Flow path system of ultraviolet C irradiation from xenon flash to reduce bacteria survival in platelet products containing a platelet additive solution

Abstract

BACKGROUND: Our previous study showed that ultraviolet C (UVC) from xenon (Xe) flash without any photoreactive compounds inactivated bacteria in platelet concentrates (PCs) with less damage to platelets (PLTs) as compared with Xe flash containing ultraviolet A, ultraviolet B, and visible light. Here, we report a UVC irradiation system for PCs under flow conditions consisting of a flow path-irradiation sheet, a peristaltic pump, and a collection bag. STUDY DESIGN AND METHODS: Plateletconcentrates containing Ringerʼs solution (R-PCs) inoculated with bacteria were injected into a flow path sheet using a peristaltic pump, being irradiated with UVC from Xe flash. The quality of the irradiated PCs containing platelet additive solution (PAS-PCs) was assessed based on PC variables, PLT surface markers, and aggregation ability. RESULTS: Streptococcus dysgalactiae (12 tests) andEscherichia coli (11) were all negative on bacterial culture, while Staphylococcus aureus (12) and Klebsiella pneumoniae (14) grew in one and two R-PCs, respectively. Bacillus cereus spores were inactivated in 7 of 12 R-PCs. PC variables became significantly different between irradiated and nonirradiated PAS-PCs. P-selectin, first procaspase-activating compound (PAC-1) binding, and phosphatidylserine increased by irradiation. Aggregability stimulated by adenosine diphosphate, collagen, or thromboxane A 2 increased in the irradiated PAS-PCs, while that by thrombin became smaller compared with nonirradiated controls.CONCLUSION: This newly developed system inactivated bacteria including spores in R-PCs. PAS-PCs irradiated by this system retained acceptable in vitro quality and aggregability. Usage of a peristaltic pump instead of agitator during irradiation may enable this system to be directly combined with an apheresis blood cell separator. E ven in the developed countries, transfusiontransmitted bacterial infection remains a serious lifethreatening adverse event following the transfusion of platelet concentrates (PCs). PC stored at a temperature of 20 to 24°C is susceptible to bacterial growth, although its incidence is quite low. In 2017, a fatal sepsis case caused by the transfusion of a PC contaminated with Escherichia coli was reported to the Japanese Red Cross Blood Service Headquarters, 1 although efforts to eliminate bacterial contamination have been promoted by a combination of improved skin disinfection and the diversion of initial blood flow at blood donation, 2 in addition to a short shelf life of PCs (3 days) in Japan.A longer shelf life of PCs (≥5 days) in many countries makes inventory management easier. Automated culture systems, such as BacT/ALERT 3D (BioMérieux), have been widely implemented in those countries for the detection of bacterial contamination in PCs by sampling an aliquot of PCs within ABBREVIATIONS: ADP = adenosine diphosphate; ANOVA = analysis of variance; FDA = US Food and Drug Administration; FITC = fluorescein isothiocyanate; HSR = hypotonic shock response; ihPAS = in-house platelet additive solution; MPV = mean pla...

In vitro thrombus formation and in vivo hemostasis mediated by platelets irradiated with bactericidal ultraviolet C from xenon flash under flow conditions

“…In this study, we investigated the thrombotic and hemostatic ability of PAS‐PCs irradiated with UVC from Xe flash, and found that flash UVC‐irradiated PAS‐PCs are more effective regarding in vitro thrombus formation as well as in vivo hemostasis than nonirradiated PAS‐PCs. However, it should be noted that the current study was performed under irradiation conditions that achieved approximately 2‐log bacterial reduction, as shown in a previous study 7 . On the other hand, commercially available methods, Mirasol and Intercept, achieve more than 4‐log bacterial reduction.…”

“…Recently, we reported a bacteria reduction system using ultraviolet C (UVC) from a xenon (Xe) flash lamp under flow conditions during irradiation. In our previous study, this system achieved approximately 2‐log reduction of bacteria spiked into PLT concentrates with PLT additive solution (PAS‐PCs), and 58% to 100% of PAS‐PCs maintained their sterility depending on bacterial species for 6 days after the treatment 7 . The study also showed that flash UVC‐irradiated PAS‐PCs retained acceptable in vitro quality compared with nonirradiated PAS‐PCs.…”

“…Expression of glycoprotein (GP) Ibα and the conformational change of integrin αIIbβ3 on PLTs were analyzed by flow cytometry with antibodies of phycoerythrin (PE)‐conjugated CD42b (Beckman Coulter, Brea, California) or fluorescein isothiocyanate (FITC)‐conjugated PAC‐1 (Becton Dickinson, San Jose, California), respectively, as previously described 7 . As a negative control, RGDS peptide (Sigma, St. Louis, Missouri), a competitive inhibitor of PAC‐1, was added at a final concentration of 1 mg/mL in addition to PAC‐1.…”

“…PAS‐PCs were irradiated with UVC from Xe flash under flow conditions as previously reported 7 . Briefly, an in‐house fabricated flow sheet (145 × 135 mm, 0.2‐mm thickness) made with a polyolefin culture bag (A‐1000NL, NIPRO, Osaka, Japan) was sandwiched between two U330/250 filters with 0.3‐mm spacers to achieve UVC irradiation (200‐290‐nm wavelength) from Xe flash by excluding ultraviolet A, ultraviolet B, and visible light 10 .…”

UV light-emitting diode (UV-LED) at 265 nm as a potential light source for disinfecting human platelet concentrates

“…In the past decade, efforts have been made to develop a single-step disinfection method for PCs by using a conventional low-pressure mercury UV lamp with an emission wavelength of 254 nm, as it works in the absence of photosensitizers [31,32]. A similar approach with UVC radiation at �270 nm has been proposed in bench-scale experiments [33][34][35] and uses xenon (Xe)-lamp flush through a selective optical bandpass filter for PC disinfection. These methods have some limitations, including safety concerns associated with the use of mercury in lowpressure UV lamps, and the large size and high heat generation associated with Xe-lamps.…”