Munkvad S
Department of Clinical Chemistry, Ribe County Hospital, Esbjerg.
Dan Med Bull. 1993 Sep;40(4):383-408.
The plasminogen activator systems in the blood, the coagulation system, and the complement pathways are reviewed. The review describes the role of the vascular intima in activation of coagulation and fibrinolysis and the interrelations between the complement system and haemostatic mechanisms. Physiological activation of fibrinolysis may be triggered by and limited to fibrin because of a special affinity of plasminogen and plasminogen activators. The binding of plasminogen to fibrin is regulated by histidine-rich glycoprotein, and the primary physiological inhibitor of generated plasmin is alpha 2-antiplasmin and especially the plasminogen-binding form of this immediate plasmin inhibitor. Plasminogen activator inhibitors in the blood, that is, notably plasminogen activator inhibitor type 1 (PAI-1), bind circulating tissue-type plasminogen activator (t-PA). However, local fibrinolysis in vivo mediated by t-PA may be independent of complex formation between plasminogen activator inhibitors and t-PA in the fluid phase. Circulating plasminogen activator inhibitors might regulate fibrinolysis by increasing the clearance of t-PA from the blood. The urokinase-type and factor XII-dependent fibrinolytic proactivator system can be activated following t-PA-mediated generation of plasmin, and could thus serve as an amplification system of t-PA-induced fibrinolysis. It is claimed that the as yet uncharacterized proactivator is essential for optimal generation of plasminogen activator activity by the factor XII-dependent fibrinolytic system. The normal antithrombotic condition of the vascular intima probably results from lack of tissue factor activity and the presence of significant antithrombotic components comprising, among others, antithrombin III and the protein C-protein S system. A number of pathophysiologic stimuli, notably mediators of the acute phase response such as the cytokines interleukin-1 and tumour necrosis factor-alpha (cachectin), have the potential to induce the vascular endothelium to express procoagulant activity. Vascular endothelium promoting coagulant activity releases increased amounts of t-PA antigen and PAI-1 antigen into the circulation, and elevated levels in the blood of both may be regarded as a marker of a generalized procoagulant condition involving the vascular endothelium. In a prospective study in patients with unstable angina pectoris, patients in whom disease progresses and acute myocardial infarction develops, have increased amounts of t-PA antigen and PAI-1 antigen in the blood. This suggests that the procoagulant potential and atherosclerotic process of the vascular intima is more pronounced in the risk group.(ABSTRACT TRUNCATED AT 400 WORDS)
本文综述了血液中的纤溶酶原激活物系统、凝血系统和补体途径。该综述描述了血管内膜在凝血和纤溶激活中的作用以及补体系统与止血机制之间的相互关系。由于纤溶酶原和纤溶酶原激活物具有特殊亲和力，纤溶的生理激活可能由纤维蛋白触发并局限于纤维蛋白。纤溶酶原与纤维蛋白的结合受富含组氨酸糖蛋白调节，所生成纤溶酶的主要生理性抑制剂是α2-抗纤溶酶，尤其是这种直接纤溶酶抑制剂的纤溶酶原结合形式。血液中的纤溶酶原激活物抑制剂，即特别是1型纤溶酶原激活物抑制剂（PAI-1），可结合循环中的组织型纤溶酶原激活物（t-PA）。然而，t-PA介导的体内局部纤溶可能独立于纤溶酶原激活物抑制剂与液相中t-PA的复合物形成。循环中的纤溶酶原激活物抑制剂可能通过增加t-PA从血液中的清除来调节纤溶。尿激酶型和因子Ⅻ依赖性纤溶前激活物系统可在t-PA介导生成纤溶酶后被激活，因此可作为t-PA诱导纤溶的放大系统。据称，尚未明确的前激活物对于因子Ⅻ依赖性纤溶系统最佳生成纤溶酶原激活物活性至关重要。血管内膜的正常抗血栓状态可能源于组织因子活性的缺乏以及包括抗凝血酶Ⅲ和蛋白C-蛋白S系统等重要抗血栓成分的存在。许多病理生理刺激，尤其是急性期反应的介质，如细胞因子白细胞介素-1和肿瘤坏死因子-α（恶病质素），有可能诱导血管内皮表达促凝活性。促进凝血活性的血管内皮会向循环中释放增加量的t-PA抗原和PAI-1抗原，血液中两者水平升高可被视为涉及血管内皮的全身性促凝状态的标志物。在一项对不稳定型心绞痛患者的前瞻性研究中，疾病进展并发生急性心肌梗死的患者血液中t-PA抗原和PAI-1抗原量增加。这表明血管内膜的促凝潜能和动脉粥样硬化过程在风险组中更为明显。（摘要截选至400词）
