Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study

Kanias, Tamir; Lanteri, Marion C.; Page, Grier P.; Guo, Yuelong; Endres, Stacy; Stone, Mars; Keating, Sheila M.; Mast, Alan E.; Cable, Ritchard G.; Triulzi, Darrell J.; Kiss, Joseph E.; Murphy, Edward L.; Kleinman, Steve; Busch, Michael P.; Gladwin, Mark T.

doi:10.1182/bloodadvances.2017004820

Cited by 171 publications

(292 citation statements)

References 34 publications

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“…43,52 Future studies will address the correlations of the present findings with those variables, as well as the propensity to hemolyze in several in-vitro hemolytic assays and with donor genetics. Analyses are also planned to determine the in vivo consequences of these findings following transfusions of RBC components from RBC-Omics donors into recipients represented in the REDS-III linked donor-recipient database.…”

Section: Discussionmentioning

confidence: 87%

“…Donor selection criteria and recruitment procedures for RBC-Omics were previously described by Kanias et al 43 Donors were enrolled at the American Red Cross (ARC - Farmington, CT), the Institute for Transfusion Medicine (ITxM - Pittsburgh, PA), Blood Center of Wisconsin (BCW - Milwaukee, WI), and Blood Centers of the Pacific (BCP/BSRI - San Francisco, CA). Of 14,520 consenting donors, 13,770 (95%) were classified as fully enrolled after successfully donating a whole blood unit.…”

Section: Methodsmentioning

confidence: 99%

“…43 Donors whose RBCs were at the extreme end of storage hemolytic phenotypes were recalled for a second donation, from which RBCs were manufactured according to standard operational procedures at each blood center and then stored under routine blood bank conditions and sampled at storage days 10, 23 and 42 to test for spontaneous, oxidative, osmotic and mechanical hemolysis in vitro . Metabolomics analysis was performed on a total of 599 samples from 250 recalled donors.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

et al. 2018

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Background Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multi-center study. Study design and Methods Within the framework of the REDS-III RBC-Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23 and 42 days prior to sample acquisition for metabolomics analyses. Results Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (AS-1 vs AS-3) used in the different hubs. Samples stored in mannitol-free/citrate-loaded AS-3 were characterized by elevated levels of high-energy compounds, improved glycolysis and glutathione homeostasis. Increased methionine metabolism and activation of the trans-sulfuration pathway was noted in samples processed in the center using AS-1. Conclusion Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multi-center metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.

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Section: Discussionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

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“…One aliquot was used for the quantification of spontaneous storage hemolysis and the other for the stress-induced hemolysis assays as described before. 4 Percent end-of-storage hemolysis was determined according to the following equation:

Storage hemolysis (%) = \frac{(100 - H C T) \times H b_{s u p e r n a t a n t}}{H b_{t o t a l}}

Sample hematocrit (HCT) was determined by collecting blood samples into capillary tubes, which were centrifuged in a micro-HCT centrifuge (LW Scientific, Lawrenceville, GA). Hb supernatant refers to the levels of free hemoglobin obtained after centrifugation (1500x g, 10min, 18°C) measured in the supernatant.…”

Section: Methodsmentioning

confidence: 99%

Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis

et al. 2018

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Background Frequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racial-ethnically diverse population of blood donors. Study design Leukocyte-reduced RBC concentrate-derived samples from 13,403 donors were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self-reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject. Results Frequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1±5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p<0.0001) in multivariate analyses correcting for age, sex and race-ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p<0.0001 for all), whereas self-reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p<0.0001 for both). Conclusions Frequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron deficient donors. Further investigation is necessary to assess post-transfusion safety and efficacy in patients receiving these RBC products.

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“…Inherent biologic differences in RBCs affecting their survival have been reported with higher hemolysis after prolonged storage in leukocytereduced RBC concentrate derived from male donors (7). Furthermore, ethnic background was associated with resistance to osmotic hemolysis as well as extreme (>1%) levels of storage hemolysis, exceeding The US Food and Drug Administration regulations (15).…”

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confidence: 91%

Mortality after red blood cell transfusions from previously pregnant donors: complexities in the interpretation of large data

Kuldanek

Silliman

2018

J. Thorac. Dis.

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Red blood cell (RBC) transfusion is a common and potentially life-saving intervention. The requirement for RBC transfusions inherently reflects a degree of illness in the recipient, and healthy individuals do not generally require blood transfusions. In the recent past, restrictive blood transfusion policies have improved patient outcomes with the added benefit of driving down medical costs (1). Other policies and advances in cell preservation technology such as ABO and Rh matching, leukoreduction and limitations in the age of storage (to the age of RBC viability) of blood products have decreased recipient morbidity and mortality (1-3). However, the concept that RBC donor female gender and parity may influence recipient mortality has been a subject of much debate in the blood banking community and differing conclusions are reported in several large retrospective studies (4,5). Here we comment on the recent article by published inJAMA reporting increased mortality in male recipients of RBC units from female donors who had ever been pregnant compared with male recipients of RBC units from male donors.In this retrospective cohort study of first ever RBC transfusion recipients, the authors aimed to "quantify the association between RBC transfusion from female blood donors, with and without a history of pregnancy, and patient mortality in female and male transfusion recipients." They utilized three methodologies analyzing mortality results over a 10-year follow-up period in 42,132 recipients of RBC transfusions.The primary methodology, utilizing a "no-donor-mixture" cohort, was designed to prevent dilution effects by censoring or excluding recipient data when RBC products from more than one donor type were given. In these analyses, 31,118 recipients received 59,320 units from predominantly male (88%) donors. Never-pregnant female (NPF) and everpregnant female (EPF) RBC units comprised 6% each of the total donor pool. The second methodology utilized recipients who received only a single RBC unit (16,959 recipients). Finally, the third methodology utilized the full cohort, including recipients of multiple donor unit types. In the Netherlands, all transfusion information and mortality data are tracked within a national registry that includes age, gender, and dates of death but excludes information about ethnicity/race. All blood products were leukocyte-reduced by pre-storage filtration. Pregnancy status was obtained via self-reporting and due to an unknown pregnancy status, 44% of the donations from females were not used. All other transfused products were ignored in the primary analyses.There were 3,969 deaths over a 10-year follow-up period within the "no-mixture" cohort. Cox proportional hazards models were utilized and categorical variables were fit into the model to correct for potential confounding. These potential confounders included institution, ABORhD blood group, age of the donor, and cumulative number of transfusions. Resulting hazard ratios (HRs) were calculated for each of the two exposure groups (i.e., ...

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Ethnicity, sex, and age are determinants of red blood cell storage and stress hemolysis: results of the REDS-III RBC-Omics study

Cited by 171 publications

References 34 publications

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis

Mortality after red blood cell transfusions from previously pregnant donors: complexities in the interpretation of large data

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