Hemostasis

Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma, vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and by the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction (Becker et al. 2000).

The chief trigger for the change in endothelial function that leads to the formation of a haemostatic thrombus is the loss of the endothelial cell barrier between blood and extracellular matrix components (Ruggeri 2002). Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion (Savage & Cattaneo et al. 2001).

Three mechansism contribute to the loss of blood following vessel injury. The vessel constricts, reducing the loss of blood. Platelets adhere to the site of injury, become activated and aggregate with fibrinogen into a soft plug that limits blood loss, a process termed primary hemostasis. Proteins and small molecules are released from granules by activated platelets, stimulating the plug formation process. Fibrinogen from plasma forms bridges between activated platelets. These events initiate the clotting cascade (secondary hemostasis). Negatively-charged phospholipids exposed at the site of injury and on activated platelets interact with tissue factor, leading to a cascade of reactions that culminates with the formation of an insoluble fibrin clot.

血液凝固是一种生理反应，其最终目的是终止受伤血管的出血。在正常情况下，血管内皮细胞支持血管舒张，抑制血小板粘附和活化，抑制凝血，增强纤维蛋白裂解，并具有抗炎特性。在急性血管损伤的情况下，血管收缩机制占主导地位，内皮细胞呈现出促血栓形成、促凝血和促炎症的性质。这一变化是通过减少内皮细胞舒张剂：腺苷、NO和前列环素；以及通过ADP、血清素和血栓素直接作用于血管平滑肌细胞，引发其收缩（Becker et al. 2000）来实现的。导致形成止血血栓的内皮功能改变的主要触发因素是内皮细胞屏障在血液与细胞外基质成分之间的丧失（Ruggeri 2002）。循环中的血小板识别并区分内皮损伤区域；在此，它们粘附于暴露的亚内皮层。它们与各种血栓生成底物以及局部生成或释放的激动剂的相互作用导致血小板活化。这一过程可分为两个阶段：首先，粘附——即最初对表面的牵连，其次，聚集——即血小板之间的粘合（Savage & Cattaneo et al. 2001）。三种机制导致了血管损伤后的出血。血管收缩以减少出血，血小板粘附于损伤部位，活化并与纤维蛋白原聚集形成软塞，限制出血，这一过程被称为初级止血。活化血小板从颗粒中释放蛋白质和小的分子，刺激塞子形成过程。血浆中的纤维蛋白原在活化血小板之间形成桥梁。这些事件启动了凝血级联反应（次级止血）。在损伤部位和活化血小板暴露的带负电荷的磷脂与组织因子相互作用，导致一系列反应，最终形成不溶性的纤维蛋白凝块。