Agnelli G
Istituto di Medicina Interna e Medicina Vascolare, Universitá di Perugia, Italy.
Chest. 1995 Jan;107(1 Suppl):39S-44S. doi: 10.1378/chest.107.1_supplement.39s.
The anticoagulant agents commonly used in prevention and treatment of pulmonary embolism are unfractionated heparin, and more recently, low molecular weight heparins, and oral anticoagulants. Unfractionated heparin is the drug of choice for prophylaxis and short-term treatment of pulmonary embolism. Oral anticoagulants are used for prophylaxis in high risk patients and in long-term treatment of pulmonary embolism. Independent overview analysis of clinical trials in elective surgery showed a 60 to 70% reduction in the incidence of fatal pulmonary embolism in heparin-treated patients when they were compared with placebo-treated patients. Low dose heparin has also been shown to be effective in reducing venous thromboembolism after myocardial infarction and other serious medical disorders. In high risk patients prophylaxis with low molecular weight heparins or adjusted doses of unfractionated heparin is recommended. The objectives of treating patients with pulmonary embolism are to prevent death, to reduce morbidity from the acute event, and to prevent thromboembolic pulmonary hypertension. These objectives are achieved by the administration of heparin followed by oral anticoagulants. Heparin is generally administered for 7 to 10 days and is followed by oral anticoagulants. Although widely used and effective in the prevention and treatment of pulmonary embolism, unfractionated heparin has some pharmacological limitations. Heparin presents an aspecific "nonfunctional" binding to plasma proteins such as fibrinogen, factor VIII, vitronectin, and fibronectin. This aspecific binding limits the anticoagulant effect of unfractionated heparin and, is responsible for the heparin resistance observed in some patients with pulmonary embolism as well as of the high intersubject variability of the heparin-induced anticoagulant effect. Antithrombotic agents, such as low molecular weight heparins and pure thrombin inhibitors (hirudin and its analogues), do not specifically bind to plasma protein and they will probably improve the efficacy and practicality of the treatment of pulmonary embolism.
预防和治疗肺栓塞常用的抗凝剂有普通肝素，以及近年来使用的低分子肝素和口服抗凝剂。普通肝素是预防和短期治疗肺栓塞的首选药物。口服抗凝剂用于高危患者的预防和肺栓塞的长期治疗。对择期手术临床试验的独立综述分析表明，与接受安慰剂治疗的患者相比，接受肝素治疗的患者致命性肺栓塞的发生率降低了60%至70%。低剂量肝素也已被证明可有效降低心肌梗死和其他严重内科疾病后的静脉血栓栓塞。对于高危患者，建议使用低分子肝素或调整剂量的普通肝素进行预防。治疗肺栓塞患者的目标是预防死亡、降低急性事件的发病率以及预防血栓栓塞性肺动脉高压。这些目标通过先使用肝素然后使用口服抗凝剂来实现。肝素一般使用7至10天，之后使用口服抗凝剂。尽管普通肝素在肺栓塞的预防和治疗中广泛使用且有效，但它有一些药理学局限性。肝素与血浆蛋白如纤维蛋白原、因子VIII、玻连蛋白和纤连蛋白存在非特异性的“无功能”结合。这种非特异性结合限制了普通肝素的抗凝作用，也是一些肺栓塞患者出现肝素抵抗以及肝素诱导的抗凝作用个体间差异较大的原因。抗血栓药物，如低分子肝素和纯凝血酶抑制剂（水蛭素及其类似物），不会特异性结合血浆蛋白，它们可能会提高肺栓塞治疗的疗效和实用性。
