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Journal Article
Review
Disseminated intravascular coagulation: new identity as endotheliopathy-associated vascular microthrombotic disease based on in vivo hemostasis and endothelial molecular pathogenesis.
Thrombosis Journal 2020
Disseminated intravascular coagulation (DIC) can be correctly redefined as disseminated intravascular microthrombosis based on "two-path unifying theory" of in vivo hemostasis. "DIC" is a form of vascular microthrombotic disease characterized by "microthrombi" composed of platelets and unusually large von Willebrand factor multimers (ULVWF). Microthrombotic disease includes not only "DIC", but also microthrombosis occurring in thrombotic thrombocytopenic purpura (TTP), TTP-like syndrome, and focal, multifocal and localized microthrombosis. Being a hemostatic disease, microthrombotic disease occurs as a result of lone activation of ULVWF path via partial in vivo hemostasis. In endothelial injury associated with critical illnesses such as sepsis, the vascular damage is limited to the endothelial cell and activates ULVWF path. In contrast, in intravascular traumatic injury, the local damage may extend from the endothelial cell to subendothelial tissue and sometimes beyond, and activates both ULVWF and tissue factor (TF) paths. When endotheliopathy triggers exocytosis of ULVWF and recruits platelets, ULVWF path is activated and promotes microthrombogenesis to produce microthrombi composed of microthrombi strings, but when localized vascular damage causes endothelial and subendothelial tissue damage, both ULVWF and TF paths are activated and promote macrothrombogenesis to produce macrothrombus made of complete "blood clots". Currently, "DIC" concept is ascribed to activated TF path leading to fibrin clots. Instead, it should be correctly redefined as microthrombosis caused by activation of ULVWF path, leading to endotheliopathy-associated microthrombosis. The correct term for acute "DIC" is disseminated microthrombosis-associated hepatic coagulopathy, and that for chronic "DIC" is disseminated microthrombosis without hepatic coagulopathy. TTP-like syndrome is hematologic phenotype of endotheliopathy-associated microthrombosis. This correct concept of "DIC" is identified from novel theory of " in vivo hemostasis", which now can solve every mystery associated with "DIC" and other associated thrombotic disorders. Thus, sepsis-associated coagulopathy is not "DIC", but is endotheliopathy-associated vascular microthrombotic disease.
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