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

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.

The clinical significance of platelet microparticle-associated microRNAs

“…Therefore, it appears likely that pathogen reduction technologies may enhance the formation of platelet MPs in platelet concentrates. Although this hypothesis remains to be validated, preliminary data support it [57].…”

“…nucleases)/conditions of the extracellular milieu and contribute to the stability of microRNAs outside of cells. Platelets have been shown to release EVs upon activation by physiological agonists/mediators, such as (i) collagen, which mimics the matrix exposed upon damage of the vessel wall, (ii) ADP, which is released from activated platelets, and (iii) thrombin, which is generated during coagulation and is simulated by thrombinreceptor activating peptide (TRAP) [57]. Platelets are also activated by the increased shear stress caused by a reduced lumen at sites of atherosclerotic plaques.…”

“…In addition, we have shown that pathogen reduction technologies, which aim to reduce the risk of transfusiontransmitted infections and are being implemented worldwide, induce platelet activation and a decrease in platelet mRNA [85] and microRNA [57] levels. These changes in RNA levels were concomitant with a reduction in platelet mean volume and an increase in MP concentration in platelet concentrates.…”

Platelet MicroRNAs: An Overview

“…In line with this concept, recently, Osman et al [44] have reported changes in platelet miRNAs associated with different pathogen reduction treatments relative to respective controls, which further suggests that miRNAs of platelets have the potential to be the markers for a given context.…”

Wissenschaftliche Erläuterungen zur Stellungnahme „Bewertung von Apherese- und Pool-Thrombozytenkonzentraten“ des AK Blut vom 31.03.2015

“…Die möglichen Auswirkungen dieser Verfahren auf die Qualität und Wirksamkeit der Thrombozyten sowie im Hinblick auf mögliche Nebenwirkungen der Verfahren bzw. der dabei eingesetzten Stoffe werden wissenschaftlich noch diskutiert [178]. Der AK Blut stellte in seinen Ergän-zungen zum Votum 38 [179] …”