2023 FDA Science Forum
Metabolomics Evaluation of the Impact of Violet-Blue Light (405 nm) on Platelet Concentrate
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Contributing OfficeNational Center for Toxicological Research
Abstract
Introduction
Ex vivo stored human platelet concentrates (PCs) are an essential life-saving transfusion product. PCs are susceptible to bacterial contamination during the 5-7 day of storage at 22 ± 2°C in gas permeable bags. Current FDA approved pathogen reduction technologies (PRT) use external photosensitizers in combination with UV light irradiation. Since UV light is harmful to mammalian cells, we have been evaluating violet-blue light to determine whether it can serve as an alternate to PRT technology, without additional exogenous photosensitizers. An LC/MS-based metabolomics analysis was conducted to evaluate the impact of violet-blue light on the platelets (PLTs).
Methods
Apheresis-collected human PCs were uniformly split into two transfer bags from each donor. One PC bag was used as control (no light treatment) and the other bag was used for the light treatment. PLTs in the bags were exposed to 405 nm light at an irradiance of approximately 54 J/cm2 for 1h, and 270 J/cm2 for 5h. The protocol was approved by the FDA Research Involving Human Subjects Committee. LC/MS-based metabolomics analysis was conducted to identify the metabolic changes in both PLTs and plasma.
Preliminary Data
At 5h treatment, the lactate level detected by LC/MS was 1.6-fold increases, which was consistent with the fold change (~1.7 fold) detected by the blood gas analyzer. No changes were observed either in platelet aggregation inhibitory factors, or platelet activation factors. No changes were observed in lysoPCs or PCs, which indicated that the integrity of PLTs was intact after the light exposure. At 5h treatment, the distinctive changes were increases in hydroxy-fatty acids, OH-fatty acyl-carnitines, and aldehydes, indicative of induction of lipid peroxidation. Lower levels of glutathione, vitamin A and uric acid were observed, which might be caused by counteracting the light-induced reactive oxygen species (ROS). Observed increases in endogenous vitamin D-derivative photosensitizers would help enhance the microbicidal potential of the light. In summary, platelet integrity, activation and aggregation potential-impeding biomolecules were unaffected by the light treatment. However, a comprehensive functional analysis of the light-treated platelets in the context of metabolomic changes is warranted to evaluate the potential application of 405 nm light treatment for platelet safety.
