Influence of fibrinolitic potential reduction in ischemic brain disease development

Abstract

Vascular brain disease are the third leading cause of morbidity and mortality today. Among them ischemic brain disease caused mostly by cerebral atherosclerosis makes almost 80%. The main risk factors for this disease are arterial hypertension, dislipoproteinemia and diabetes but, recently hemostatic system disorders have also been underlined, especially fibrinolytic disorders. PHYSIOLOGY OFFIBRINOLYSIS: The primary role of fibrinolytic system is to make blood vessels passable by prevention of thromb forming or by removing the existing ones. This role is enabled by constant dynamic balance between activators and inhibitors of fibrinolysis. The leading activators are tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA) and the most important inhibitors are 2-antiplasmin, plasminogen activator inhibitor 1 (PAI-1) and thrombin activated fibrinolytic inhibitor (TAFI). In patients with atherosclerosis there is clear insufficiency of fibrinolysis caused mainly by the increased activity of fibrinolytic inhibitors. There is evidence that the level of PAI-1 connected to fibrin directly affects thromb resistance to fibrinolysis and that velocity of thromb lysis in vitro predominantly depends on TAFI concentration. Factor XIII also has influence on thromb structure and stability and Lp(a) lipoprotein is one more factor that is responsible for resistence of thromb to fibrinolysis. Reduced fibrinolytic capacity is noticed in patients with ischemic brain disease resulting from the increased PAI-1 activity. Higher risk for ischemic brain disease is veryfied among people with 4G/4G PAI-1 genotype. Raised level of t-PA anti-gene can also induce reduction of endogenous fibrinolysis. In conclusion we want to underline that a possible pathophysiological significance of fibrinolytic system is assumed in a high percentage of patients with ischemic brain disease. Because of that we need further investigations to establish precise role of fibrinolytic mechanisms in genesis of this disease.