Drouet L, Caen J P
Hôpital Saint-Louis, Paris, France.
Semin Thromb Hemost. 1989 Apr;15(2):111-22. doi: 10.1055/s-2007-1002693.
New trends in antithrombotic therapy should reside in a better adaptation, both in potency and in target to the involved thrombogenic mechanism. Thrombogenesis as hemostasis is the result of cooperation between plasma coagulation factors and platelet functions, and these two systems are themselves in equilibrated antagonism with the vessel wall, mainly endothelial cells. These triangular relations between coagulation factors, platelet functions, and endothelial cell reactivity are quantitatively regulated by flow conditions. The relative importance of each of these protagonists in the genesis of vascular thrombosis varies along the vascular tree, mainly due to changes in flow characteristics, and explain the usual separation between venous and arterial thrombosis: venous thrombosis involves mainly coagulation factors and the vascular fibrinolytic response whereas arterial thrombosis involves the thromboresistant characteristics of the endothelial cell membrane and platelet functions. The real blood flow characteristics may be altered by local disease and influences the relative involvement of coagulation and fibrinolytic factors, platelet functions, and endothelial cells. Prevention of thrombosis must take into account all these phenomena and must be targeted to the predominant factor or factors. Depending on the local conditions, the therapeutical goal can be: (1) limitation of platelet functions or coagulation factors; (2) stimulation of thromboresistant properties of the endothelium (mainly its profibrinolytic characteristics); and (3) modification of the flow conditions. Several targets can be associated: the level of inhibition or stimulation of a function depends on the dysequilibrium, and efficient prevention does not always require complete inhibition of a function. Once a thrombus has developed, antithrombotic treatment will prevent its extension, and thrombolytic therapy will try to restore vascular patency. Once patency has been restored antithrombotic therapy is still needed to prevent recurrence of the thrombus. Even if the main targeting is on platelets, the choice in the molecule to be clinically used must be defined by the function of the platelet involved: thrombogenesis or vasospasm, and even by the metabolic pathway predominantly activated. In coagulation strategy, differences must be drawn between antithrombotic therapy directed against thrombin formation, complexes of coagulation, free enzymes or activation phases. In thrombolytic therapy all procedural uses of extrinsic thrombolytic agents (natural, modified, or artificial), increase of susceptibility to endogenous thrombolytic systems, and stimulation of endogenous thrombolytic activity do not bear the same efficiency. As a consequence, the responsibility for clinical use of new molecules with more specific activity can allow more efficient antithrombotic therapy directed at the condition of an indication targeted at the exact mechanisms involved.(ABSTRACT TRUNCATED AT 400 WORDS)
抗血栓治疗的新趋势应在于在效力和靶点方面更好地适配所涉及的血栓形成机制。血栓形成如同止血一样，是血浆凝血因子与血小板功能协同作用的结果，而这两个系统本身又与血管壁（主要是内皮细胞）处于平衡的拮抗状态。凝血因子、血小板功能与内皮细胞反应性之间的这种三角关系受到血流状况的定量调节。这些因素在血管血栓形成过程中各自的相对重要性沿血管树而异，主要是由于血流特性的变化，这也解释了静脉血栓和动脉血栓通常的区别：静脉血栓主要涉及凝血因子和血管纤维蛋白溶解反应，而动脉血栓涉及内皮细胞膜的抗血栓特性和血小板功能。局部疾病可能改变实际的血流特性，并影响凝血和纤维蛋白溶解因子、血小板功能以及内皮细胞的相对参与情况。血栓形成的预防必须考虑到所有这些现象，并且必须针对主要因素。根据局部情况，治疗目标可以是：（1）限制血小板功能或凝血因子；（2）刺激内皮的抗血栓特性（主要是其促纤维蛋白溶解特性）；（3）改变血流状况。可以联合多个靶点：对一种功能的抑制或刺激程度取决于失衡情况，有效的预防并不总是需要完全抑制一种功能。一旦血栓形成，抗血栓治疗将防止其扩展，溶栓治疗将试图恢复血管通畅。一旦恢复通畅，仍需要抗血栓治疗以防止血栓复发。即使主要靶点是血小板，临床使用分子的选择也必须根据所涉及的血小板功能来确定：血栓形成或血管痉挛，甚至要根据主要激活的代谢途径来确定。在凝血策略方面，必须区分针对凝血酶形成、凝血复合物、游离酶或激活阶段的抗血栓治疗。在溶栓治疗中，外源性溶栓剂（天然、改良或人工）的所有程序使用、对内源性溶栓系统敏感性的增加以及内源性溶栓活性的刺激，其效率并不相同。因此，具有更特异性活性的新分子的临床应用责任在于能够针对确切涉及的机制，进行更有效的抗血栓治疗。（摘要截选至400字）
