Fig. 2

a Normal hemostasis based on “two-path unifying theory”. (Updated and reproduced with permission from Walters Kluwer Health, Inc., and Chang JC: Blood coagulation Fibrinolysis 2018; 29:573–584). The concept of this theory is derived from physiologic changes associated with the different levels of vascular wall damage in vascular injury as explained in three essentials in normal hemostasis (Table 3). The nature has endowed human with only “one” normal hemostatic system. Hemostasis protects lives from unnecessary bleeding in external bodily injury and aids in self-wound healing. It also warns human to avoid unnecessary self-inflicted injury and hostile environmental insult that can cause intravascular injury leading to deadly thrombotic disorders. This is true irony of nature that exactly same normal hemostasis not only provides wound healing but also can lead to life-threatening thrombosis. As explained in the text, two sub-hemostatic paths (ULVWF and TF) are initiated in vascular injury, which have to be unified to lead to normal blood clotting in external bodily injury and trigger macrothrombus in intravascular injury. In a certain disease (e.g., sepsis), only ULVWF path is activated as seen in “DIC”, and in another disease (e.g., APL), only TF path is activated as seen in true “DIC”. The former produces EA-VMTD and the latter produces fibrin clot disease. If both paths were activated simultaneously in local traumatic vascular injury, the unifying process of two hemostatic paths is called macrothrombogenesis, which produce macrothrombus. These three paths of thrombogeneses are explained in the text [3, 4]. Abbreviations: APL, acute promyelocytic leukemia; “DIC”, false disseminated intravascular coagulation; EA-VMTD, endotheliopathy-associated vascular microthrombotic disease; EVT, extravascular tissue; SET, subendothelial tissue; NETs, neutrophil extracellular traps; TF, tissue factor; ULVWF, unusually large von Willerand factor multimers. b Three paths to thrombogenesis based on “two-path unifying theory”. (Reproduced with permission from Walters Kluwer Health, Inc., and Chang JC: Blood coagulation Fibrinolysis 2018; 29:585–595). Figure 2b illustrates three different thrombogenetic paths in “two-path unifying theory of hemostasis” (microthrombogenesis, fibrinogenesis and macrothrombogenesis) to form respective blood clots. Each pathogenesis occurs when ULVWF path, TF path or combined path is utilized depending upon the levels of vascular wall damage following intravascular injury (ECs, SET, and EVT). The characters of the thrombi/fibrin clots from different paths are very different and produce distinctly different clinical phenotypic thrombotic disorders. In “DIC”, microthrombogenesis occurs due to lone activation of ULVWF path and leads to EA-VMTD, which hematologic phenotype is TTP-likes syndrome. Abbreviations: “DIC”, false disseminated intravascular coagulation; EA-VMTD, endotheliopathy-associated vascular microthrombotic disease; ECs, endothelial cells; EVT, extravascular tissue; SET, subendothelial tissue; NETs, neutrophil extracellular traps; TF, tissue factor; ULVWF, unusually large von Willebrand factor multimers