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      Effect of red blood cell storage time on markers of hemolysis and inflammation in transfused very low birth weight infants

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          Abstract

          Background

          Prolonged storage of transfused red blood cells (RBCs) is associated with hemolysis in healthy adults and inflammation in animal models. We aimed to determine whether storage duration affects markers of hemolysis (e.g., serum bilirubin, iron, and non-transferrin-bound iron (NTBI)) and inflammation (e.g., interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1) in transfused very low birth weight (VLBW) infants.

          Methods

          Blood samples from 23 independent transfusion events were collected by heel stick before and 2–6h after transfusion.

          Results

          Serum iron, total bilirubin, NTBI, and MCP-1 levels were significantly increased after transfusion of RBCs (P<0.05 for each comparison). The storage age of transfused RBCs positively correlated with increases in NTBI following transfusion (P<0.001; R 2 = 0.44). No associations between storage duration and changes in the other analytes were observed.

          Conclusions

          Transfusion of RBCs into VLBW infants is associated with increased markers of hemolysis and the inflammatory chemokine MCP-1. RBC storage duration only correlated with increases in NTBI levels following transfusion. NTBI was only observed in healthy adults following 35 days of storage; however, this study suggests that VLBW infants are potentially more susceptible to producing this pathological form of iron, with increased levels observed after transfusion of only 20-day old RBCs.

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          Most cited references37

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          Non-transferrin bound iron: a key role in iron overload and iron toxicity.

          Besides transferrin iron, which represents the normal form of circulating iron, non-transferrin bound iron (NTBI) has been identified in the plasma of patients with various pathological conditions in which transferrin saturation is significantly elevated. To show that: i) NTBI is present not only during chronic iron overload disorders (hemochromatosis, transfusional iron overload) but also in miscellaneous diseases which are not primarily iron overloaded conditions; ii) this iron species represents a potentially toxic iron form due to its high propensity to induce reactive oxygen species and is responsible for cellular damage not only at the plasma membrane level but also towards different intracellular organelles; iii) the NTBI concept may be expanded to include intracytosolic iron forms which are not linked to ferritin, the major storage protein which exerts, at the cellular level, the same type of protective effect towards the intracellular environment as transferrin in the plasma. Plasma NTBI and especially labile plasma iron determinations represent a new important biological tool since elimination of this toxic iron species is a major therapeutic goal. The NTBI approach represents an important mechanistic concept for explaining cellular iron excess and toxicity and provides new important biochemical diagnostic tools. This article is part of a Special Issue entitled Transferrins: Molecular mechanisms of iron transport and disorders. Copyright © 2011 Elsevier B.V. All rights reserved.
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            Is Open Access

            Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants

            SUMMARY Necrotizing enterocolitis (NEC) afflicts approximately 10% of extremely preterm infants with high fatality. Inappropriate bacterial colonization with Enterobacteriaceae is implicated, but no specific pathogen has been identified. We identify uropathogenic E. coli (UPEC) colonization as a significant risk factor for the development of NEC and subsequent mortality. We describe a large-scale deep shotgun metagenomic sequence analysis of the early intestinal microbiome of 144 preterm and 22 term infants. Using a pan-genomic approach to functionally subtype the E. coli, we identify genes associated with NEC and mortality that indicate colonization by UPEC. Metagenomic multilocus sequence typing analysis further defined NEC-associated strains as sequence types often associated with urinary tract infections, including ST69, ST73, ST95, ST127, ST131, and ST144. Although other factors associated with prematurity may also contribute, this report suggests a link between UPEC and NEC and indicates that further attention to these sequence types as potential causal agents is needed.
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              Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron.

              Transfusions of RBCs stored for longer durations are associated with adverse effects in hospitalized patients. We prospectively studied 14 healthy human volunteers who donated standard leuko-reduced, double RBC units. One unit was autologously transfused "fresh" (3-7 days of storage), and the other "older" unit was transfused after 40 to 42 days of storage. Of the routine laboratory parameters measured at defined times surrounding transfusion, significant differences between fresh and older transfusions were only observed in iron parameters and markers of extravascular hemolysis. Compared with fresh RBCs, mean serum total bilirubin increased by 0.55 mg/dL at 4 hours after transfusion of older RBCs (P = .0003), without significant changes in haptoglobin or lactate dehydrogenase. In addition, only after the older transfusion, transferrin saturation increased progressively over 4 hours to a mean of 64%, and non-transferrin-bound iron appeared, reaching a mean of 3.2μM. The increased concentrations of non-transferrin-bound iron correlated with enhanced proliferation in vitro of a pathogenic strain of Escherichia coli (r = 0.94, P = .002). Therefore, circulating non-transferrin-bound iron derived from rapid clearance of transfused, older stored RBCs may enhance transfusion-related complications, such as infection.
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                Author and article information

                Journal
                0100714
                6400
                Pediatr Res
                Pediatr. Res.
                Pediatric research
                0031-3998
                1530-0447
                23 July 2017
                16 August 2017
                December 2017
                16 February 2018
                : 82
                : 6
                : 964-969
                Affiliations
                [1 ]Division of Neonatology, Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461
                [2 ]Division of Neonatology, Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York 10032
                [3 ]Division of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, IL
                [4 ]Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032
                Author notes
                Correspondence: Eldad A. Hod, M.D., Department of Pathology and Cell Biology, 630 West 168th St, Room P&S 14-434, Laboratory of Transfusion Biology, College of Physicians & Surgeons of Columbia University, New York, NY 10032; Phone: 212-342-5648; eh2217@ 123456cumc.columbia.edu
                Article
                NIHMS893658
                10.1038/pr.2017.177
                5685900
                28738026
                b919f1d4-aeb7-4318-a206-6b01c2101d35

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                Pediatrics
                Pediatrics

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