Both “stored PRBC” and “stored molarity calculator PLT” display increased ability to prime fMLP-induced neutrophil …DiscussionThe development of respiratory dysfunction compromises the recovery of severely ill patients and may contribute to their morbidity and death. While some patients may progress to either ALI or ARDS, the association with recent blood transfusion may be overlooked [20-22]. Thus, many cases of ALI/ARDS may in fact represent TRALI, and the true scale of the risks posed by TRALI in the critical care setting are likely to be under-appreciated. Prospective studies have revealed an incidence of TRALI ranging from 5 to 8% in general critical care patients [23,24] and up to 29% in ELSD critical care patients admitted with GI bleeding [25].

This study provides additional evidence that both patient and blood product factors contribute to the development of TRALI, and that the type of blood product influences the severity of injury.Patients with severe illness are hypothesised to be more likely to develop TRALI, thus critically ill patients may be particularly susceptible to the development of TRALI [14,22]. In this study, TRALI only developed in “ill” sheep and did not develop in any of the “healthy” sheep, even following transfusion of “stored PRBC.” This is consistent with previous TRALI models, in which both a clinical first event, either LPS-infusion or, in the case of mice, their exposure to a germ environment, and an appropriate second event (that is, stored blood or leucocyte antibody) were required for TRALI to develop [9,10,12,38,39].

Thus, this study reaffirms the importance of patient factors in the development of TRALI.The age of the transfused blood product was also found to be crucial to the development of TRALI, as it predominantly developed in LPS-primed sheep transfused with “stored PRBC” and not “fresh PRBC.” This adds to findings from previous in vivo models in which TRALI has been described subsequent to transfusion with supernatant from stored human PRBC in rats [12] or stored human PLT in both rats [40] and in sheep [10]. During routine storage of PRBC and PLT, proteins and lipids (or their metabolites) are released by cells into the storage medium [28-31,41,42]. These soluble factors are retained in the supernatant and are thought to contribute to the development of TRALI [1-3,5,6,11,12,28-31,43-45], although some studies have also implicated the transfused cells [44,46].

In this study, cytokine array and ELISA analyses were used to identify the soluble factors that GSK-3 may have contributed to the development of TRALI in the sheep. It was demonstrated that “stored PRBC” contained higher levels of EGF, ENA-78, GRO-��, IL-8, IL-16 and MCP-1 relative to “fresh PRBC”, while levels of lactate and potassium increased and levels of sodium decreased.