Gram J
Department of Chemical Chemistry, Ribe County Hospital, Esbjerg.
Dan Med Bull. 1990 Jun;37(3):210-34.
The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibition in plasma was optimized and simplified. The amidolytic assay of antithrombin-III was shown to be influenced by adsorption to laboratory utensils and aggregation of thrombin. This error could be corrected by protection with additives (Tween 80, polyethyleneglycol 6,000), which also improved the solubility of the chromogenic substrates in aqueous media. The role of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)
回顾了止血平衡的概念，并探讨了其在组织修复调节和血栓形成过程发病机制中的潜在作用。凝血的生理激活似乎主要受血管壁退变和受损细胞的影响，导致局部释放凝血活酶并暴露激活表面。凝血抑制会损害其进展，正常内皮的非血栓形成特性主要是由抑制成分（抗凝血酶III、蛋白C）与特定受体位点结合所致。纤维蛋白溶解的生理激活似乎是由纤维蛋白引发并局限于纤维蛋白，因为纤溶酶原和纤溶酶原激活剂对纤维蛋白具有特异性亲和力。纤维蛋白溶解的全身激活受到初级（α2 - 抗纤溶酶）和次级（α2 - 巨球蛋白、α1 - 抗胰蛋白酶）纤溶酶抑制剂的抑制。一种纤溶酶原结合蛋白（富含组氨酸的糖蛋白）、纤溶酶抑制剂和激活剂抑制剂似乎有助于调节纤维蛋白溶解的初始阶段。调节纤维蛋白形成和溶解的动态平衡偏离正常可能导致出血和/或血栓形成倾向状态。描述了评估止血平衡相关变量的选定方法的优化。当使用基于链激酶激活纤溶酶原随后水解合成显色底物的检测方法时，纤维蛋白原或纤维蛋白降解产物水平升高的患者血浆中纤溶酶原浓度可能被高估。在纤溶酶原检测中加入过量纤维蛋白原可消除此误差来源，从而确保纤溶酶原 - 链激酶复合物受到最大刺激。血浆中冷球蛋白的存在会干扰纤溶酶原激活剂活性的优球蛋白评估。实验表明组织型纤溶酶原激活剂可吸附冷球蛋白，并且纤维蛋白溶解的因子XII依赖性前激活剂系统的冷促进激活与冷球蛋白的存在有关。实验支持存在一种尚未表征的因子XII依赖性前激活剂。推荐了严格优化的优球蛋白制备程序以准确测定纤溶酶原激活剂。血浆中纤溶酶原激活剂抑制的测定得到了优化和简化。抗凝血酶III的酰胺水解检测显示受实验室器具吸附和凝血酶聚集的影响。此误差可通过添加保护剂（吐温80、聚乙二醇6000）来纠正，这也提高了显色底物在水性介质中的溶解度。综述了血栓形成在心肌梗死中的作用。（摘要截断于400字）
