Glucose‐6‐phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks

Francis, Richard O.; Jhang, Jeffrey S.; Pham, Huy P.; Hod, Eldad A.; Zimring, James C.; Spitalnik, Steven L.

doi:10.1111/vox.12068

Cited by 71 publications

(60 citation statements)

References 101 publications

(113 reference statements)

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“…Under normal circumstances, up to 92% of glucose is utilized in glycolysis to produce ATP, while under oxidative conditions 90% of glucose can be shunted through PPP to produce NADPH in order to maintain levels of reduced glutathione (GSH) [21–24]. PPP is responsible for the majority of NADPH produced in the cell, yielding 2 molecules of NADPH for each G6P molecule that enters the pathway.…”

Section: Resultsmentioning

confidence: 99%

Metabolomics of ADSOL (AS-1) Red Blood Cell Storage

Roback

Josephson

Waller

et al. 2014

Transfusion Medicine Reviews

109

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Background Population based investigations suggest that red blood cells (RBCs) are therapeutically effective when collected, processed and stored for up to 42 days under validated conditions prior to transfusion. However, some retrospective clinical studies have shown worse patient outcomes when transfused RBCs have been stored for the longest times. Furthermore, studies of RBC persistence in the circulation after transfusion have suggested that considerable donor-to-donor variability exists, and may affect transfusion efficacy. To understand the limitations of current blood storage technologies and to develop approaches to improve RBC storage and transfusion efficacy, we investigated the global metabolic alterations that occur when RBCs are stored in AS-1 (AS1-RBC). Methods Leukoreduced AS1-RBC units prepared from 9 volunteer research donors (12 total donated units) were serially sampled for metabolomics analysis over 42 days of refrigerated storage. Samples were tested by GC/MS and LC/MS/MS, and specific biochemical compounds were identified by comparison to a library of purified standards. Results Over three experiments, 185–264 defined metabolites were quantified in stored RBC samples. Kinetic changes in these biochemicals confirmed known alterations in glycolysis and other pathways previously identified in RBCs stored in SAGM (SAGM-RBC). Furthermore, we identified additional alterations not previously seen in SAGM-RBCs (e.g., stable pentose phosphate pathway flux, progressive decreases in oxidized glutathione), and we delineated changes occurring in other metabolic pathways not previously studied (e.g., S-adenosyl methionine cycle). These data are presented in the context of a detailed comparison with previous studies of SAGM-RBCs from human donors and murine AS1-RBCs. Conclusion Global metabolic profiling of AS1-RBCs revealed a number of biochemical alterations in stored blood that may affect RBC viability during storage as well as therapeutic effectiveness of stored RBCs in transfusion recipients. Significance These results provide future opportunities to more clearly pinpoint the metabolic defects during RBC storage, to identify biomarkers for donor screening and prerelease RBC testing, and to develop improved RBC storage solutions and methodologies.

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Section: Resultsmentioning

confidence: 99%

Metabolomics of ADSOL (AS-1) Red Blood Cell Storage

Roback

Josephson

Waller

et al. 2014

Transfusion Medicine Reviews

109

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“…Despite intrinsic differences in comparison to aging in vivo, biochemical analysis of RBC aging in vitro provides relevant clues about this process in the bloodstream. Likewise, metabolomics profiles of freshly withdrawn blood from healthy controls might serve as a baseline for future translational studies on hematologic infections (e.g., malaria) or diseases (e.g., sickle cell anemia or glucose‐6‐phosphate dehydrogenase deficiency). On the other hand, changes unique to RBC storage in vitro might inform biopreservation experts as to alternative strategies for extending the shelf life and improving the quality of RBCs or blood components, such as in the case of pathogen reduction technologies …”

Section: Discussionmentioning

confidence: 99%

Routine storage of red blood cell (RBC) units in additive solution‐3: a comprehensive investigation of the RBC metabolome

D’Alessandro

Nemkov

Kelher³

et al. 2014

Transfusion

130

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Background In most countries, packed 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 underway, impaired metabolism has been documented in RBCs stored in several additive solutions. Here we hypothesize that, despite reported beneficial effects, storage in additive solution-3 (AS-3) results in metabolic impairment weeks before the end of the unit shelf-life. Study design and Methods Five leukocyte-filtered AS-3 RBC units were sampled before, during and after leukoreduction at day0, and then assayed on a weekly basis from storage day1 through day42. RBC extracts and supernatants were assayed using a UHPLC-MS metabolomics workflow. Results Blood bank storage significantly affects metabolic profiles of RBC extracts and supernatants by day14. 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 additive solutions 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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“…Moreover, the importance of G6PD deficiency screening in blood donors prior to blood transfusion into a recipient during infection or treatment with an oxidative drug cannot be ignored, since blood transfusion from G6PD deficient donor may lead to adverse consequences in susceptible recipients [44]. …”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

et al. 2016

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Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear normal until exposed to oxidative stress which induces hemolysis. Consumption of certain foods such as fava beans, legumes; infection with bacteria or virus; and use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of RBCs in G6PD deficient individuals. The genetic defect that causes G6PD deficiency has been identified mostly as single base missense mutations. One hundred and sixty G6PD gene mutations, which lead to amino acid substitutions, have been described worldwide. The purpose of this study was to detect G6PD gene mutations in hospital-based settings in the local population of Dhaka city, Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity measurement using RANDOX G6PDH kit were performed for analysis of blood specimens and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was done with six sets of primers specific for G6PD gene. Automated Sanger sequencing of the PCR products was performed to identify the mutations in the gene. Based on fluorescence spot test and quantitative enzyme assay followed by G6PD gene sequencing, 12 specimens (11 males and one female) among 121 clinically suspected patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon-6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of coding sequence in one sample. These mutations either affect NADP binding or disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study of G6PD mutations in Bangladesh.

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Glucose‐6‐phosphate dehydrogenase deficiency in transfusion medicine: the unknown risks

Cited by 71 publications

References 101 publications

Metabolomics of ADSOL (AS-1) Red Blood Cell Storage

Metabolomics of ADSOL (AS-1) Red Blood Cell Storage

Routine storage of red blood cell (RBC) units in additive solution‐3: a comprehensive investigation of the RBC metabolome

Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in Bangladeshi Individuals

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