The Pivotal Role of the Endothelium in Haemostasis and Thrombosis

The endothelium plays a pivotal role in the regulation of the haemostatic balance. The function of endothelial cells exceeds far beyond providing a non-thrombogenic inner layer of the vascular wall which maintains the blood fluidity. In physiological circumstances endothelial cells carefully prevent thrombosis by different anticoagulant and antiplatelet mechanisms. Endothelial cells are involved in all major haemostatic pathways upon vascular injury and limit clot formation to the areas where haemostasis is needed to restore vascular integrity. Failure of this complex balance between pro- and anticoagulant systems because of genetic or acquired disturbances may result in bleeding or thrombosis. Endothelial heterogeneity assures adequate homeostasis in the different organs and parts of the vascular tree. The local environment induces heterogeneous endothelial cell phenotypes determined by local needs. This heterogeneity also explains the diverse pathological responses upon disturbed vascular integrity. Localised manifestation of thrombosis in spite of systemic procoagulant disturbances depends on vascular bed-specific properties. Endothelial dysfunction not only precedes atherogenesis but may also predispose to arterial thrombosis. The potential role of the endothelium in venous thrombosis with and without overt vessel wall injury is discussed. The vast majority of endothelial cells are located in the microvessels. Therefore, it is no surprise that endothelial cells play a key role in microcirculatory diseases such as thrombotic microangiopathies and diffuse intravascular coagulation. Microcirculatory endothelial cell activation is an important feature in all thrombotic microangiopathies. In diffuse intravascular coagulation, the endothelium is the interface between inflammation and inappropriate activation of the coagulation system.