Fig. 1

Endothelial molecular pathogenesis of “DIC” (EA-VMTD). The molecular events of “DIC”, which is endotheliopathy-associated VMTD (i.e., TTP-like syndrome) with many associated clinical organ syndromes, can be explained by expanded ULVWF path as illustrated in the following “two-activation theory of the endothelium”. For example, in sepsis complement activation occurs and attacks pathogen as a part of innate immune response. In addition to lysis of pathogen by the terminal product C5b-9, it also may induce ECs damage and endothelial dysfunction to the host if endothelial membrane is unprotected by CD59. Endotheliopathy mediates both inflammatory pathway and microthrombotic pathway. Activated inflammatory pathway promotes inflammation and activated microthrombotic pathway triggers microthrombogenesis leading to EA-VMTD if ADAMTS13 is insufficient due to unbalanced excess of ULVWF from endothelial exocytosis or due to partial ADAMTS13 deficiency from heterozygous gene mutation of ADAMTS13 gene. EA-VMTD orchestrates thrombocytopenia, MAHA, and MODS, which are the clinical features of TTP-like syndrome/“DIC”. Abbreviations: AI, adrenal insufficiency; ALF, acute liver failure; ANP, acute necrotizing pancreatitis; ARDS, acute respiratory distress syndrome; ARF, acute renal failure; “DIC”, false disseminated intravascular coagulation; DES, diffuse encephalopathic stroke; DMI, diffuse myocardial infarction; EA-VMTD, endotheliopathy-associated VMTD; DIT, disseminated intravascular microthrombosis; ECs, endothelial cells; FHF, fulminant hepatic failure; HELLPs, hemolysis - elevated liver enzymes - low platelet syndrome; MAHA, microangiopathic hemolytic anemia; SIRS, systemic inflammatory response syndrome; MODS, multiorgan dysfunction syndrome; SS, septic shock; TTP, thrombotic thrombocytopenic purpura; ULVWF, unusually large von Willebrand factor multimers