The role of fibrinolytic factors in ischaemia

The fibrinolytic system is an enzymatic cascade system whose activation leads to formation of a trypsin-like serine protease, plasmin, which splits insoluble fibrin into soluble degradation products. It is believed that the main function of fibrinolysis is defence against thrombotic occlusion of vessels and dissolution of thrombi once they are formed (thrombolysis). The authors review the recent literature providing evidence that fibrinolysis plays a role in the pathogenesis of vascular occlusions. From earlier studies based on global assay methods it is known that fibrinolysis is depressed in patients with vascular occlusions. Selective assay methods show that almost invariably the fibrinolytic activity of these patients is depressed either following increased levels of fibrinolytic inhibitors (mainly plasminogen activator inhibitor 1 or PAI-1) and/or decreased levels of a plasminogen activator (tissue plasminogen activator or t-PA). In a few cases the molecule of plasminogen shows a conformational abnormality making it less susceptible to conversion to plasmin. In the last decade numerous studies have been published showing a connection between a depressed fibrinolysis and venous thrombosis. In patients with coronary artery occlusion fibrinolysis is depressed mainly because of increased levels of PAI-1. Hypertriglyceridaemia seems to aggravate the defective fibrinolysis. There is also evidence of a decreased fibrinolysis in patients with peripheral ischaemic diseases. A depressed fibrinolysis has also been documented in states predisposing to vascular occlusions. Thus two levels of t-PA/increased levels of PAI-1 have been found in obesity, diabetes mellitus, postoperative states, SLE, malignancies, and miscellaneous diseases often complicated with thrombosis such as Behçet's syndrome. In pregnancy fibrinolysis is depressed because of the presence in blood of PIA-2, an inhibitor of plasminogen activators secreted by the placenta.