Differential expression analysis by RNA-Seq reveals perturbations in the platelet mRNA transcriptome triggered by pathogen reduction systems

Pathogen reduction (PR) systems are used for prevention of infectious agents in blood components such as platelets, but have also shown to increase bleeding in some clinical studies. PR cross-link and damage nucleic acids of pathogens. Here, we show that Intercept (amotosalen + ultraviolet-A [UVA] light) significantly alter the platelet transcriptome. We used the RNA-Seq approach and analyzed transcriptomes of five platelet groups. We found that platelets treated with Intercept significantly changed the expression of more than 1000 genes (p<0.05) relative to the untreated, control platelets. In contrast, platelets treated with the Mirasol PR system (riboflavin + UVB light), or subjected to gamma-irradiation did not show these effects. A cluster of more than 170 mRNAs were identified that were differentially expressed at P<0.001. A vast majority of these transcripts were down-regulated at >2 folds. We also found the SSP+ additive solution present in Intercept constitutes a partial, though small, effect on the platelet transcriptome. We conclude that Intercept significantly affects and interferes the platelet transcriptome, a finding that coincides with previously reported studies showing that Intercept induces platelet activation, impaired platelet aggregation, reduced platelet mean volume, increased release of platelet microparticles and down-regulation of microRNAs in platelets.