Type 2 Diabetes and Fibrinolysis

Abstract

Type 2 diabetes (DM2) is associated with complex hemostasis disorders characterised with enhanced coagulation, platelet dysfunction and hypofibrinolysis. These pathological conditions predispose type 2 diabetics towards increased morbidity and mortality due to thrombotic complications. In fact, DM2 is considered the most frequent acquired thrombophilic state. Under physiological conditions, fibrinolytic system is responsible for the lysis of fibrin clot, thus maintaining the blood fluidity. It was first described by Astrup in 1956. The most important molecule in fibrinolytic system is plasmin, which cleaves fibrin clot. It is released in its inactive form called plasminogen from the liver to the blood stream and gets activated by tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), clotting factor XII (FXII) and kallikrein. Plasmin deactivation occurs via several molecules. The best known and most important is ┙2-plasmin inhibitor (┙-2PI). Another one, which was described in early nineteen nineties, is called thrombin-activatable fibrinolysis inhibitor (TAFI). Plasminogen activation and thus plasmin formation is inhibited by plasminogen activator inhibitor type 1 (PAI-1), PAI-2 and PAI-3. Fibrinolysis disorder due to disequilibrium between plasminogen activators and its inhibitors is the most characteristic feature of prothrombotic state associated with diabetes. The fibrinolytic activity in DM2 is influenced by numerous factors, the most crucial ones are glycaemic control, insulinaemia, blood lipid profile, blood pressure, genetic factors and different sorts of medication (Brummel-Ziedins et al., 2009, Alzahrani & Ajjan, 2010a).