Ultraviolet-Based Pathogen Inactivation Systems: Untangling the Molecular Targets Activated in Platelets

Abstract

Transfusions of platelets are an important cornerstone of medicine; however, recipients may be subject to risk of adverse events associated with the potential transmission of pathogens, especially bacteria. Pathogen inactivation (PI) technologies based on ultraviolet illumination have been developed in the last decades to mitigate this risk. This review discusses studies of platelet concentrates treated with the current generation of PI technologies to assess their impact on quality, PI capacity, safety, and clinical efficacy. Improved safety seems to come with the cost of reduced platelet functionality, and hence transfusion efficacy. In order to understand these negative impacts in more detail, several molecular analyses have identified signaling pathways linked to platelet function that are altered by PI. Because some of these biochemical alterations are similar to those seen arising in the context of routine platelet storage lesion development occurring during blood bank storage, we lack a complete picture of the contribution of PI treatment to impaired platelet functionality. A model generated using data from currently available publications places the signaling protein kinase p38 as a central player regulating a variety of mechanisms triggered in platelets by PI systems.

A double‐virally‐inactivated (Intercept–solvent/detergent) human platelet lysate for in vitro expansion of human mesenchymal stromal cells

“…Combining Intercept and S/D in the manufacture of pooled HPL can, at least partially, meet these requirements. On the one hand, the Intercept treatment, as applied to PC for transfusion, has been shown to inactivate, moderately to highly effectively, several known or emerging enveloped viruses, but some retroviruses, like human immunodeficiency virus, are known to exert some resistance as they possess repair mechanisms against UV‐based inactivation treatments . In addition, the transmission of the nonenveloped viruses hepatitis E virus (HEV) and parvovirus B19 (PB19V) has been reported in patients receiving Intercept‐treated PCs, and limited inactivation of these two viruses has been reported in experimental studies of Intercept‐PC .…”

Blood Utilization and Transfusion Reactions in Pediatric Patients Transfused with Conventional or Pathogen Reduced Platelets

“…The INTERCEPT system uses amotosalen (a psoralen) as the photosensitizing agent which, following exposure to ultraviolet (UV)-A light, crosslinks DNA bases. 22 The MIRASOL pathogen-reduced T system uses riboflavin (vitamin B2) and damages nucleic acid bases following UV-A/B light exposure. 22 A third system, Theraflex-UV (Macropharma, Tourcoing, France), uses UV-C light exposure without a photosensitizing agent for pathogen-reduced PLT production and is undergoing a phase III clinical trial in Europe.…”

“…22 The MIRASOL pathogen-reduced T system uses riboflavin (vitamin B2) and damages nucleic acid bases following UV-A/B light exposure. 22 A third system, Theraflex-UV (Macropharma, Tourcoing, France), uses UV-C light exposure without a photosensitizing agent for pathogen-reduced PLT production and is undergoing a phase III clinical trial in Europe. 22 The clinical efficacy and long-term safety of these products has been a major focus throughout their development.…”

Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)

“…Preclinical studies and clinical trials with PRTs conducted in the preceding 18 years have repeatedly demonstrated changes in both in vitro and in vivo variables . These include changes in metabolic variables in treated PLTs, changes in aggregation, and adhesion function and changes in PLT proteomic and metabolomics measurements . Similar results with plasma products have shown reduced coagulation factor levels after treatment .…”