Abstract
The extent and duration of occlusive thrombus formation following an arterial atherothrombotic plaque disruption may be determined by the effectiveness of endogenous fibrinolysis. The determinants of endogenous fibrinolysis are the subject of much research, and it is now broadly accepted that clot composition as well as the environment in which the thrombus was formed play a significant role. Thrombi with a high platelet content demonstrate significant resistance to fibrinolysis, and this may be attributable to an augmented ability for thrombin generation and the release of fibrinolysis inhibitors, resulting in a fibrin-dense, stable thrombus. Additional platelet activators may augment thrombin generation further, and in the case of coronary stenosis, high shear has been shown to strengthen the attachment of the thrombus to the vessel wall. Neutrophil extracellular traps contribute to fibrinolysis resistance. Additionally, platelet-mediated clot retraction, release of Factor XIII and resultant crosslinking with fibrinolysis inhibitors impart structural stability to the thrombus against dislodgment by flow. Further work is needed in this rapidly evolving field, and efforts to mimic the pathophysiological environment in vitro are essential to further elucidate the mechanism of fibrinolysis resistance and in providing models to assess the effects of pharmacotherapy.
Highlights
Atherothrombotic events are a considerable cause of morbidity and mortality
Emerging data suggest that assessment of endogenous fibrinolysis may help, through identifying patients with impaired endogenous fibrinolysis who are at markedly increased risk of ischaemic events [1,2]
Areas of discussion will include the role of thrombin, thrombin generation, high shear-induced platelet activation and clot stabilisation, clot retraction, Factor XIII and neutrophil extracellular traps (NETs)
Summary
Atherothrombotic events are a considerable cause of morbidity and mortality. Much focus and treatment far has surrounded the inhibition of platelets due to their crucial role in arterial thrombus formation. Optimising risk assessment is essential to help identify these patients, with the ultimate aim to reduce events. Emerging data suggest that assessment of endogenous fibrinolysis may help, through identifying patients with impaired endogenous fibrinolysis who are at markedly increased risk of ischaemic events [1,2]. Platelets again seem to be significant modulators of endogenous fibrinolysis, and in this review, we will discuss the mechanisms for mediating resistance to fibrinolysis and the evidence supporting the role of platelets. Areas of discussion will include the role of thrombin, thrombin generation, high shear-induced platelet activation and clot stabilisation, clot retraction, Factor XIII and neutrophil extracellular traps (NETs). (6) Myosin-mediated clot retraction results in increased fibrin density and reduced clot permeability
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
