Metabolomic profiling highlights oxidative damages in platelet concentrates treated for pathogen inactivation and shows protective role of urate

Introduction Research in transfusion medicine is motivated by the desire to deliver the most-compatible and most-efficient blood product to the patient. It is now well accepted that ex vivo platelet concentrates (PCs) experience biochemical alterations and a functional decline known as storage lesions. Photochemical treatments have been introduced to secure PCs against pathogens but are reported to accelerate these lesions. Objectives The objective of this study was to investigate metabolic changes in stored PCs treated for pathogen inactivation with the INTERCEPT Blood system (Cerus, Concord, USA). Methods PCs either untreated (uPCs) or INTERCEPT-treated (iPCs) were sampled along the 7-day storage period. First, metabolites were extracted and analyzed using ultra-high pressure liquid chromatography-high resolution mass spectrometry followed by statistical analysis. Secondly, we investigated the role of urate, a major plasma antioxidant, in the platelet function using flow cytometry-based assays. Results We observed oxidative damages in stored iPCs compared to uPCs, in particular alteration of the purine and the glutathione metabolism. We showed diminution of antioxidant defenses following INTERCEPT treatment such as the conversion of urate to allantoin, only possible in humans under the action of reactive oxygen species (ROS). Functional assays on platelets in absence or in an excess of urate suggest a protective role of urate in PCs. Conclusion Our results indicate oxidative damages occurring at the metabolic level in stored iPCs. Understanding better the role of antioxidants such as urate in ex vivo PCs would definitively provide new insights to ameliorate the storage conditions and preserve the functionality of platelets.