Endogenous Fibrinolysis

Abstract

Most acute cardiovascular events are attributable to arterial thrombosis. Plaque rupture or erosion stimulates platelet activation, aggregation, and thrombosis, whilst simultaneously activating enzymatic processes that mediate endogenous fibrinolysis to physiologically maintain vessel patency. Interplay between these pathways determines clinical outcome. If proaggregatory factors predominate, the thrombus may propagate, leading to vessel occlusion. However, if balanced by a healthy fibrinolytic system, thrombosis may not occur or cause lasting occlusion. Despite abundant evidence for the fibrinolytic system regulating thrombosis, it has been overlooked compared with platelet reactivity, partly due to a lack of techniques to measure it. We evaluate evidence for endogenous fibrinolysis in arterial thrombosis and review tech-niques to assess it, including biomarkers and global assays, such as thromboelastography and the Global Thrombosis Test. Global assays, simultaneously assessing proaggregatory and fibrinolytic pathways, could play a role in risk strati-fication and in identifying impaired fibrinolysis as a potential target for pharmacological modulation. (J Am Coll Cardiol 2015;65:1683–99) © 2015 by the American College of Cardiology Foundation. C ardiovascular disease is the leading cause of morbidity and mortality in developed coun-tries. The common pathological process responsible for the majority of these disorders, in-cluding acute coronary syndrome (ACS) and ischemic stroke, is the development of an occlusive arterial thrombus.