Van Aelst B, Feys H B, Devloo R, Vanhoorelbeke K, Vandekerckhove P, Compernolle V
Transfusion Research Center, Belgian Red Cross-Flanders, Ghent, Belgium.
Vox Sang. 2015 May;108(4):328-39. doi: 10.1111/vox.12231. Epub 2014 Dec 30.
Photochemical treatment (PCT) of platelet concentrates using photosensitizers and ultraviolet light illumination reduces the proliferation potential of pathogens by damaging biomolecules.
The impact of riboflavin (RF-PRT)- and amotosalen (AS-PCT)-based pathogen inactivation on platelets was studied using microfluidic flow chambers on immobilized collagen using standard platelet concentrates prepared from buffy coats in additive solution. Flow cytometry, metabolic parameters and light transmission aggregometry with thrombin-related peptide, collagen and ristocetin were determined concurrently.
Both PCTs significantly decreased the platelet surface coverage kinetics in flow chambers over the course of the 7-day study. Platelet aggregation was affected following RF-PRT in response to all agonists, while AS-PCT mainly impacted low-dose ristocetin agglutination. RF-PRT induces premature platelet activation because integrin αII b β3 was spontaneously activated, and α-degranulation, phosphatidylserine/-ethanolamine exposure and anaerobic metabolism significantly increased following treatment, which was not the case for AS-PCT. On the other hand, AS-PCT significantly diminished thrombus growth onto von Willebrand factor under shear flow. This defect was caused by fewer integrin αII b β3 interactions, not by defective GPIbα-VWF binding as shown by adhesion experiments in the presence of tirofiban. Moreover, integrin αII b β3 activation was also affected following the activation of platelets via GPVI-FcγRIIa or PAR1. Finally, amotosalen illumination as such is sufficient to induce platelet damage, with no additional measurable effect of the chemical adsorption step. Gamma irradiation caused no significant difference compared to controls on any time-point or for any parameter.
Both PCTs significantly reduce thrombus formation rate but by different biochemical mechanisms.
使用光敏剂和紫外线照射对血小板浓缩物进行光化学处理（PCT），通过破坏生物分子来降低病原体的增殖潜力。
使用微流控流动腔，在固定化胶原蛋白上，采用由添加剂溶液中的白膜制备的标准血小板浓缩物，研究基于核黄素（RF-PRT）和阿莫沙林（AS-PCT）的病原体灭活对血小板的影响。同时测定流式细胞术、代谢参数以及与凝血酶相关肽、胶原蛋白和瑞斯托菌素相关的透光聚集法。
在为期7天的研究过程中，两种PCT均显著降低了流动腔中血小板表面覆盖动力学。RF-PRT处理后，血小板对所有激动剂的聚集均受到影响，而AS-PCT主要影响低剂量瑞斯托菌素凝集。RF-PRT诱导血小板过早激活，因为整合素αIIbβ3自发激活，且处理后α-颗粒释放、磷脂酰丝氨酸/乙醇胺暴露和无氧代谢显著增加，而AS-PCT并非如此。另一方面，AS-PCT显著减少了剪切流作用下血栓在血管性血友病因子上的生长。这种缺陷是由较少的整合素αIIbβ3相互作用引起的，而非如替罗非班存在时的粘附实验所示的GPIbα-VWF结合缺陷。此外，通过GPVI-FcγRIIa或PAR1激活血小板后，整合素αIIbβ3的激活也受到影响。最后，仅阿莫沙林光照就足以诱导血小板损伤，化学吸附步骤无额外可测量的影响。与对照组相比，γ射线照射在任何时间点或任何参数上均无显著差异。
两种PCT均显著降低血栓形成率，但通过不同的生化机制。
