Maffrand J P
Sanofi Recherche, Toulouse, France.
Nouv Rev Fr Hematol (1978). 1992;34(6):405-19.
Thrombin not only plays an important role in thrombosis and haemostasis but may also be involved in other pathological situations such as the progression of atherosclerotic plaque formation, inflammatory response and neurodegenerescence. It is therefore important to be able to control the action and/or the generation of this enzyme. With this aim in view, a great number of synthetic or recombinant direct thrombin inhibitors have recently been made. They block either the thrombin catalytic site or an anion-binding exosite which is a recognition site for some of its substrates (fibrinogen, thrombin receptor, thrombomodulin, heparin cofactor II) or act on both sites. Some of these inhibitors have revealed a number of advantages over heparin in experimental animal models of thrombosis and haemorrhagic risk. On-going clinical studies with some candidates will establish their real interest for patients.
凝血酶不仅在血栓形成和止血过程中发挥重要作用，还可能参与其他病理情况，如动脉粥样硬化斑块形成、炎症反应和神经退变的进展。因此，能够控制这种酶的作用和/或生成非常重要。出于这一目的，最近已制备了大量合成或重组的直接凝血酶抑制剂。它们要么阻断凝血酶催化位点，要么阻断阴离子结合外位点，该位点是其一些底物（纤维蛋白原、凝血酶受体、血栓调节蛋白、肝素辅因子II）的识别位点，或者作用于这两个位点。在血栓形成和出血风险的实验动物模型中，其中一些抑制剂已显示出相对于肝素的若干优势。对一些候选药物正在进行的临床研究将确定它们对患者的实际价值。
