Figure 1.

Illustration demonstrating the determinants of endogenous fibrinolysis. (1) High shear/shear gradient results in platelet activation and unravelling of vWF, exposing A-domains for platelet and extracellular matrix binding. This further enhances the affinity of GPIIb/IIIa for fibrinogen. (2) High shear flow contributes to the strength of attachment to the vessel wall. (3) NETs augment coagulation and inhibit fibrinolysis. (4) Platelet-rich clots augment thrombin generation and release of inhibitors including TAFI and PAI-1. This results in densely packed, thin fibrin strands, which are resistant to fibrinolysis. (5) Factor XIIIa-mediated crosslinking of ⍺2-antiplasmin, TAFI and PAI-1 with fibrin inhibits fibrinolysis. (6) Myosin-mediated clot retraction results in increased fibrin density and reduced clot permeability.