabolic impairment weeks before the end of the unit shelf life. STUDY DESIGN AND METHODS: Five leukofiltered AS-3 RBC units were sampled before, during, and after leukoreduction Day 0 and then assayed on a weekly basis from storage Day 1 through Day 42. RBC extracts and supernatants were assayed using a ultra-high-performance liquid chromatography separations coupled online with mass spectrometry detection metabolomics workflow. RESULTS: Blood bank storage significantly affects metabolic profiles of RBC extracts and supernatants by Day 14. In addition to energy and redox metabolism impairment, intra- and extracellular accumulation of amino acids was observed proportionally to storage duration, suggesting a role for glutamine and serine metabolism in aging RBCs. CONCLUSION: Metabolomics of stored RBCs could drive the introduction of alternative ASs to address some of the storage-dependent metabolic lesions herein reported, thereby increasing the quality of transfused RBCs and minimizing potential links to patient morbidity.
BACKGROUND: In most countries, red blood cells (RBCs) can be stored up to 42 days before transfusion. However, observational studies have suggested that storage duration might be associated with increased morbidity and mortality. While clinical trials are under way, impaired metabolism has been documented in RBCs stored in several additive solutions (ASs). Here we hypothesize that, despite reported beneficial effects, storage in AS-3 results in metabolic impairment weeks before the end of the unit shelf life. STUDY DESIGN AND METHODS: Five leukofiltered AS-3RBC units were sampled before, during, and after leukoreduction Day 0 and then assayed on a weekly basis from storage Day 1 through Day 42. RBC extracts and supernatants were assayed using a ultra-high-performance liquid chromatography separations coupled online with mass spectrometry detection metabolomics workflow. RESULTS: Blood bank storage significantly affects metabolic profiles of RBC extracts and supernatants by Day 14. In addition to energy and redox metabolism impairment, intra- and extracellular accumulation of amino acids was observed proportionally to storage duration, suggesting a role for glutamine and serine metabolism in aging RBCs. CONCLUSION: Metabolomics of stored RBCs could drive the introduction of alternative ASs to address some of the storage-dependent metabolic lesions herein reported, thereby increasing the quality of transfused RBCs and minimizing potential links to patient morbidity.
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