Rejuvenation of allogenic red cells: benefits and risks

Aujla, Hardeep; Wozniak, Matthew A.; Kumar, Tracy; Murphy, Gavin J.; Investigators, Redjuvenate Trial

doi:10.1111/vox.12666

Cited by 7 publications

(6 citation statements)

References 58 publications

(64 reference statements)

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“…Rejuvenation did not alter antigenicity, and no bacterial contamination was detected in units rejuvenated during laboratory or operational phases. These changes were qualitatively and quantitatively similar to the results of RBC rejuvenation reported previously . Using the laboratory and early operational findings to set a trial component specification of key quality assurance metrics, RBCs then rejuvenated during an operational validation in a UK blood processing center were found to be compliant.…”

Section: Discussionsupporting

confidence: 77%

“…The manufacturing process for RBC rejuvenation described here results in units that reproducibly meet a specification comparable to that in previous clinical and experimental studies where rejuvenated RBCs have been shown to be safe and effective. RBCs with these properties following rejuvenation have been shown to have superior oxygen delivery and homeostatic and anti‐inflammatory effects relative to standard stored RBCs in experimental studies, as well as in limited clinical evaluations . In addition, key quality parameters for rejuvenation including ATP and 2,3 DPG were maintained to levels equivalent or superior to standard care units for at least 24 hours regardless of the age of units before rejuvenation.…”

Section: Discussionmentioning

confidence: 99%

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Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use

et al. 2019

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BACKGROUND: Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5 0 -triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery.STUDY DESIGN AND METHODS: Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37 C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution. A laboratory study was conducted on six pools of ABO/D-matched units made the day after donation. On Days 7, 21, and 28 of 4 AE 2 C storage, one unit per pool was rejuvenated and measured over 96 hours for volume, hematocrit, hemolysis, ATP, 2,3-DPG, supernatant potassium, lactate, and purines added (inosine) or produced (hypoxanthine) by rejuvenation. Subsequently, an operational validation (two phases of 32 units each) was undertaken, with results from the first informing a trial component specification applied to the second. Rejuvenation effects were also tested on crossmatch reactivity and RBC antigen profiles. RESULTS:Rejuvenation raised 2,3-DPG to, and ATP above, levels of fresh cells. The final component had potassium and hemolysis values below those of standard storage Days 7 and 21, respectively, containing 1.2% exogenous inosine and 500 to 1900 μmoles/unit of hypoxanthine. The second operational validation met compliance to the trial component specification. Rejuvenation did not adversely affect crossmatch reactivity or RBC antigen profiles. CONCLUSION:The validated rejuvenation process operates within defined quality limits, preserving RBC immunophenotypes, enabling manufacture for clinical trials. Abbreviations: AHG = anti-human globulin; 2,3-DPG = 2,3-diphosphoglycerate; ATP = adenosine 5 0 -triphosphate; Hb = hemoglobin; HCT = hematocrit; NHSBT = National Health Service Blood and Transplant; RCMV = RBC microvesicle; SAGM = saline adenine glucose mannitol solution; XM = serologic tube technique without anti-human globulin.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use

et al. 2019

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“…This causes the activation of the phosphatase three enzyme, which degrades 2,3-DPG, due to which the oxygen affinity of hemoglobin is increased, and less oxygen is transferred to tissue from the lungs by RBC (Bellelli and Brunori, 2020). Study shows that essentially no 2,3-DPG will remain after 21 days of storage in CPD and CPDA-1 (Aujla et al, 2018).…”

