Abstract 19379: Red Blood Cell Washing Increases Kidney Injury in Cardiac Surgery Patients - The Role of Oxidised Lipids and Oxidative Stress
Introduction: Allogeneic red blood cell (RBC) transfusion in cardiac surgery patients increases the risk of pulmonary and renal morbidity. These associations are attributable to the ‘storage lesion’ - accumulation of metabolites in the RBC supernatant that includes pro-inflammatory lipids, cell-free hemoglobin and energy depletion. Hypothesis: Storage lesion components trigger different events that lead to organ injury. Reducing storage lesion by RBC washing or rejuvenation will reduce organ injury. Methods: Samples from 60 cardiac patients participating in a randomized controlled trial of RBC washing prior to transfusion versus standard care were analysed for inflammatory markers. In a complementary experiment, 4 groups of pigs received crystalloid infusion or 14-day old RBC that were left untreated, washed or rejuvenated (Rejuvesol, Citra Labs, IN). Inflammatory markers, free hemoglobin and iron were measured in blood. Leukocyte invasion was determined by immunohistochemistry. The results were verified and further analysed in an in vitro inflammatory model. Results: Transfusion of stored RBC (~22 days) into humans or pigs was associated with leukocyte activation, and attenuated by washing. That was attributed to oxidised lipids on transfused RBC derived microvesicles that activated monocytes and platelets, as revealed in depletion experiments. Unexpectedly, transfusion of washed RBC increased kidney injury, which correlated with higher free haemoglobin levels, oxidative stress (confirmed by HMOX-1 levels and protein carbonylation), and endothelial injury in washed RBC recipients. Oxidative stress triggered non-standard endothelial activation defined by expression of VLA5 and fibronectin retention. Either pathway was reduced when rejuvenated blood was transfused. Conclusion: Monocytes/platelets and endothelium are activated by oxidized lipids/MV and reactive free haem, respectively, and can be alleviated by RBC rejuvenation.