RBC Storage Lesion Studies in Humans and Experimental Models of Shock

Abstract

The finding of toxicity in a meta-analysis of observational clinical studies of transfused longer stored red blood cells (RBC) and ethical issues surrounding aging blood for human studies prompted us to develop an experimental model of RBC transfusion. Transfusing older RBCs during canine pneumonia increased mortality rates. Toxicity was associated with in vivo hemolysis with release of cell-free hemoglobin (CFH) and iron. CFH can scavenge nitric oxide, causing vasoconstriction and endothelial injury. Iron, an essential bacterial nutrient, can worsen infections. This toxicity was seen at commonly transfused blood volumes (2 units) and was altered by the severity of pneumonia. Washing longer-stored RBCs mitigated these detrimental effects, but washing fresh RBCs actually increased them. In contrast to septic shock, transfused longer stored RBCs proved beneficial in hemorrhagic shock by decreasing reperfusion injury. Intravenous iron was equivalent in toxicity to transfusion of longer stored RBCs and both should be avoided during infection. Storage of longer-stored RBCs at 2 °C instead of higher standard temperatures (4–6 °C) minimized the release of CFH and iron. Haptoglobin, a plasma protein that binds CFH and increases its clearance, minimizes the toxic effects of longer-stored RBCs during infection and is a biologically plausible novel approach to treat septic shock.

Biopreservation and Reversal of Oxidative Injury During Blood Storage by a Novel Curcumin-based Gel Formulation

“…Preclinical models offer a unique opportunity to examine possible harmful effects of using RBC units nearing their storage expiry for transfusion that may not be readily available from human trials. Although preclinical studies do not provide predictions of the risk in actual clinical transfusions, they provide an understanding of the causes behind transfusion-related problems, and how RBC storage time, the number of RBC units used, and the patient's overall clinical condition, might be interconnected 1,44 .…”

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates—A Scoping Review of The Literature

“…The n = 138 excluded "reviews and meta-analyses" incorporated only n = 5 meta-analyses. Of those, three meta-analyses are based on clinical trials only, and one publication describes an animal model and includes a meta-analysis of clinical data in humans [69].…”