Section: Fig02mentioning

confidence: 99%

Effects of Anticoagulants on Blood Cells Morphology and Biochemistry

ARSHAD,

SAFDAR,

ATIF

et al. 2024

Biol Clin Sci Res J

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Blood is a particular type of connective tissue that majorly contains red blood cells (RBCs), white blood cells (WBCs), and platelets (Plts). Anticoagulants are used to preserve the fluidity of blood and retard morphological changes in blood cells. Anticoagulants like EDTA, heparin, sodium citrate, and CPDA-1 are used. However, these anticoagulants also have some disadvantages, summarized in this review. This chemical causes the lysis of many cells, including RBCs, and some of them, like EDTA, cause agglutination of platelets, which not only causes a decrease in platelet count but also causes a spurious increase in WBC count. These substances also alter the shapes of various cells present in blood. RBCs and platelets may become spherical from the normal biconcave disc and plate-like structures. Commonly used anticoagulants contribute to alterations of many hematological parameters, including hematocrit, hemoglobin concentration, and packed cell volume of RBCs. Certain chemicals used in anticoagulant solutions, such as potassium and sodium in EDTA solution, make the blood unsuitable for determining these electrolytes in the sample. They also induce many changes in the biochemical composition of the sample. The most affected biochemical changes are observed in 2,3-DPG, D-dimer concentration, blood gas estimation, and cytokine levels. As they contain different chemicals, they have varying pH, so they alter blood pH.

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“…Some of the most studied new strategies include the use of different additive solutions other than the commonly used [19] . For example, stored units can be added, with rejuvenating solutions containing pyruvate, inosine, phosphate, and adenine [51] or alkaline additives [41] , which, in metabolomics studies conducted by Gehrke et al [52] and D’Alessandro et al [53] , respectively, were found to be effective in restoring the energy and redox metabolism of RBCs. Another possible strategy is to supplement blood units with solutions containing antioxidant molecules such as vitamin E, which has been shown to reduce ROS formation [54] , or vitamin C and N-acetylcysteine, which support antioxidant mechanisms through the ascorbate oxidation and the synthesis of new glutathione, thus preventing oxidative injury and reducing hemolysis levels during storage [55] .…”

Section: Integrative Multiomics Approaches In Human Transfusion Medicinementioning

confidence: 99%

Omics Technologies in Veterinary Medicine: Literature Review and Perspectives in Transfusion Medicine

Miglio,

Cremonini,

Leonardi

et al. 2023

Transfus Med Hemother

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Background: Omics technologies represent a new analytical approach that allows a full cellular readout through the simultaneous analysis of thousands of molecules. The application of such technologies represents a flourishing field of research in human medicine, especially in transfusion medicine, while their application in veterinary medicine still needs to be developed. Summary: Omics technologies, especially proteomics, metabolomics, and lipidomics, are currently applied in several fields of human medicine. In transfusion medicine, the creation and integration of multiomics datasets have uncovered intricate molecular pathways occurring within blood bags during storage. In particular, the research has been directed toward the study of storage lesions (SLs), i.e., those biochemical and structural changes that red blood cells (RBCs) undergo during hypothermic storage, their causes, and the development of new strategies to prevent them. However, due to their challenges to perform and high costs, these technologies are hardly accessible to veterinary research, where their application dates back only to the last few years and thus a great deal of progress still needs to be made. As regards veterinary medicine, there are only a few studies that have focused mainly on fields such as oncology, nutrition, cardiology, and nephrology. Other studies have suggested omics datasets that provide important insights for future comparative investigations between human and nonhuman species. Regarding the study of storage lesions and, more generally, the veterinary transfusion field, there is a marked lack of available omics data and results with relevance for clinical practice. Key Messages: The use of omics technologies in human medicine is well established and has led to promising results in blood transfusion and related practices knowledge. Transfusion practice is a burgeoning field in veterinary medicine, but, to date, there are no species-specific procedures and techniques for the collection and storage of blood units and those validated in the human species are univocally pursued. Multiomics analysis of the species-specific RBCs’ biological characteristics could provide promising results both from a comparative perspective, by increasing our understanding of species suitable to be used as animal models, and in a strictly veterinary view, by contributing to the development of animal-targeted procedures.

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Rejuvenation of allogenic red cells: benefits and risks

Abstract: Transfusion of rejuvenated red cells reduces organ injury attributable to the red cell storage lesion without adverse effects in experimental studies in vivo. The clinical benefits of this intervention remain uncertain.

Cited by 7 publications

References 58 publications

Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use

Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use

Effects of Anticoagulants on Blood Cells Morphology and Biochemistry

Omics Technologies in Veterinary Medicine: Literature Review and Perspectives in Transfusion Medicine

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