Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization

Stowell, Sean R.; Smith, Nicole H.; Zimring, James C.; Fu, Xiaoyun; Palmer, Andre F.; Fontes, Jorge; Banerjee, Uddyalok; Yazer, Mark H.

doi:10.1111/trf.12106

Cited by 50 publications

(54 citation statements)

References 40 publications

(87 reference statements)

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“…32 In vivo studies in mice have shown that vitamin C supplementation can improve storage as measured by 24-h recovery. 33 The generation of products of lipid oxidation not only gives insight into underlying RBC storage biology, but may in themselves represent a biologically significant component of transfused RBCs. Among the lipid oxidation products that were observed to both increase with…”

Section: Discussionmentioning

confidence: 99%

Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells

Wolski

Dumont³

et al. 2016

Haematologica

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T ransfusion of red blood cells is a very common inpatient procedure, with more than 1 in 70 people in the USA receiving a red blood cell transfusion annually. However, stored red blood cells are a non-uniform product, based upon donor-to-donor variation in red blood cell storage biology. While thousands of biological parameters change in red blood cells over storage, it has remained unclear which changes correlate with function of the red blood cells, as opposed to being co-incidental changes. In the current report, a murine model of red blood cell storage/transfusion is applied across 13 genetically distinct mouse strains and combined with high resolution metabolomics to identify metabolic changes that correlated with red blood cell circulation post storage. Oxidation in general, and peroxidation of lipids in particular, emerged as changes that correlated with extreme statistical significance, including generation of dicarboxylic acids and monohydroxy fatty acids. In addition, differences in anti-oxidant pathways known to regulate oxidative stress on lipid membranes were identified. Finally, metabolites were identified that differed at the time the blood was harvested, and predict how the red blood cells perform after storage, allowing the potential to screen donors at time of collection. Together, these findings map out a new landscape in understanding metabolic changes during red blood cell storage as they relate to red blood cell circulation. ABSTRACT

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Section: Discussionmentioning

confidence: 99%

Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells

Wolski

Dumont³

et al. 2016

Haematologica

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“…The samples were also stained with a primary Ab, MIMA29, an anti-Fy6 Ab, or an anti-GPA Ab at a concentration of 1 mg/100 ml in FACS buffer (2% BSA, 0.9% EDTA in PBS), then with a secondary Ab, goat anti-mouse Igs (BD Biosciences Pharmingen), diluted 1:100 in FACS buffer, as outlined previously (31). The samples were also stained with Rat anti-TER119 (BD Biosciences Pharmingen), also diluted to 1:100 with FACS buffer; Rat IgG2b k (BD Biosciences Pharmingen) Abs were used as an isotype-matched control.…”

Section: Rbc Characterizationmentioning

confidence: 99%

Antigen Modulation Confers Protection to Red Blood Cells from Antibody through Fcγ Receptor Ligation

Stowell

Liepkalns

Hendrickson

et al. 2013

The Journal of Immunology

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Autoantibodies and alloantibodies can damage self-tissue or transplanted tissues through either fixation of complement or ligation of FcγRs. Several pathways have been described that imbue self-tissues with resistance to damage from complement fixation, as a protective measure against damage from these Abs. However, it has been unclear whether parallel pathways exist to provide protection from FcγR ligation by bound Abs. In this article, we describe a novel pathway by which cell surface Ag is specifically decreased as a result of Ab binding (Ag modulation) to the extent of conferring protection to recognized cells from Fcγ-dependent clearance. Moreover, the Ag modulation in this system requires FcγR ligation. Together, these findings provide unique evidence of self-protective pathways for FcγR-mediated Ab damage.

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“…Unit age and storage solution were included as study variables because RBCs undergo a number of physical and biochemical changes during their storage that may be pro-inflammatory to a transfusion recipient, as observed in murine models (Hendrickson et al, 2010(Hendrickson et al, , 2011Stowell et al, 2013).…”

Section: Methodsmentioning

confidence: 99%

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

et al. 2014

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SummarySickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro-inflammatory SCD-related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro-inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion-associated pro-inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty-two patients received 3166 pre-storage leuco-reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso-occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate-phosphate-dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro-inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

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Addition of ascorbic acid solution to stored murine red blood cells increases posttransfusion recovery and decreases microparticles and alloimmunization

Abstract: These data indicate that the addition of ascorbic acid solution to RBCs during storage has a beneficial effect on recovery and immunogenicity of RBCs, but not cytokine induction. The addition of ascorbic acid (or other antioxidants) to human RBCs may have beneficial effects.

Cited by 50 publications

References 40 publications

Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells

Metabolic pathways that correlate with post-transfusion circulation of stored murine red blood cells

Antigen Modulation Confers Protection to Red Blood Cells from Antibody through Fcγ Receptor Ligation

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease

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