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Original Article

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function

, , , , , , , , & show all
Pages 154-163 | Received 15 Oct 2013, Accepted 17 Feb 2014, Published online: 21 Apr 2014
 

Abstract

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established.

Acknowledgements

We thank Anna Pfister and Anette Schleifer for technical assistance, Achim Jung for the preparation of the samples and Susanne Seifert-Hitzler for logistic support.

Declaration of interest

B. L. was supported by a PhD studentship from the Canadian Blood Services. This work was supported by Grant nos. LIO-202231 and LIO-203061 from the County Council of Östergötland, Sweden (to A. O.) and Grant no. 286777 from the Canadian Blood Services/Canadian Institutes of Health Research (CIHR) Blood Utilization and Conservation Initiative via Health Canada (to P. P.). The views expressed herein do not necessarily represent the view of the federal government. There was no involvement of a pharmaceutical/other company in funding this study. The authors declare that they have no conflicts of interest.

Authorship contributions

A. O., W. E. H., E. C. V., and P. P. conceived and coordinated the study; A. O., W. E. H. and P. P. designed and planned the experiments; W. E. H. coordinated the sampling and treatment of the platelet concentrates; A. O., C. U. M., P. L., A. C., B. L., and P. H. performed the experiments; E. B. provided new analytical tools and expertise; A. O. and E. C. V. performed the statistical analyses; all authors analyzed the data and edited/commented on the manuscript; A. O., W. E. H., E. V. C., and P. P. wrote the manuscript.