Satpathy Chhabi, Mishra Trinath Kumar, Jha Anshu Kumar
Department of Cardiology, MKCG Medical College and Hospital, Berhampur, Odisha, India.
Department of Cardiology, MKCG Medical College and Hospital, Berhampur, Odisha, India.
Indian Heart J. 2025 Mar-Apr;77(2):122-129. doi: 10.1016/j.ihj.2025.02.007. Epub 2025 Feb 25.
The history of coagulation cascade dates back to 17th century. The extrinsic and intrinsic pathways were proposed in 1998. Extrinsic pathway includes the tissue factor and stable factor which activates factor X and with help of factor V, this converts prothrombin to thrombin which is stabilised by factor XIII. This helps to seal the bleeding vessel and is a physiological process as there is only "limited" production of thrombin which doe not expand beyond the damaged site due to absence of tissue factor. On the other hand intrinsic pathway is activated by polyanions, neutrophilic extracellular traps which are present during infection and inflammation. These activate factor XI which activates factor X with the help of factor IX and VIII and then the common pathway ensues. But newer discoveries have shown that this is a very simplified way of explaining the coagulation system. The researches propose that haemostasis is divided into initiation, amplification and propagation phase. Also, the factor VII-tissue factor complex formed activates factor IX and leads to sustained thrombin production as the amount of thrombin produced by extrinsic pathway alone is not sufficient to form a haemostatic plug. Thrombin also activates factor XI and lead to self perpetuation of intrinsic pathway. All the anticoagulants have an inherent property of bleeding. So the newer factor XI and XII inhibitors focus to inhibit the excessive thrombin production without hampering the physiological haemostasis process. This is supported by the fact that congenital factor XI and XII deficiency does not cause excessive bleeding but increased levels did make patients more vulnerable to thromboembolism. This review shall focus on the various factor XI and XII inhibitors which are in the pipeline.
凝血级联反应的历史可以追溯到17世纪。1998年提出了外源性和内源性途径。外源性途径包括组织因子和稳定因子，稳定因子激活因子X，在因子V的帮助下，将凝血酶原转化为凝血酶，凝血酶原由因子XIII稳定。这有助于封闭出血血管，是一个生理过程，因为只有“有限”的凝血酶产生，由于没有组织因子，凝血酶不会扩散到受损部位之外。另一方面，内源性途径由多阴离子、感染和炎症期间存在的中性粒细胞胞外陷阱激活。这些激活因子XI，因子XI在因子IX和VIII的帮助下激活因子X，然后进入共同途径。但新的发现表明，这是一种非常简化的解释凝血系统的方式。研究提出止血分为启动、放大和传播阶段。此外，形成的因子VII-组织因子复合物激活因子IX，并导致持续的凝血酶产生，因为仅外源性途径产生的凝血酶量不足以形成止血栓。凝血酶还激活因子XI，并导致内源性途径的自我延续。所有抗凝剂都有出血的固有特性。因此，新的因子XI和XII抑制剂致力于抑制过量的凝血酶产生，而不影响生理止血过程。先天性因子XI和XII缺乏不会导致过度出血，但水平升高确实会使患者更容易发生血栓栓塞，这一事实支持了这一点。本综述将重点关注正在研发的各种因子XI和XII抑制剂。
