Towards microfluidic-based depletion of stiff and fragile human red cells that accumulate during blood storage

In this study, the effects of prolonged storage on several biophysical properties of red blood cells (RBCs) were investigated. Single cell deformability was used as an important criterion in determining subgroups of RBCs evolved during storage lesion. A deformability-based microfluidic cell sorting technology was applied, which demonstrates the ability to enrich and separate the less deformable subpopulations of stored blood. These less deformable RBC subpopulations were then associated with other important markers such as osmotic fragility indicating cell integrity as well as microparticle content. This work demonstrates a systematic methodology to both monitor and improve banked blood quality, thereby reducing risks related to blood transfusion.United States. Defense Advanced Research Projects Agency (N66001-11-1-4182

Additive effects of blood donor smoking and gamma irradiation on outcome measures of red blood cell transfusion

BACKGROUND: Recent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin levels in patients following red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes. STUDY DESIGN AND METHODS: We linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined hemoglobin increments and subsequent transfusion requirements following single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors. RESULTS: We linked data on 4,038 transfusion recipients who received one or more single-unit RBC transfusions (n=5,086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n=326), hemoglobin increments were reduced following transfusion of gamma irradiated units (0.76 g/dL; p=0.033) but not unirradiated units (1.04 g/dL; p=0.54) compared to those from non-smokers (1.01 g/dL; n=4,760). In parallel with changes in hemoglobin levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (OR 2.49; p=0.01) but not unirradiated RBC units (OR 1.10; p=0.52). CONCLUSION: Donor smoking was associated with reduced hemoglobin increments and the need for additional transfusions in recipients of gamma irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion

Blood donor obesity is associated with changes in red blood cell metabolism and susceptibility to hemolysis in cold storage and in response to osmotic and oxidative stress

BackgroundObesity is a global pandemic characterized by multiple comorbidities, including cardiovascular and metabolic diseases. The aim of this study was to define the associations between blood donor body mass index (BMI) and RBC measurements of metabolic stress and hemolysis.Study design and methodsThe associations between donor BMI (<25 kg/m2 , normal weight; 25-29.9 kg/m2 , overweight; and ≥30 kg/m2 , obese) and hemolysis (storage, osmotic, and oxidative; n = 18 donors) or posttransfusion recovery (n = 14 donors) in immunodeficient mice were determined in stored leukocyte-reduced RBC units. Further evaluations were conducted using the National Heart, Lung, and Blood Institute RBC-Omics blood donor databases of hemolysis (n = 13 317) and metabolomics (n = 203).ResultsEvaluations in 18 donors revealed that BMI was significantly (P < 0.05) and positively associated with storage and osmotic hemolysis. A BMI of 30 kg/m2 or greater was also associated with lower posttransfusion recovery in mice 10 minutes after transfusion (P = 0.026). Multivariable linear regression analyses in RBC-Omics revealed that BMI was a significant modifier for all hemolysis measurements, explaining 4.5%, 4.2%, and 0.2% of the variance in osmotic, oxidative, and storage hemolysis, respectively. In this cohort, obesity was positively associated (P < 0.001) with plasma ferritin (inflammation marker). Metabolomic analyses on RBCs from obese donors (44.1 ± 5.1 kg/m2 ) had altered membrane lipid composition, dysregulation of antioxidant pathways (eg, increased oxidized lipids, methionine sulfoxide, and xanthine), and dysregulation of nitric oxide metabolism, as compared to RBCs from nonobese (20.5 ± 1.0 kg/m2 ) donors.ConclusionsObesity is associated with significant changes in RBC metabolism and increased susceptibility to hemolysis under routine storage of RBC units. The impact on transfusion efficacy warrants further evaluation

Nicotine exposure increases markers of oxidant stress in stored red blood cells from healthy donor volunteers

BACKGROUND: Cigarette smoking is a frequent habit across blood donors (approx. 13% of the donor population), that could compound biologic factors and exacerbate oxidant stress to stored red blood cells (RBCs). STUDY DESIGN AND METHODS: As part of the REDS-III RBC-Omics (Recipient Epidemiology Donor Evaluation Study III Red Blood Cell-Omics) study, a total of 599 samples were sterilely drawn from RBC units stored under blood bank conditions at Storage Days 10, 23, and 42 days, before testing for hemolysis parameters and metabolomics. Quantitative measurements of nicotine and its metabolites cotinine and cotinine oxide were performed against deuterium-labeled internal standards. RESULTS: Donors whose blood cotinine levels exceeded 10 ng/mL (14% of the tested donors) were characterized by higher levels of early glycolytic intermediates, pentose phosphate pathway metabolites, and pyruvate-to-lactate ratios, all markers of increased basal oxidant stress. Consistently, increased glutathionylation of oxidized triose sugars and lipid aldehydes was observed in RBCs donated by nicotine-exposed donors, which were also characterized by increased fatty acid desaturation, purine salvage, and methionine oxidation and consumption via pathways involved in oxidative stress-triggered protein damage-repair mechanisms. CONCLUSION: RBCs from donors with high levels of nicotine exposure are characterized by increases in basal oxidant stress and decreases in osmotic hemolysis. These findings indicate the need for future clinical studies aimed at addressing the impact of smoking and other sources of nicotine (e.g., nicotine patches, snuff, vaping, secondhand tobacco smoke) on RBC storage quality and transfusion efficacy