血液净化相关性凝血/血栓形成的机制研究相对薄弱，制约了血液净化抗凝技术发展。基于接触激活凝血途径、凝血酶与血小板的最新研究进展，我们提出“FⅡa-polyP-FⅫ级联反应助推凝血酶过量生成导致滤器局部血栓形成”假说。本课题组前期采用新兴膜改性技术，成功构建了阿加曲班抗凝改性膜滤器（AG滤器），对高危出血患者血液净化抗凝进行一种全新探索。本项目以绵羊和人体为研究对象，采用FⅡa（激活血小板），TFPI（抑制启动阶段的凝血酶生成）及特异性拮抗剂SCH79797、UHRA9（阻断polyP-FⅫ途径）等干预，运用CAT、TEG、FCM等方法，观察普通血液净化滤器与AG滤器对血小板活化、多聚磷酸盐（polyP）释放的影响，解析FⅡa-polyP-FⅫ级联反应在血栓形成过程中的作用。本项目将从新的视角阐明血液净化相关性凝血/血栓形成及AG滤器抗凝/抗栓机制，并为促进AG滤器临床转化提供依据。

The fundamental research on the mechanism of blood purification related coagulation/thrombosis is a weak link, restricting the development of anticoagulation techniques during blood purification. Based on the recent advances in the field of contact activation coagulation pathway, thrombin and platelets, we proposed a hypothesis—FⅡa-polyP-FⅫ cascade boosting thrombin overproduction leads to local thrombosis in dialyzer. In our previous research, we have successfully constructed the Argatroban-modified Anticoagulation Dialyzer (the AG Dialyzer) by adopting the emerging technique of membrane modification, which is a new exploration of anticoagulation mode during blood purification in high risk bleeding patients. In this project, we will choose sheep and human as study object, use interventions such as FⅡa (activating platelets), TFPI (inhibiting thrombin generation at the startup of coagulation), specific antagonists SCH79797 and UHRA9 (blocking the polyP-FⅫ pathway), and adopt experimental methods such as CAT, TEG, FCM, so then, we can investigate the effect on platelet activation and polyP release by normal dialyzer and the AG Dialyzer, thus analyzing the role of FⅡa-polyP-FⅫ cascade in the process of thrombosis during blood purification. This project aims to expound the mechanism of blood purification related coagulation/thrombosis and anticoagulation/ antithrombosis of the AG Dialyzer from a completely new perspective, and as well as providing scientific basis for the clinical translation of the AG Dialyzer.