**2. Haemostasis**

#### **2.1 The crosstalk between coagulation cascade and fibrinolytic system**

Knowledge of the universal sequence of events in haemostasis can give vital information to the progress and development of thrombosis [4]. Within the blood coagulation cascade, the extrinsic pathway is mostly activated by vascular endothelial injury. In contrast, the intrinsic pathway is triggered solely through Factor XII (FXII) exposure on the thrombogenic surface. Even though separated, these pathways are interconnected at several points [4]. Both extrinsic and intrinsic pathways are linked to initiating the common pathway, which terminates at the formation of fibrin clots that are subsequently degraded by plasmin during fibrinolysis (**Figure 1**) [5]. Within the damaged endothelium, platelet adhesion and activation are promoted by the extremely exposed thrombogenic subendothelial extracellular matrix (ECM). Through its interactions with proconvertin (FVII), tissue factor (TF) initiates the coagulation cascade by converting prothrombin to thrombin. During secondary haemostasis, the thrombin generated triggers FN generation, which is converted to an insoluble fibrin plug that formed a fibrin mesh network together with aggregated platelets [4]. These assist to stop the blood flow, thus ensuring "haemostasis" and the final step of the coagulation cascade [6]. At the "thrombus", the circulating blood cells become trapped into the fibrin structure, and fibrin cross-linked is accomplished by Factor XIII activator (FXIIIa), which is promoted by the thrombin, leading to solid structural stability and the initial step of the fibrinolytic system [7].

During the repair process, the generated thrombus is destroyed by plasmin activities, produced by its zymogen plasminogen, tissue-type plasminogen activator (t-PA) or uPA on the fibrin clot [8]. Proteolysis of fibrin generates soluble fibrin degradation products (FDPs). The fibrinolytic system is extremely controlled by a protease enzyme inhibitor known as plasminogen activator inhibitor-1 (PAI-1), synthesised by endothelium, adipose tissue and the liver. The PAI-1 serves as a potent irreversible inhibitor of plasminogen activators, including t-PA and uPA, which convert plasminogen to plasmin, to promote fibrinolysis. The major plasminogen activator is t-PA, which has a high affinity to fibrin. The t-PA is secreted by endothelial cells or synthesised locally following the activation of endothelium by histamine, adrenalin, thrombin, FXa and hypoxia [9].
