The Impact of the Fibrinolytic System on the Risk of Venous and Arterial Thrombosis

Abstract

In this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, alpha2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibrinolytic proteins, including roles in inflammation, vascular remodeling, atherosclerosis, and the metabolic syndrome. The nonfibrinolytic properties of these proteins may have opposing effects on development of arterial disease as compared with the lytic properties, which may explain opposite results in different studies with slightly different population characteristics. These properties may be more relevant in arterial than in venous thrombosis.

Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men

“…30,32 These inconsistent results have been ascribed to the adjustments made for confounders in the analyses because these vary across studies. 4,6 In the ECAT study, the prognostic value of t-PA and PAI-1 was studied after adjustment for clusters of confounding variables. 4 Our results on t-PA and PAI-1 are to a large extent in agreement with that study.…”

“…Besides differences in statistical models used, the roles of the fibrinolytic proteins other than in clot dissolution may also have attributed to the inconsistency of results of different studies (reviewed in Meltzer et al 6 ). Besides its role in clot lysis, plasminogen possibly contributes to destabilization of atherosclerotic plaques independent of fibrin proteolysis.…”

“…However, whether increased levels of t-PA and PAI-1 independently increase the risk remained to be elucidated. 6 PAI-1 is now recognized as a true component of the metabolic syndrome, 7 which is strongly associated with arterial thrombosis. In several studies the predictive value of PAI-1 and t-PA disappeared after adjusting for cardiovascular risk factors such as body mass index (BMI), insulin resistance, inflammation, and lipid levels (reviewed in Meltzer et al 6 ).…”

“…6 PAI-1 is now recognized as a true component of the metabolic syndrome, 7 which is strongly associated with arterial thrombosis. In several studies the predictive value of PAI-1 and t-PA disappeared after adjusting for cardiovascular risk factors such as body mass index (BMI), insulin resistance, inflammation, and lipid levels (reviewed in Meltzer et al 6 ). This may indicate that levels of these fibrinolytic factors are rather a reflection of underlying disease than a direct cause of arterial thrombosis.…”

The overview of brinolysis system contemporary concepts and of its disorders diagnostic methods

“…При измерении уровня ТПА фиксируется, как пра-вило, неактивный комплекс с ПАИ-1, поэтому повы-шенный уровень такого ТПА может характеризовать не повышение активности фибринолиза, а наоборот, его ингибирование [40]. В некоторых лабораториях проводят фибринолитический тест венозной окклю-зии с помощью манжеты: пациенту на руку надева-ют манжету для измерения давления; на 10-20 мин нагнетается давление -среднее между систоличе-ским и диастолическим (но < 100 мм рт.…”