## 4 Discussion  
### Physiology of Haemostasis  
The surface of activated platelets is the most important site for the activation of coagulation factors, which results in further platelet activation and the formation of fibrin. In a healthy organism, the normal platelet count in peripheral blood ranges from 150,000 to 450,000/\(\upmu\)L and the half-life of circulating platelets is approximately 7-10 days. The main regulator of platelet production is the thrombopoetin hormone (TPO), whose synthesis occurs in the liver and is increased during inflammation, specifically induced by Interleukin 6. TPO binds to its receptor present on megakaryocytes and platelets, which are removed from the bloodstream. The reduction in megakaryocyte and platelet mass increases the level of TPO, which in turn stimulates the production of platelets [5; 6; 7; 8; 9]. As for the role of the vessel wall, the endothelium is a physiologically active entity that intervenes in the flow of nutrients and biologically active molecules, the control of vascular permeability, the interactions of the figurative elements of the blood with the vascular wall, the inflammatory response, and angiogenesis [10; 11; 12; 13]. Under normal conditions, the endothelium represents an antithrombotic surface, but under stimulation, it rapidly turns towards a prothrombotic function capable of promoting coagulation, inhibiting fibrinolysis, and activating platelets [1; 2]. The normal vascular endothelium contributes to the prevention of thrombosis by inhibiting platelet function. However, when it is damaged, its inhibitory effects are overcome, and the platelets adhere to the exposed subendothelium surface through the Von Willebrand factor (VWD). Platelet adhesion promotes intracellular signals that lead to a conformational change and activation of the membrane platelet receptor glycoprotein IIb/IIIa, followed by fibrinogen or VWF binding and platelet aggregation [1; 2; 3; 4]. Once activated, platelets release the contents of their granules, including nucleotides, adhesion proteins, growth factors, and procoagulant factors, promoting platelet aggregation and clot formation, as well as modifying the environment in which the clot itself forms [1; 2; 3]. During the aggregation phase, more platelets are recruited to the site of damage, resulting in the formation of the occlusive platelet thrombus. Thus, the platelet plug is then stabilized by a fibrin network, which forms simultaneously as a product of the coagulation cascade [1]. The haemostatic process can therefore be summarized in two main phases: primary haemostasis and secondary haemostasis. Primary haemostasis is the formation of the primary platelet thrombus, which depends on vascular integrity and platelet function and the following two physiological mechanisms: (1) vasoconstriction, which reduces blood extravasation and initiates the next phase, favouring platelet adhesion, through the exposure of the collagen fibres of the damaged vessel; (2) exchange of electrical potential [1], assisted by intrinsic factors of the vascular endothelium. In platelet activation, platelets are recruited on the damaged site, adhere to it, and subsequently, with the secretion of platelet factors, aggregation occurs with the formation of the thrombotic plug [2; 3]. In primary haemostasis, in response to a vessel injury, the vessel itself contracts and increases its permeability in response to the release of endothelin. The extracellular matrix exposed by vascular damage attracts circulating platelets, which undergo conformational changes and degranulate, releasing factors such as fibronectin, ADP, and thromboxane. This increases the aggregation capability between one platelet and another and between platelets and the endothelium, leading to the formation of the \"white thrombus\" first (temporary \"plug\") and, eventually, the secondary haemostatic plug [7]. Thereafter, secondary haemostasis, also called the plasma phase, takes place, consisting of the processes of coagulation and fibrinolysis.