Figure 5.

Pathogenesis of venous combined micro-macrothrombosis (Reproduced and modified with permission from Chang JC. Vasc Health Risk Manag. 2021, 17, 273–298) [4]. The Figure is self-explanatory. The pathogenesis of venous combined micro-macrothrombotic syndrome is the same as in arterial combined micro-macrothrombotic syndrome. Both are combined diseases of the underlying EA-VMTD caused by endotheliopathy occurring in sepsis or other illnesses and additional vascular injury caused by in-hospital vascular accesses. However, their clinical phenotypes are very different. In the venous system of sepsis, vEA-VMTD exists as “silent” microthrombi (e.g., ITP-like syndrome) and additional vascular injury produces fibrin meshes (fibrin clots). However, physiologically “silent” microthrombi and fibrin meshes can unify together via macrothrombogenesis and produce the clinical phenotype of proximal/central DVT (i.e., VTE). In the arterial system with different circulatory hemodynamic (i.e., shear stress flow) and physiologic function (i.e., oxygen delivery), “microangiopathic” microthrombi interact fibrin meshes and unify together via macrothrombogenesis at the multiple small arteries. It produces the clinical phenotype of multiple peripheral gangrene. These characteristic differences create “peripheral gangrene” in arterial system and “VTE” in the venous system even though both are the same combined micro-macrothrombosis as delineated in Table 6. Abbreviations: CVST, cerebral venous sinus thrombosis; DVT, deep venous thrombosis; ECs, endothelial cells; EVT, extravascular tissue; ITP, immune thrombocytopenic purpura; IVCT, inferior vena cava thrombosis; MMT, micro-macrothrombosis; MODS, multiorgan dysfunction syndrome; SET, subendothelial tissue; SVCT, superior vena cava thrombosis; SVT, splanchnic venous thrombosis; TF, tissue factor; ULVWF, ultra large von Willebrand factor; vEA-VMTD venous endotheliopathy-associated vascular microthrombotic disease; VTE, venous thromboembolism.