Gravemann U, Handke W, Sumian C, Alvarez I, Reichenberg S, Müller T H, Seltsam A
German Red Cross Blood Service NSTOB, Springe, Germany.
Macopharma S.A., Tourcoing, France.
Vox Sang. 2018 May;113(4):368-377. doi: 10.1111/vox.12643. Epub 2018 Feb 27.
Photodynamic treatment using methylene blue (MB) and visible light is in routine use for pathogen inactivation of human plasma in different countries. Ambient and product temperature conditions for human plasma during production may vary between production sites. The influence of different temperature conditions on virus inactivation capacity and plasma quality of the THERAFLEX MB-Plasma procedure was investigated in this study.
Plasma units equilibrated to 5 ± 2°C, room temperature (22 ± 2°C) or 30 ± 2°C were treated with MB/light and comparatively assessed for the inactivation capacity for three different viruses, concentrations of MB and its photoproducts, activity of various plasma coagulation factors and clotting time.
Reduced solubility of the MB pill was observed at 5 ± 2°C. Photocatalytic degradation of MB increased with increasing temperature, and the greatest formation of photoproducts (mainly azure B) occurred at 30 ± 2°C. Inactivation of suid herpesvirus, bovine viral diarrhoea virus and vesicular stomatitis virus was significantly lower at 5 ± 2°C than at higher temperatures. MB/light treatment affected clotting times and the activity of almost all investigated plasma proteins. Factor VIII (-17·7 ± 8·3%, 22 ± 2°C) and fibrinogen (-14·4 ± 16·4%, 22 ± 2°C) showed the highest decreases in activity. Increasing plasma temperatures resulted in greater changes in clotting time and higher losses of plasma coagulation factor activity.
Temperature conditions for THERAFLEX MB-Plasma treatment must be carefully controlled to assure uniform quality of pathogen-reduced plasma in routine production. Inactivation of cooled plasma is not recommended.
在不同国家，使用亚甲蓝（MB）和可见光进行光动力治疗已常规用于人血浆的病原体灭活。生产过程中，人血浆的环境温度和产品温度条件在不同生产地点可能有所不同。本研究调查了不同温度条件对THERAFLEX MB-血浆程序的病毒灭活能力和血浆质量的影响。
将平衡至5±2°C、室温（22±2°C）或30±2°C的血浆单位用MB/光进行处理，并对三种不同病毒的灭活能力、MB及其光产物的浓度、各种血浆凝血因子的活性和凝血时间进行比较评估。
在5±2°C时观察到MB丸剂的溶解度降低。MB的光催化降解随温度升高而增加，在30±2°C时光产物（主要是天青B）的生成量最大。猪疱疹病毒、牛病毒性腹泻病毒和水疱性口炎病毒在5±2°C时的灭活率明显低于较高温度时。MB/光处理影响凝血时间和几乎所有研究的血浆蛋白的活性。因子VIII（-17.7±8.3%，22±2°C）和纤维蛋白原（-14.4±16.4%，22±2°C）的活性下降幅度最大。血浆温度升高导致凝血时间变化更大，血浆凝血因子活性损失更高。
必须仔细控制THERAFLEX MB-血浆治疗的温度条件，以确保常规生产中经病原体灭活的血浆质量均匀。不建议对冷却后的血浆进行灭活处理。
