Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient

Kanias, Tamir; Gladwin, Mark T.

doi:10.1111/j.1537-2995.2012.03748.x

Cited by 51 publications

(58 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These changes include the depletion of adenosine triphosphate (ATP) and 2,3‐diphosphoglycerate (2,3‐DPG), reduced blood flow velocity and increased endothelial adhesion, progressive membrane dysfunction leading to hemolysis, elaboration of lipid mediators, microparticle formation, and disruptive effects on nitric oxide (NO)‐mediated vasodilation . In particular, we and others proposed saRBC‐mediated reductions in NO bioavailability and inhibition of NO‐mediated vasodilation as potentially important mechanisms underlying adverse transfusion effects . We demonstrated in rat aortic rings that compared to fresh RBCs, saRBCs that were stored for 28 to 42 days produced significant inhibition of methacholine‐stimulated and NO‐mediated vasodilation .…”

mentioning

confidence: 87%

Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients

et al. 2014

View full text Add to dashboard Cite

Background Clinical and animal studies indicate that transfusions of older stored RBCs impair clinical outcomes as compared to fresh RBC transfusions. It has been suggested that this effect is due to inhibition of NO-mediated vasodilation following transfusion of older RBC units. However, to date this effect has not been identified in human transfusion recipients. Study Design and Methods Forty-three hospitalized patients with transfusion orders were randomized to receive either fresh (< 14 days) or older stored (> 21 days) RBC units. Prior to transfusion, and at selected time points after the start of transfusion, endothelial function was assessed using non-invasive flow-mediated dilation assays. Results Following transfusion of older RBC units, there was a significant reduction in NO-mediated vasodilation at 24 hours after transfusion (p=0.045), while fresh RBC transfusions had no effect (p=0.231). Conclusions The present study suggests for the first time a significant inhibitory effect of transfused RBC units stored > 21 days on NO-mediated vasodilation in anemic hospitalized patients. This finding lends further support to the hypothesis that deranged NO signaling mediates adverse clinical effects of older RBC transfusions. Future investigations will be necessary to address possible confounding factors and confirm these results.

show abstract

mentioning

confidence: 87%

Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The use of inhaled nitric oxide or administration of haptoglobin to counteract cell-free hemoglobin is under investigation [86,108,109,[125][126][127]. Development of synthetic hemoglobin-based oxygen carriers continues to be an active area of research despite the many biochemical challenges to overcome the toxic characteristics of native hemoglobin .…”

Section: Future Directionsmentioning

confidence: 99%

“…Interest in the possible intersection of storage-related RBC changes and trauma has sparked new laboratory-based research to investigate the potential immune and vascular effects resulting from transfusion of longer stored RBCs in critically ill patients [83,84]. A "two-insult" model of posttransfusion injury has been suggested by several investigators as a working hypothesis [85][86][87][88]. This model proposes that the first insult is the patient's underlying immunomodulatory condition (eg, trauma injury) that primes the patient's immune-vascular system and a second inflammatory insult triggers full-scale activation that broadens the injurious state.…”

Section: Red Blood Cell Storage Lesion and Potential Consequences Formentioning

confidence: 99%

Red Blood Cell Storage Duration and Trauma

Sparrow

2015

Transfusion Medicine Reviews

View full text Add to dashboard Cite

“…1 A growing number of studies have discussed the potential impact of donor characteristics on RBC storage lesions 2 and posttransfusion outcomes, 3–7 which led to the scrutiny of genetic and biological factors in blood donors that may contribute to variations in the quality of RBC units. Although the clinical consequences of such differences have not been established in humans, studies in mice have demonstrated strain-specific susceptibility to RBC injury from cold storage that correlates with posttransfusion RBC recovery and function.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

Genetic polymorphisms in blood donors may contribute to donor-specific differences in the survival of red blood cells (RBCs) during cold storage and after transfusion. Genetic variability is anticipated to be high in donors with racial admixture from malaria endemic regions such as Africa and Asia. The purpose of this study was to test the hypothesis that donor genetic background, reflected by sex and self-reported ethnicity, significantly modulates RBC phenotypes in storage. High throughput hemolysis assays were developed and used to evaluate stored RBC samples from 11 115 African American, Asian, white, and Hispanic blood donors from 4 geographically diverse regions in the United States. Leukocyte-reduced RBC concentrate-derived samples were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Male sex was strongly associated with increased susceptibility to all 3 hemolysis measures (P < .0001). African American background was associated with resistance to osmotic hemolysis compared with other racial groups (adjusted P < .0001). Donor race/ethnicity was also associated with extreme (>1%) levels of storage hemolysis exceeding US Food and Drug Administration regulations for transfusion (hemolysis >1% was observed in 3.51% of Asian and 2.47% of African American donors vs 1.67% of white donors). These findings highlight the impact of donor genetic traits on measures of RBC hemolysis during routine cold storage, and they support current plans for genome-wide association studies, which may help identify hereditable variants with substantive effects on RBC storage stability and possibly posttransfusion outcomes.

show abstract

Nitric oxide, hemolysis, and the red blood cell storage lesion: interactions between transfusion, donor, and recipient

Cited by 51 publications

References 28 publications

Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients

Effects of storage‐aged red blood cell transfusions on endothelial function in hospitalized patients

Red Blood Cell Storage Duration and Trauma

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

Contact Info

Product

Resources

About