Nitric oxide, NO, has been explored as a therapeutic agent to treat thrombosis. In particular, NO has potential in treating mechanical device-associated thrombosis due to its ability to reduce platelet activation and due to the central role of platelet activation and adhesion in device thrombosis. Nitrite is a unique NO donor that reduces platelet activation in that it’s activity requires the presence of red blood cells whereas NO activity of other NO donors is blunted by red blood cells. Interestingly, we have previously shown that red blood cell mediated inhibition of platelet activation by adenosine diphosophate (ADP) is dramatically enhanced by illumination with far-red light that is likely due to photolysis of red cell surface bound NO congeners.

We now report the effects of nitrite, far-red light, and their combination on several measure of blood coagulation using a variety of agonists. We employed turbidity assays in platelet rich plasma, platelet activation using flow cytometry analysis of a fluorescently labeled antibody to the activated platelet fibrinogen binding site, multiplate impedance-based platelet aggregometry, and assessment of platelet adhesion to collagen coated flow-through microslides. In all cases, the combination of far-red light and nitrite treatment decreased measures of coagulation, but in some cases mono-treatment with nitrite or light alone had no effect. Perhaps most relevant to device thrombosis, we observed that platelet adhesions was inhibited by the combination of nitrite and light treatment while nitrite alone and far-red light alone trended to decrease adhesion, but the results were mixed.

These results support the potential of combined far-red light and nitrite treatment for preventing thrombosis in extra-corporeal or shallow-tissue depth devices where the far-red light can penetrate. Such a combined treatment could be advantageous due to the localized treatment afforded by far-red light illumination with minimal systemic effects. Given the role of thrombosis in COVID 19, application to treatment of patients infected with SARS Cov-2 might also be considered.

一氧化氮 (NO) 已被探索作为治疗血栓形成的治疗剂。特别是，NO 在治疗机械装置相关血栓形成方面具有潜力，因为它能够减少血小板活化，并且由于血小板活化和粘附在装置血栓形成中的核心作用。亚硝酸盐是一种独特的一氧化氮供体，可减少血小板活化，因为它的活性需要红细胞的存在，而其他一氧化氮供体的一氧化氮活性会被红细胞减弱。有趣的是，我们之前已经表明，二磷酸腺苷（ADP）介导的红细胞介导的血小板活化抑制作用在远红光照射下显着增强，这可能是由于红细胞表面结合的NO同系物的光解作用。

我们现在报告亚硝酸盐、远红光及其组合对使用各种激动剂的几种凝血测量的影响。我们在富含血小板的血浆中进行了浊度测定，使用流式细胞仪对活化的血小板纤维蛋白原结合位点的荧光标记抗体进行血小板活化分析，基于多板阻抗的血小板聚集度测定，以及评估血小板对胶原包被的流通式显微载玻片的粘附力。在所有情况下，远红光和亚硝酸盐处理的组合都会降低凝血指标，但在某些情况下，仅用亚硝酸盐或光进行单一处理没有效果。也许与装置血栓形成最相关的是，我们观察到亚硝酸盐和光处理的组合抑制了血小板粘附，而单独亚硝酸盐和单独远红光则倾向于降低粘附力，但结果好坏参半。

这些结果支持远红光和亚硝酸盐联合治疗在远红光可以穿透的体外或浅组织深度装置中预防血栓形成的潜力。这种组合治疗可能是有利的，因为远红光照明提供的局部治疗具有最小的全身效应。鉴于血栓形成在 COVID 19 中的作用，也可以考虑应用于治疗感染 SARS Cov-2 的患者。