Chang Jae C
Department of Medicine, University of California Irvine School of Medicine, Irvine, California, USA.
Blood Coagul Fibrinolysis. 2018 Nov;29(7):585-595. doi: 10.1097/MBC.0000000000000769.
: Hemostasis, endowed to human to protect lives, is a process of logical blood clotting system to prevent blood loss in vascular injury. However, the notion that deadly thrombosis occurs as a result of normal hemostasis in intravascular injury could encounter with conceptual skepticism because the term 'thrombosis' automatically conjures up as serious disease. According to 'two-path unifying theory', normal hemostasis is initiated only by vascular injury through activated unusually large von Willebrand factor (ULVWF) path and/or activated tissue factor (TF) path. When these two equally important paths are unified in normal hemostasis, clotting at external bodily injury site is initiated for wound healing, but in intravascular injury 'blood clots' is formed to produce a disease called 'thrombosis'. As microthrombi from ULVWF path and fibrin clots from TF path become unified, macrothrombus would be formed via thrombogenesis. However, if ULVWF path and TF path cannot be unified due to lone ULVWF path activation, partial hemostasis produces only microthrombi seen in endotheliopathy-associated vascular microthrombotic disease. In real life, in-vivo fibrin clot cannot be formed alone via normal hemostasis because bleeding vascular injury always activates both ULVWF and TF paths. Without vascular injury, microthrombi due to activated ULVWF path occur in ADAMTS13 deficiency in thrombotic thrombocytopenic purpura, and fibrin clots due to activated TF path occur in acute promyelocytic leukemia. These two conditions can be called pathologic hemostasis. Three thrombogenic pathways produce three thrombotic disorders, which include macrothrombosis, microthrombosis and true DIC through macrothrombogenesis, microthrombogenesis and fibrinogenesis in both physiologic and pathological hemostasis.
止血是人体赋予的保护生命的机制，是逻辑化的血液凝固系统防止血管损伤时失血的过程。然而，血管内损伤时正常止血导致致命血栓形成这一观点可能会遭遇概念上的质疑，因为“血栓形成”一词会自动让人联想到严重疾病。根据“双途径统一理论”，正常止血仅通过异常活化的超大血管性血友病因子（ULVWF）途径和/或活化的组织因子（TF）途径由血管损伤引发。当这两条同等重要的途径在正常止血过程中统一时，身体外部损伤部位会启动凝血以促进伤口愈合，但在血管内损伤时会形成“血凝块”从而引发一种名为“血栓形成”的疾病。随着来自ULVWF途径的微血栓和来自TF途径的纤维蛋白凝块合并，会通过血栓形成过程形成大血栓。然而，如果由于单独的ULVWF途径活化导致ULVWF途径和TF途径无法合并，部分止血仅产生见于内皮病相关血管微血栓形成疾病中的微血栓。在现实生活中，正常止血过程无法单独形成体内纤维蛋白凝块，因为出血性血管损伤总会同时激活ULVWF和TF途径。在没有血管损伤的情况下，血栓性血小板减少性紫癜中因ADAMTS13缺乏导致ULVWF途径活化而出现微血栓，急性早幼粒细胞白血病中因TF途径活化出现纤维蛋白凝块。这两种情况可称为病理性止血。三种血栓形成途径产生三种血栓形成性疾病，包括在生理和病理性止血过程中通过大血栓形成、微血栓形成和纤维蛋白形成分别导致的大血栓形成、微血栓形成和真性弥散性血管内凝血。
