其他抗凝药物

    

    除了普通肝素、低分子肝素以及华法林之外，还有一些其他类型及新型抗凝药物，如直接凝血酶抑制药水蛭素及其衍生物比伐卢定等。

    对不稳定型心绞痛、非ST段抬高型心肌梗死和ST段抬高心肌梗死的治疗，水蛭素至少与肝素等效。然而，由于治疗窗窄和相关的出血危险，水蛭素未被批准用于治疗急性冠状动脉综合征的常规治疗药物。尽管水蛭素对静脉血栓形成的预防和治疗似乎具有前景，但需要进行更多的临床试验以提供更充分的证据。

    比伐卢定是水蛭素的类似物，是一种含有20个氨基酸的合成多肽。由于抗凝反应可以预测，半衰期短，比伐卢定可以应用于经皮冠状动脉介入治疗的患者。在这种情形下，比伐卢定似乎与肝素等效而引起的出血较少。对于未接受辅助性糖蛋白Ⅱb／Ⅲa受体拮抗药的具有较高出血危险的经皮冠状动脉介入患者，比伐卢定可能是比肝素更好的选择。比伐卢定可以作为肝素的替代，用于急性ST段抬高型心肌梗死患者链激酶溶栓的辅助治疗。比伐卢定与肝素相比，可以降低再梗死的危险。但是，比伐卢定治疗需要监测，并且需要剂量调整以减小出血危险。目前对比伐卢定不同研究方案的比较之间存在偏倚；而且短期和长期随访结果表明，出血风险的降低对于转归无影响。

    磺达肝癸钠是一种生物合成的Ⅹa抑制药，OASIS-5及OASIS-6试验均证明，磺达肝癸钠治疗的获益明确优于依诺肝素，而且其出血和缺血的相对风险显著降低。但是，导管血栓问题是磺达肝癸钠面临的一个问题。虽然使用Ⅹa抑制药后，PCI的一些合并症如假性动脉瘤和大血肿的发生率降低，但是使用磺达肝癸钠后，导管血栓的发生率却增加，为避免血栓可以在PCI术中按标准剂量应用肝素，以降低导管内血栓问题，而不增加出血风险。其疗效有待进一步临床验证。

    参考文献

    ［1］ Antman EM，Hand M，Armstrong PW，et al．2007Focused Update of the ACC／AHA 2004Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction：a report of the American College of Cardiology／American Heart Association Task Force on Practice Guidelines：developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians：2007Writing Group to Review New Evidence and Update the ACC／AHA 2004Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction，Writing on Behalf of the 2004Writing Committee［J］．Circulation，2008，117：296-329．

    ［2］ Anderson JL，Adams CD，Antman EM，et al．ACC／AHA 2007guidelines for the management of patients with unstable angina／non ST-elevation myocardial infarction：a report of the American College of Cardiology／American Heart Association Task Force on Practice Guidelines（Writing Committee to Revise the 2002Guidelines for the Management of Patients With Unstable Angina／Non ST-Elevation Myocardial Infarction）：developed in collaboration with the American College of Emergency Physicians，the Society for Cardiovascular Angiography and Interventions，and the Society of Thoracic Surgeons：endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine［J］．Circulation，2007，116：e148-304．

    ［3］ Cruz-Gonzalez I，Sanchez-Ledesma M，Sanchez PL，et al．Heparin-induced thrombocytopenia［J］．Rev Esp Cardiol，2007，60：1071-1082．

    ［4］ Rauova L，Poncz M，McKenzie SE，et al．Ultralarge complexes of PF4and heparin are central to the pathogenesis of heparin-induced thrombocytopenia［J］．Blood，2005，105：131-138．

    ［5］ Yuan F，Lu SZ，Chen YD，et al．The application of a 0．75mg／kg intra-arterial dose of enoxaparin in coronary angiography and percutaneous coronary intervention［J］．Zhonghua Nei Ke Za Zhi，2007，46：200-2033．

    ［6］ Khoobiar S，Mejevoi N，Kaid K，et al．Primary percutaneous coronary intervention for ST-elevation myocardial infarction using an intravenous and subcutaneous enoxaparin low molecular weight heparin regimen［J］．J Thromb Thrombolysis，2008，26：85-90．

    ［7］ King SB 3rd，Smith SC Jr，Hirshfeld JW Jr，et al．2007Focused Update of the ACC／AHA／SCAI 2005Guideline Update for Percutaneous Coronary Intervention：a report of the American College of Cardiology／American Heart Association Task Force on Practice Guidelines：2007Writing Group to Review New Evidence and Update the ACC／AHA／SCAI 2005Guideline Update for Percutaneous Coronary Intervention，Writing on Behalf of the 2005Writing Committee［J］．Circulation，2008，117：261-295．

    ［8］ Ugaki H，Enomoto T，Fujiwara K，et al．Safety and efficacy of lower-dose unfractionated heparin for prophylaxis of deep vein thrombosis and pulmonary embolism in an Asian population［J］．Blood Coagul Fibrinolysis，2008，19：585-589．

    ［9］ Hull RD．Treatment of pulmonary embolism：The use of low-molecular-weight heparin in the inpatient and outpatient settings［J］．Thromb Haemost，2008，99：502-510．

    ［10］ British Thoracic Society guidelines for the management of suspected acute pulmonary embolism［J］．Thorax，2003，58：470-483．

    ［11］ Hirsh J，Fuster V，Ansell J，et al．American Heart Association／American College of Cardiology Foundation guide to warfarin therapy［J］．Circulation，2003，107：1692-1711．

    ［12］ Poli D，Antonucci E，Marcucci R，et al．Risk of bleeding in very old atrial fibrillation patients on warfarin：relationship with ageing and CHADS2score［J］．Thromb Res，2007，121：347-352．

    ［13］ Fuster V，Ryden LE，Cannom DS，et al．ACC／AHA／ESC 2006guidelines for the management of patients with atrial fibrillation：full text：a report of the American College of Cardiology／American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines（Writing Committee to Revise the 2001guidelines for the management of patients with atrial fibrillation）developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society［J］．Europace，2006，8：651-745．

    ［14］ 马俊义，袁雅冬．肺血栓栓塞症的现代药物治疗新指南．实用心脑肺血管病杂志［J］，2006，14：96-98．

    ［15］ Bates SM，Weitz JI．New anticoagulants：beyond heparin，low-molecular-weight heparin and warfarin［J］．Br J Pharmacol，2005，144：1017-1028．

    ［16］ Kastrati A，Neumann FJ，Mehilli J，et al．Bivalirudin versus unfractionated heparin during percutaneous coronary intervention［J］．N Engl J Med，2008，359：688-696．

    ［17］ Ramana RK，Lewis BE．Percutaneous coronary intervention in patients with acute coronary syndrome：focus on bivalirudin［J］．Vasc Health Risk Manag，2008，4：493-505．

    ［18］ Yusuf S，Mehta SR，Chrolavicius S，et al．Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction：the OASIS-6 randomized trial［J］．JAMA，2006，295：1519-1530．