Improving red blood cell storage for trauma resusciation - Project Summary The long-term goal of our research is to increase our understanding of the mechanisms by which transfusion of stored pRBC units harms trauma patients and to mitigate these effects through improved pRBC storage. Trauma is the leading cause of death worldwide for those under 44 years of age. Hemorrhage accounts for 30-40% of these fatalities and is the most common potentially preventable cause of death from trauma. Survival after hemorrhage is dependent on surgical control of bleeding followed by resuscitation with red blood cells to replace intravascular volume and correct anemia. Packed red blood cells develop a series of biochemical and physical changes during storage that is collectively termed the red blood cell storage lesion. While there is no substitute for blood, rapid use of multiple units of aged red blood cells for resuscitation is harmful in severely injured patients, including increased multisystem organ failure, pneumonia, renal failure, sepsis, and death. Our previous work demonstrates that red blood cell units contain microparticles that mediate inflammatory events after hemorrhage and resuscitation and that decreasing their effect leads to a blunted inflammatory response and lung injury. Our data has also demonstrated that components of stored packed red blood cells lead to endothelial cell and leukocyte activation with resultant lung injury and microvascular thrombosis. We have confirmed that intervention to correct aspects of the red blood cell storage lesion and its effects leads to decreased harm after hemorrhage and resuscitation. We have also developed data that indicate that advanced glycation end products form during red blood cell storage and that a significant portion of the inflammatory response to resuscitation with older packed red blood cell units is mediated by the receptor for advanced glycation end products. We have also demonstrated that improvements in the storage environment and storage solutions will mitigate aspects of the red blood cell storage lesion. These findings, as well as the clinical need for improved packed red blood cells for resuscitation, have led us to propose two projects. Project 1 will seek to attenuate advanced glycation end product formation during packed red blood cell storage and the resulting effects during resuscitation after hemorrhage. Project 2 seeks to develop novel storage solutions to improve the quality of stored red blood cell units. With increased recent emphasis on the use of blood products for resuscitation from hemorrhagic shock, there is a crucial need to improve our understanding of the red blood cell storage lesion as well as potential strategies to mitigate harm from massive transfusion of older red blood cell units. If successful, the proposed work will address key gaps in our knowledge and clinical practice regarding a mechanistic understanding of the development and impact of the red blood cell storage lesion on the recipient during resuscitation as well as the need for novel storage solutions to attenuate the storage lesion and mitigate harm from massive transfusion of older pRBC units.
