Monreal M, Costa J, Salva P
Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Drugs Aging. 1996 Mar;8(3):171-82. doi: 10.2165/00002512-199608030-00003.
Hirudin and its derivatives represent the first parenteral anticoagulants introduced since the discovery of heparin in the early 1900s. Hirudin, the naturally occurring anticoagulant of the leech, is a single peptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant forms of hirudin (r-hirudin) in sufficient quantities for therapeutic use. Hirudin is a potent thrombin-specific inhibitor that forms equimolar complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many years. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no direct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preventing or treating venous thromboembolism is very preliminary. However, r-hirudin achieved promising results in patients with unstable angina, or following coronary angioplasty. In patients with acute myocardial infarction, 3 important clinical trials were stopped because of an excess of bleeding complications. At present, the discovery of a r-hirudin regimen that is more efficacious than heparin and at least as safe needs a reappraisal of the drug in further trials.
水蛭素及其衍生物是自20世纪初发现肝素以来首次引入的肠道外抗凝剂。水蛭素是水蛭天然存在的抗凝剂，是一条由65个氨基酸组成的单肽链，分子量约为7000。重组技术已开发出方法，能够大量生产用于治疗的重组水蛭素（r-水蛭素）。水蛭素是一种强效的凝血酶特异性抑制剂，能与凝血酶形成等摩尔复合物。在肝素多年来一直是唯一可用药物的领域，它代表了一种新型抗凝剂。与肝素不同，水蛭素不需要抗凝血酶III作为辅助因子，不会被抗肝素蛋白灭活，对血小板没有直接作用，还可能使与血栓或内皮下结合的凝血酶失活。在人类中，r-水蛭素预防或治疗静脉血栓栓塞的经验非常有限。然而，r-水蛭素在不稳定型心绞痛患者或冠状动脉成形术后取得了有希望的结果。在急性心肌梗死患者中，3项重要的临床试验因出血并发症过多而停止。目前，需要在进一步试验中重新评估该药物，以发现一种比肝素更有效且至少同样安全的r-水蛭素治疗方案。
