Osmotic hemolysis is a donor‐specific feature of red blood cells under various storage conditions and genetic backgrounds

Tzounakas, Vassilis L.; Anastasiadi, Alkmini T.; Valsami, Serena; Stamoulis, Konstantinos; Papageorgiou, Effie; Politou, Marianna; Papassideri, Issidora S.; Kriebardis, Anastasios G.; Antonelou, Marianna H.

doi:10.1111/trf.16558

Cited by 19 publications

(30 citation statements)

References 27 publications

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“…Genome-wide association studies (GWAS) identified several loci associated with hemolysis (Page et al, 2021;Fang et al, 2022) or metabolism (Moore et al, 2022) of stored RBCs, and similar conclusions also arose from classic twin studies (van 't Erve et al, 2014a;van 't Erve et al, 2014b). Correlation analyses support these findings (Reisz et al, 2017;Tzounakas et al, 2021), and enrich them with inter-correlations, namely, correlations between distinct parameters, either before/during storage, or between different time points of storage (D'Alessandro et al, 2021;Thomas et al, 2021;Anastasiadi et al, 2022). Such information has the potential to indicate or hint at how variation in one parameter might affect another, and therefore, lead to a better understanding of the "dialogue" between discrete aspects of RBC life during storage.…”

Section: Introductionmentioning

confidence: 77%

“…The maintenance of proportional storage, osmotic and mechanical hemolysis levels, among all time points in every condition tested, suggests that hemolysis is more a function of donor features than of additive solution modifications. According to previous studies, the osmotic fragility of stored RBCs is strongly donor-dependent since it varies proportionally to the circulation levels ( Tzounakas et al, 2021 ), being moderately associated with genes implicated in RBC structure and volume ( Page et al, 2021 ). The undeniable contribution of structural proteins and ion channels to mechanical fragility ( Smith et al, 2018 ; Svetina et al, 2019 ), leads to the assumption that there is a corresponding donor effect.…”

Section: Discussionmentioning

confidence: 99%

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The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

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Oxidative phenomena are considered to lie at the root of the accelerated senescence observed in red blood cells (RBCs) stored under standard blood bank conditions. It was recently shown that the addition of uric (UA) and/or ascorbic acid (AA) to the preservative medium beneficially impacts the storability features of RBCs related to the handling of pro-oxidant triggers. This study constitutes the next step, aiming to examine the links between hemolysis, redox, and metabolic parameters in control and supplemented RBC units of different storage times. For this purpose, a paired correlation analysis of physiological and metabolism parameters was performed between early, middle, and late storage in each subgroup. Strong and repeated correlations were observed throughout storage in most hemolysis parameters, as well as in reactive oxygen species (ROS) and lipid peroxidation, suggesting that these features constitute donor-signatures, unaffected by the diverse storage solutions. Moreover, during storage, a general “dialogue” was observed between parameters of the same category (e.g., cell fragilities and hemolysis or lipid peroxidation and ROS), highlighting their interdependence. In all groups, extracellular antioxidant capacity, proteasomal activity, and glutathione precursors of preceding time points anticorrelated with oxidative stress lesions of upcoming ones. In the case of supplemented units, factors responsible for glutathione synthesis varied proportionally to the levels of glutathione itself. The current findings support that UA and AA addition reroutes the metabolism to induce glutathione production, and additionally provide mechanistic insight and footing to examine novel storage optimization strategies.

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Section: Introductionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Anastasiadi

Stamoulis²,

Papageorgiou

et al. 2023

Front. Aging

Self Cite

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“…29 Intriguingly, when HOD and KEL are expressed on the same cell the impact of antigenspecific storage outcomes was preserved, strongly suggesting that even with mixed sex donor RBCs, storage can differentially impact alloimmunization. However, strainspecific modifications of storage in addition to donor sex, which can likewise impact RBC storage, 19,30 may also impact antigen-specific storage outcomes. Despite these limitations, the ability of this system to model key features of RBC alloimmunization provides important insight into general principles of RBC storage that may shape the likelihood of alloimmunization.…”

Section: Resultsmentioning

confidence: 99%

Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice

et al. 2023

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Introduction The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC‐induced alloantibody production and others failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens. Methods RBCs expressing two distinct model antigens, HEL‐OVA‐Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion. Transfused donor RBC survival was assessed within 24 h of transfusion, while IgM and IgG antibody production were assessed 5 and 14 days after transfusion. Results Stored HOD or KEL RBCs retained similar HEL or KEL antigen levels, respectively, as fresh RBCs, but did exhibit enhanced RBC clearance with increased storage age. Storage enhanced IgG antibody formation against HOD, while the oppositive outcome occurred following transfusion of stored KEL RBCs. The distinct impact of storage on HOD or KEL alloimmunization did not appear to reflect intrinsic differences between HOD or KEL RBCs, as transfusion of stored HOD × KEL RBCs resulted in increased IgG anti‐HOD antibody development and reduced IgG anti‐KEL antibody formation. Conclusions These data demonstrate a dichotomous impact of storage on immunization to distinct RBC antigens, offering a possible explanation for inconsistent clinical experience and the need for additional studies on the relationship between RBC storage and alloimmunization.

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“…Furthermore, menopause seems to promote membrane remodeling of red cells, especially during prolonged storage [59]. Furthermore, osmotic fragility, an aspect that is very important for hemolysis during storage and after transfusion of stored blood, appears correlated with donor sex [81]. So far, comparable data for the impact of donor sex on the storage lesion in large animal red blood cells are poor.…”

Section: Discussionmentioning

confidence: 99%

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates—A Scoping Review of The Literature

2022

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Background and Objectives: Transfusion of red cell concentrates is a key component of medical therapy. To investigate the complex transfusion-associated biochemical and physiological processes as well as potential risks for human recipients, animal models are of particular importance. This scoping review summarizes existing large animal transfusion models for their ability to model the physiology associated with the storage of erythrocyte concentrates. Materials and Methods: The electronic databases PubMed, EMBASE, and Web of Science were systematically searched for original studies providing information on the intravenous application of erythrocyte concentrates in porcine, ovine, and canine animal models. Results: A total of 36 studies were included in the analysis. The majority of porcine studies evaluated hemorrhagic shock conditions. Pig models showed high physiological similarities with regard to red cell physiology during early storage. Ovine and canine studies were found to model typical aspects of human red cell storage at 42 days. Only four studies provided data on 24 h in vivo survival of red cells. Conclusions: While ovine and canine models can mimic typical human erythrocyte storage for up to 42 days, porcine models stand out for reliably simulating double-hit pathologies such as hemorrhagic shock. Large animal models remain an important area of translational research since they have an impact on testing new pharmacological or biophysical interventions to attenuate storage-related adverse effects and allow, in a controlled environment, to study background and interventions in dynamic and severe disease conditions.

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Osmotic hemolysis is a donor‐specific feature of red blood cells under various storage conditions and genetic backgrounds

Cited by 19 publications

References 27 publications

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

The time-course linkage between hemolysis, redox, and metabolic parameters during red blood cell storage with or without uric acid and ascorbic acid supplementation

Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates—A Scoping Review of The Literature

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