Metabolomics study of platelet concentrates photochemically treated with amotosalen and UVA light for pathogen inactivation

• Published in: Transfusion (Philadelphia, Pa.) Pa.), 2020-02, Vol.60 (2), p.367-377
• Main Authors: Jóhannsson, Freyr, Árnason, Níels Á., Landrö, Ragna, Guðmundsson, Sveinn, Sigurjonsson, Ólafur E., Rolfsson, Óttar
• Format: Article
• Language: English
• Subjects: Buffy coat; Constraint modelling; Contamination; Deactivation; Dimers; Energy metabolism; Functional groups; Glucose metabolism; Health risks; Hydrophobicity; Inactivation; Intracellular; Mass spectrometry; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Nucleic acids; Nutrient utilization; Pathogens; Platelets; Ultraviolet radiation
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.15610

ABSTRACT BACKGROUND The risk of bacterial contamination and the deterioration of platelet (PLT) quality limit the shelf‐life of platelet concentrates (PCs). The INTERCEPT pathogen inactivation system reduces the risk of pathogen transmission by inhibiting nucleic acid replication using a combination of a photo‐reactive compound and UVA illumination. The goal of this study was to investigate the effects the INTERCEPT system has on the PLT metabolome and metabolic activity. STUDY DESIGN AND METHODS Paired units of buffy coat‐derived PCs were generated using a pool and split strategy (n = 8). The paired PCs were either treated with the INTERCEPT system or left untreated. Samples were collected on Days 1, 2, 4, and 7 of storage. Ultra‐performance chromatography coupled with time‐of‐flight mass spectrometry was used to analyze the extra‐ and intracellular metabolomes. Constraint‐based metabolic modeling was then used to predict the metabolic activity of the stored PLTs. RESULTS A relatively large number of metabolites in the extracellular environment were depleted during the processing steps of the INTERCEPT system, in particular, metabolites with hydrophobic functional groups, including acylcarnitines and lysophosphatidylcholines. In the intracellular environment, alterations in glucose and glycerophospholipid metabolism and decreased levels of 2‐hydroxyglutarate were observed following the INTERCEPT treatment. Untargeted metabolomics analysis revealed residual amotosalen dimers present in the treated PCs. Systems‐level analysis of PLT metabolism indicated that the INTERCEPT system does not have a significant impact on the PLT energy metabolism and nutrient utilization. CONCLUSIONS The INTERCEPT system significantly alters the metabolome of the stored PCs without significantly influencing PLT energy metabolism.