INTERCEPT pathogen reduction of platelet concentrates induces trans-arachidonic acids and affects eicosanoid formation

Abstract

AbstractGamma-irradiation of blood products is mandatory to avoid graft versus host disease in patients with immunosuppressed clinical conditions. Pathogen inactivation techniques were implemented to optimize safe blood component supply. The INTERCEPT treatment uses amotosalen together with UVA irradiation. The functional and molecular implications of these essential treatments have not yet been systematically assessed. The irradiation-induced inactivation of nucleic acids may actually be accompanied with modifications of chemically reactive polyunsaturated fatty acids, known to be important mediators of platelet functions. Thus, here we investigated eicosanoids and related fatty acids released upon treatment and during platelet storage for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. In contrast to gamma-irradiation, here we demonstrate that UVA treatment attenuated the formation of ALOX12-products such as 12-HETE and 12-HEPE but induced the formation of trans-arachidonic acids in addition to 11-HETE and HpODEs. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation and clot firmness hardly differed between the two treatment groups. In vitro synthesis of trans-arachidonic acids (trans-AA) out of arachidonic acid in the presence of β-mercaptoethanol suggested that thiol radicals formed by UVA treatment are responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is plausible to assume that trans-AA and other UVA-induced molecules may have specific biological effects on the recipients, which need to be addressed in future studies.Key pointsA previously unrecognized radical mechanisms for the generation of trans-fatty acids by UVA was identifiedIrradiation with UVA was found to immediately affect the generation of polyunsaturated fatty acid oxidation products