Objective

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 haemoglobin and energy depletion. 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 patients participating in a randomised ctrl 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 hgb and iron were measured in blood. Leuk. invasion was determined by immunohistochemistry. The results were verified in vitro.

Results

Transfusion of stored RBC (~22d) into humans/pigs was associated with leuk. activation, and attenuated by washing. Unexpectedly, transfusion of washed RBC increased kidney injury, which correlated with high free hgb levels, oxidative stress (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. That was reduced by RBC rejuvenation.

Conclusion

Monocytes/platelets and endothelium are activated by oxidized lipids/MV and reactive free haem, respectively, and can be alleviated by RBC rejuvenation.