Abstract：
UNASSIGNED: Clinical practice shows that a critical unmet need in the field of thrombosis prevention is the availability of anticoagulant therapy without bleeding risk. Inhibitors against FXIa or FXIIa have been extensively studied because of their low bleeding risk. However, whether these compounds produce synergistic effects has not yet been explored. In this study, analyses of activated partial thromboplastin time in combination with the FXIa inhibitor PN2KPI and the FXIIa inhibitor Infestin4 at different proportions were performed using the SynergyFinder tool identifying synergistic anticoagulation effects. Both an FeCl 3 -induced carotid artery thrombosis mouse model and a transient occlusion of the middle cerebral artery mouse model showed that the combination of PN2KPI and Infestin4, which are 28.57% and 6.25% of the effective dose, respectively, significantly prevents coagulation, and furthermore, dual inhibition does not cause bleeding risk.
摘要：
临床实践表明，预防血栓形成领域的关键未满足需求是无出血风险的抗凝治疗的可用性。已经广泛研究了针对FXIa或FXIIa的抑制剂,因为它们的低出血风险。然而,这些化合物是否产生协同作用尚未被探索。这里,使用SynergyFinder工具对活化的部分凝血活酶时间(aPTT)与不同比例的FXIa抑制剂PN2KPI和FXIIa抑制剂Infestin4进行分析,以确定协同抗凝作用.FeCl3诱导的颈动脉血栓形成小鼠模型和短暂的大脑中动脉闭塞（tMCAO）小鼠模型均显示，PN2KPI和Infestin4的组合有效剂量分别为28.57％和6.25％，分别,显著防止凝血，而且,双重抑制不会引起出血风险。
