Angelo D'Alessandro1, Julie A Reisz1, Rachel Culp-Hill1, Herbert Korsten2, Robin van Bruggen3,4, Dirk de Korte2,3,4. 1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado. 2. Department of Product and Process Development, Sanquin Blood Bank, Amsterdam, the Netherlands. 3. Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands. 4. Landsteiner Laboratory, Academic Medical Centre, Amsterdam, the Netherlands.
Abstract
BACKGROUND: Over a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date. STUDY DESIGN AND METHODS: We performed UHPLC-MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E-SOL 5 and PAG3M for either 1, 21, 35 (end of shelf-life in the Netherlands), or 56 days. RESULTS: Alkaline additives (especially PAG3M) better preserved 2,3-diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such as hypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants. CONCLUSION: Alkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases.
BACKGROUND: Over a century of advancements in the field of additive solutions for red blood cell (RBC) storage has made transfusion therapy a safe and effective practice for millions of recipients worldwide. Still, storage in the blood bank results in the progressive accumulation of metabolic alterations, a phenomenon that is mitigated by storage in novel storage additives, such as alkaline additive solutions. While novel alkaline additive formulations have been proposed, no metabolomics characterization has been performed to date. STUDY DESIGN AND METHODS: We performed UHPLC-MS metabolomics analyses of red blood cells stored in SAGM (standard additive in Europe), (PAGGSM), or alkaline additives SOLX, E-SOL 5 and PAG3M for either 1, 21, 35 (end of shelf-life in the Netherlands), or 56 days. RESULTS: Alkaline additives (especially PAG3M) better preserved 2,3-diphosphoglycerate and adenosine triphosphate (ATP). Deaminated purines such ashypoxanthine were predictive of hemolysis and morphological alterations. Guanosine supplementation in PAGGSM and PAG3M fueled ATP generation by feeding into the nonoxidative pentose phosphate pathway via phosphoribolysis. Decreased urate to hypoxanthine ratios were observed in alkaline additives, suggestive of decreased generation of urate and hydrogen peroxide. Despite the many benefits observed in purine and redox metabolism, alkaline additives did not prevent accumulation of free fatty acids and oxidized byproducts, opening a window for future alkaline formulations including (lipophilic) antioxidants. CONCLUSION: Alkalinization via different strategies (replacement of chloride anions with either high bicarbonate, high citrate/phosphate, or membrane impermeant gluconate) results in different metabolic outcomes, which are superior to current canonical additives in all cases.
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Authors: Angelo D'Alessandro; Xiaoyun Fu; Julie A Reisz; Mars Stone; Steve Kleinman; James C Zimring; Michael Busch Journal: Transfusion Date: 2020-05-08 Impact factor: 3.157
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: Lorenzo Bertolone; Micaela Kalani Roy; Ariel M Hay; Evan J Morrison; Davide Stefanoni; Xiaoyun Fu; Tamir Kanias; Steve Kleinman; Larry J Dumont; Mars Stone; Travis Nemkov; Michael P Busch; James C Zimring; Angelo D'Alessandro Journal: Transfusion Date: 2020-04-27 Impact factor: 3.157