Abstract
It has been well established that inherited or acquired hypercoagulability is a risk
factor for venous thrombosis. In addition, hypercoagulability may contribute to the
risk of arterial events. Much less is known regarding the role of the fibrinolytic
system in the risk of thrombotic disease, which partly relates to the lack of validated
assays. A plasma-based global fibrinolysis assay, which is sensitive to plasma levels
of plasminogen, regulators of fibrinolysis, and proteins involved in coagulation,
has been used in large epidemiological studies to assess the role of fibrinolysis
in thrombosis. It has been demonstrated that a hypofibrinolytic state increases the
risk of a first venous thrombosis, but not of a recurrence. This increased risk of
venous thrombosis associated with plasma hypofibrinolysis appears primarily driven
by elevated plasma levels of thrombin-activatable fibrinolysis inhibitor and plasminogen
activator inhibitor type 1. The combination of hypercoagulability and hypofibrinolysis
synergistically enhances the risk of a first venous event. Plasma hypofibrinolysis
may constitute a risk factor for the postthrombotic syndrome. Decreased fibrinolytic
potential is also associated with an increased risk of arterial thrombosis, but only
in individuals younger than 55 years. The association between hypofibrinolysis and
myocardial infarction appears primarily driven by elevated levels of α2 -antiplasmin. Although recent studies have clearly demonstrated a role of the fibrinolytic
system in thrombotic disease, the clinical utility of plasma-based clot lysis assays
is probably limited.
Keywords fibrinolysis - venous thrombosis - arterial thrombosis - myocardial infarction - stroke
