Figure 4.

Genesis of two different DVT based on two-path unifying theory of hemostasis in vivo. Contemporary concept for every DVT is macrothrombosis in the venous system composed of blood clots containing fibrin clots, platelets, and NETs as a result of activation of TF-FVIIa complex-initiated coagulation cascade following vascular injury in the venous system. However, the exact mechanism producing macrothrombosis has not been determined, nor is the composition of macrothrombus proven. The “two-path unifying theory” of hemostasis and “two-activation theory of the endothelium” have been able to provide the exact role of major hemostatic components, including ULVWF, platelets, coagulation factors, and various cellular and molecular traps including NETs, in the vascular system. Based on hemostatic theories, two different phenotypes of DVT can be identified by their different pathogenesis and character of thrombosis. The genesis of distal DVT in Figure 4 (a) and that of proximal/central DVT (i.e., VTE) in Figure 4 (b) are summarized and elaborated in the text. Abbreviations: DVT, deep venous thrombosis; ECs, endothelial cells; MMT, micro-macrothrombosis; NETS, neutrophil extracellular traps; SET, subendothelial tissue; TF, tissue factor; ULVWF, ultra large von Willebrand factor; vEA-VMTD, venous endotheliopathy-associated vascular microthrombotic disease.