Another recent article that I finally had a chance to read and ruminate on: Danielle Qing and colleagues from have published an intriguing article in the December 1, 2014 issue of the American Journal of Critical Care and Respiratory Medicine, "Red Blood Cells Induce Necroptosis of Lung Endothelial Cells and Increase Susceptibility to Lung Inflammation." The article merits a read if you're interested in either transfusion medicine or lung pathology.
In both in vitro and murine models, RBC transfusion seems to prime lung inflammation through necroptosis (link to recent review article) of lung endothelial cells, followed by danger signal release of disease-associated molecular patterns, or DAMPs. A novel finding in this study is that necroptosis may be an important mechanism that for cellular damage and organ dysfunction that is clinically observed associated with RBC transfusion. The methodology of using human lung microvascular endothelial cells and human RBCs stored under clinical conditions makes this model of injury more potentially relevant at the clinical level since it likely is a better approximation of what is occurring in vivo.
However, these findings quite jibe with the results of the TRISS trial published in NEJM last October. One might expect that patients with sepsis who receive more RBC transfusions would have worse clinical outcomes than those who receive none or fewer transfusions. But in this study similar clinical outcomes (mortality at 90 days and rates of ischemic events and use of life support) were observed in ICU patients with severe sepsis between those who received RBC transfusion at liberal transfusion threshold versus a restrictive threshold, even though the latter group received more transfusions. It would be great to have a RCT that compared no to any RBC transfusions in this study population, measure necroptosis and DAMPs, and observe clinical outcomes.