凝血酶抑制剂的研究进展

动脉和静脉血栓是发病率和死亡率均高的疾病。虽然目前可用的抗凝血剂可有效防治血栓性疾病,但各有缺点。低分子量肝素和磺达肝素能产生可预见的抗凝水平,且不需要凝血功能监测,但需注射给药,不便长期用药。华法林是一种口服有效的维生素K拮抗剂,但由于遗传多态性、膳食维生素K的摄入以及多重药物相互作用等因素,使其产生可变的抗凝反应,需要进行凝血功能监测和频繁调整剂量以确保达到抗凝治疗水平。鉴于此,以凝血因子Ⅹ和凝血酶为靶点的新型口服有效的抗血栓药成为开发热点。

Research Progress on Thrombin Inhibitor

Arterial and venous thrombosis are major causes of morbidity and mortality and, with an aging population, their incidence will increase further. Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic diseases, they have their own drawbacks. Low molecular weight heparin and fondaparinux produce a predictable level of anticoagulation without needing the coagulation monitoring, but they must be given by injection, which renders them inconvenient for long- term use. Warfarin as one of vitamin K antagonists by oral administration produces variable anticoagulant responses due to genetic polymorphisms, dietary vita- min K intake and multiple drug- drug interactions for affecting its metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. For these reasons, the new oral anticoagulants with thrombin or factor X as the target have become the development hot spot.