Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells

D’Alessandro, Angelo; Reisz, Julie A.; Culp‐Hill, Rachel; Korsten, Herbert; Bruggen, Robin van; Korte, Dirk de

doi:10.1111/trf.14620

Cited by 47 publications

(41 citation statements)

References 58 publications

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“…During the past decade, omics investigations of human RBC units stored using all currently licensed storage additives helped to identify the impact of processing strategies (including leukoreduction and storage solutions) and donor variability on the molecular heterogeneity of stored units. In the face of a growing body of evidence documenting the storage lesion, little is known about whether any of these metabolic changes that accumulate during storage in the blood bank ultimately impact RBC performance upon transfusion in vivo .…”

Section: Discussionmentioning

confidence: 99%

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

et al. 2020

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“…ATP was measured by mass spectrometry, as described . Metabolic measurements of ATP were performed via ultra‐high‐pressure liquid chromatography coupled to mass spectrometry (Vanquish–Q Exactive, Thermo Fisher), as described …”

Section: Methodsmentioning

confidence: 99%

Reexamination of the chromium‐51–labeled posttransfusion red blood cell recovery method

et al. 2019

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BACKGROUND: The chromium-51-labeled posttransfusion recovery (PTR) study has been the goldstandard test for assessing red blood cell (RBC) quality. Despite guiding RBC storage development for decades, it has several potential sources for error. METHODS: Four healthy adult volunteers each donatedan autologous, leukoreduced RBC unit, aliquots were radiolabeled with technetium-99m after 1 and 6 weeks of storage, and then infused. Subjects were imaged by single-photon-emission computed tomography immediately and 4 hours after infusion. Additionally, from subjects described in a previously published study, adenosine triphosphate levels in transfusates infused into 52 healthy volunteers randomized to a single autologous, leukoreduced, RBC transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage were correlated with PTR and laboratory parameters of hemolysis.RESULTS: Evidence from one subject imaged after infusion of technetium-99m-labeled RBCs suggests that, in some individuals, RBCs may be temporarily sequestered in the liver and spleen immediately following transfusion and then subsequently released back into circulation; this could be one source of error leading to PTR results that may not accurately predict the true quantity of RBCs cleared by intra-and/or extravascular hemolysis. Indeed, adenosine triphosphate levels in the transfusates correlated more robustly with measures of extravascular hemolysis in vivo (e.g., serum iron, indirect bilirubin, non-transferrin-bound iron) than with PTR results or measures of intravascular hemolysis (e.g., plasma free hemoglobin).CONCLUSIONS: Sources of measurement error are inherent in the chromium-51 PTR method. Transfusion of an entire unlabeled RBC unit, followed by quantifying extravascular hemolysis markers, may more accurately measure true posttransfusion RBC recovery. T he chromium-51-labeled posttransfusion recovery (PTR) method is currently the gold-standard test for assessing the quality of stored red blood cells (RBCs) for transfusion. 1 As per the US Food and ABBREVIATIONS: AUC = area under the curve; FDA = US Food and Drug Administration; PTR = posttransfusion recovery; SPECT = single-photon-emission computed tomography; VOIs = volumes of interest. From the

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“…However, as RBCs are stored in the blood bank, they accumulate a series of biochemical and morphological alterations, collectively referred to as the storage lesion . The stored RBCs are challenged by low storage temperatures, incubation with nonbiological media (i.e., storage additives), and exposure to (mM levels of) plasticizers, all factors impacting the energy and redox balance of the stored RBCs and, ultimately, their morphology, stiffness, and hemolytic propensity in vitro and, upon transfusion, in vivo . However, reassuring evidence from randomized clinical trials mitigated most of the concerns related to the age of blood (reviewed in Belpulsi and colleagues).…”

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Effects of red blood cell (RBC) transfusion on sickle cell disease recipient plasma and RBC metabolism

et al. 2018

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Background Exchange transfusion is a mainstay in the treatment of sickle cell anemia. Sickle cell recipients can be transfused over 10 units per therapy, an intervention that replaces circulating sickle red blood cells (RBCs) with donor RBCs. Storage of RBCs makes the intervention logistically feasible. The average storage duration for units transfused at the Duke University Medical Center is ~two weeks, a time window that should anticipate the accumulation of irreversible storage lesion to the erythrocyte. However, no metabolomics study has been performed to date to investigate the impact of exchange transfusion on recipients’ plasma and red blood cell phenotypes. Study design and Methods Plasma and red blood cells were collected from sickle cell patients before transfusion and within 5h from exchange transfusion with up to 11 units, prior to metabolomics analyses. Results Exchange transfusion significantly decreased plasma levels of markers of systemic hypoxemia like lactate, succinate, sphingosine 1-phosphate and 2-hydroxyglutarate. These metabolites accumulated in transfused RBCs, suggesting that RBCs may act as scavenger/reservoirs. Transfused RBCs displayed higher glycolysis, total adenylate pools and DPG, consistent with increased capacity to deliver oxygen. Plasma levels of acyl-carnitines and amino acids decreased, while fatty acids and potentially harmful phthalates increased upon exchange transfusion. Conclusion Metabolic phenotypes confirm the benefits of the transfusion therapy in sickle cell recipients and the reversibility of some of the metabolic storage lesion upon transfusion in vivo in two-week-old RBCs. However, results also suggest that potentially harmful plasticizers are transfused.

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Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells

Abstract: 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.

Cited by 47 publications

References 58 publications

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

Reexamination of the chromium‐51–labeled posttransfusion red blood cell recovery method

Effects of red blood cell (RBC) transfusion on sickle cell disease recipient plasma and RBC metabolism

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