Hoppensteadt Debra A, Jeske Walter, Walenga Jeanine, Fareed Jawed
Department of Pathology, Loyola University Chicago, Maywood, IL 60153, USA.
Semin Respir Crit Care Med. 2008 Feb;29(1):90-9. doi: 10.1055/s-2008-1047567.
The conventional management of thrombotic disorders is based on the use of heparin, oral anticoagulants, and aspirin. The development of low molecular weight heparins and the synthesis of heparinomimetics such as the chemically synthesized pentasaccharide represent a refined use of heparin. Aspirin still remains the lead drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as the adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. The oral anticoagulants such as warfarin provide a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant drugs target specific sites in the hemostatic network. There is a major thrust on the development of orally bioavailable anticoagulant drugs to replace oral anticoagulants. Heparin and low molecular weight heparins have been considered with various chemical enhancers for absorption. Both the factor Xa and antithrombin agents have been developed for oral use and some of these agents are in clinical development. Besides the limited bioavailability, the therapeutic indices of some of these drugs have been rather disappointing. Factor Xa inhibitors such as the pentasaccharides have undergone aggressive clinical development. The newer antiplatelet drugs have added a new dimension in the management of thrombotic disorders. The newer drugs are attractive for several reasons; however, none of these are expected to completely replace the conventional drugs in polytherapeutic approaches. It is conceivable that some of the newer drugs in combined modalities may mimic the broad therapeutic spectrum of heparins and warfarin. However, clinical validation is required for the therapeutic interchange for specific indications.
血栓性疾病的传统治疗方法是使用肝素、口服抗凝剂和阿司匹林。低分子量肝素的开发以及肝素类似物（如化学合成的五糖）的合成代表了肝素的精细化应用。阿司匹林仍然是血栓性和心血管疾病治疗中的主要药物。新型抗血小板药物，如二磷酸腺苷受体抑制剂、糖蛋白IIb/IIIa（GPIIb/IIIa）抑制剂和其他特异性抑制剂，效果有限，且已在接受过阿司匹林治疗的患者中进行了测试。华法林等口服抗凝剂为血栓性疾病的长期门诊治疗提供了一种方便且经济的方法。这些药物的优化使用仍然是治疗血栓性疾病的首选方法。新型抗凝药物靶向止血网络中的特定部位。目前大力推动开发口服生物可利用的抗凝药物以取代口服抗凝剂。肝素和低分子量肝素已与各种化学增强剂一起考虑用于吸收。Xa因子和抗凝血酶药物均已开发用于口服，其中一些药物正在进行临床开发。除了生物利用度有限外，其中一些药物的治疗指数也相当令人失望。五糖等Xa因子抑制剂已积极开展临床开发。新型抗血小板药物为血栓性疾病的治疗增添了新的维度。这些新药因其多种原因而具有吸引力；然而，在多药联合治疗方法中，预计它们都不会完全取代传统药物。可以想象，一些联合使用的新药可能会模仿肝素和华法林的广泛治疗谱。然而，特定适应症的治疗互换需要临床验证。
