The potential adverse effects of transfusion of red blood cells after prolonged storage have been hotly debated. During refrigerated storage, red blood cells are damaged, a process known as the red blood cell "storage lesion." We hypothesized that the delivery of a bolus of iron derived from these rapidly cleared, damaged, red blood cells is responsible for some of the adverse effects of transfusion. Iron may play a role in producing a pro-inflammatory response to transfused red blood cells, potentially through the effects of reactive oxygen species on stress pathways and inflammasome activation. Furthermore, the excess iron may impair the host's ability to combat infection by its innate iron-withholding pathways. This symposium paper summarizes the background for the "iron hypothesis" as it relates to transfusion of red blood cells after prolonged refrigerated storage. It also includes a summary of the data from recent murine and human studies, and concludes with a discussion of several unresolved questions arising from these published studies.
[Show abstract][Hide abstract] ABSTRACT: Objective There is increasing awareness that allogeneic transfusion is potentially harmful in preterm neonates secondary to transfusion related immunomodulation (TRIM). Non-transferrin bound iron (NTBI) may contribute to TRIM by promoting oxidative damage and pro-inflammatory cytokine release. The current study aimed to determine if transfusion early in the neonatal period resulted in an increase in circulating NTBI, oxidative stress and immune activation.
Design Prospective observational study.
Setting One transfusion event was studied in infants ≤28 weeks gestation between 2 and 6 weeks postnatal age (n=33) admitted to a tertiary neonatal intensive care unit.
Methods Serum NTBI, inflammatory cytokines and malondialdehyde (MDA) were measured from the donor pack, prior to and at 2–4 and 24 h post-transfusion.
Results Median (range) age at transfusion was 17 (14–39) days with the pretransfusion haemoglobin level 9.6 (7.4–10.4) g/dl. NTBI was detectable in 18 (51%) of the transfusion packs. NTBI levels were higher after transfusion (p<0.01) returning to pretransfusion levels by 24 h. Post-transfusion NTBI level correlated with the age of transfused blood (p<0.001) and was positively correlated with plasma MDA (p=0.01) but not IL-1β, IL-6, IL8 or TNFα.
Conclusions Circulating NTBI is transiently elevated following blood transfusion in preterm newborns. This increase was related to the age of blood transfused and correlated with increases in oxidative stress but not pro-inflammatory cytokines. While further studies are necessary to determine whether these transient effects influence clinical outcome, the current data do not support a significant role in the very preterm neonate for NTBI in TRIM.
Archives of Disease in Childhood - Fetal and Neonatal Edition 03/2013; 98(5). DOI:10.1136/archdischild-2012-303353 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Red blood cell (RBC) transfusion is a lifesaving therapy, the logistic implementation of which requires RBC storage. However, stored RBCs exhibit substantial donor variability in multiple characteristics, including hemolysis in vitro and RBC recovery in vivo. The basis of donor variability is poorly understood. Study Design and Methods
We applied a murine model of RBC storage and transfusion to test the hypothesis that genetically distinct inbred strains of mice would demonstrate strain-specific differences in RBC storage. In vivo recoveries were determined by monitoring transfused RBCs over 24 hours. Timed aliquots of stored RBCs were subjected to tandem chromatography/mass spectrometry analysis to elucidate metabolic changes in the RBCs during storage. ResultsUsing independent inbred mouse strains as donors, we found substantial strain-specific differences in posttransfusion RBC recovery in vivo after standardized refrigerated storage in vitro. Poor posttransfusion RBC recovery correlated with reproducible metabolic variations in the stored RBC units, including increased lipid peroxidation, decreased levels of multiple natural antioxidants, and accumulation of cytidine. Strain-dependent differences were also observed in eicosanoid generation (i.e., prostaglandins and leukotrienes). Conclusion
These findings provide the first evidence of strain-specific metabolomic differences after refrigerated storage of murine RBCs. They also provide the first definitive biochemical evidence for strain-specific variation of eicosanoid generation during RBC storage. The molecules described that correlate with RBC storage quality, and their associated biochemical pathways, suggest multiple causal hypotheses that can be tested regarding predicting the quality of RBC units before transfusion and developing methods of improved RBC storage.
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