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Fig. 2 | Thrombosis Journal

Fig. 2

From: Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease

Fig. 2

Three different paths of thrombogenesis that can occur within normal hemostasis. (Reproduced and updated with permission from Chang JC. Blood Coagul Fibrinoplysis. 2018; 29:573–84). Two different thrombotic paths, microthrombotic (ULVWF) and fibrinogenic (TF), are initiated in normal hemostasis, but later the two paths must unify to conclude normal hemostasis with passive role of NETs; it stops the bleeding in external bodily injury and produce the thrombosis in intravascular injury. However, in the different level (depth) of intravascular injury, thrombogenesis takes two different paths. If the level of intravascular injury is confined to the endothelium, lone ULVWF path become activated and causes microthrombosis (i.e., VMTD) because TF path is not activated. On the other hand, if the level of intravascular injury extends from the endothelium to SET/EVT, TF path becomes also activated and causes macrothrombosis (e.g., DVT). In one theoretical situation, if only SET/EVT is injured, available TF is supposed to activate TF path, but in reality this injury does not cause thrombosis without breached endothelium. However, in pathologic hemostasis, aberrant TF activation occurs and produces fibrin clots (i.e., true DIC) in APL due to TF expression in intravascular space from leukemic promyelocytes. APL is a consumption coagulopathy due to lone activation of TF path. This logic is based on “two-path unifying theory”. Please see Figure 2, showing 3 different thrombosis disorders via microthrombogenesis, fibrinogenesis, macrothrombogenesis, which are annotated in bold face. Each thrombognesis occurs when ULVWF path, TF path or combined paths are activated depending upon the levels of damage in intravascular injury (endothelium and SET/EVT). The characters of microthrombi, fibrin clots and macrothrombus from different paths are very different and produce distinctly different clinical thrombotic disorders [20]. Abbreviations: APL acute promyelocytic leukemia, DIC disseminated intravascular coagulation, DVT deep vein thrombosis, EVT extravascular tissue, NET neutrophil extracellular traps, SET subendothelial tissue, TF tissue factor, ULVWF unusually large von Willebrand factor multimers, VMTD vascular microthrombotic disease

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