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肝素在抗血栓治疗中的当代应用及未来作用

Contemporary use of and future roles for heparin in antithrombotic therapy.

作者信息

Gibaldi M, Wittkowsky A K

机构信息

School of Pharmacy, University of Washington, Seattle 98195, USA.

出版信息

J Clin Pharmacol. 1995 Nov;35(11):1031-45. doi: 10.1002/j.1552-4604.1995.tb04023.x.

Abstract

Although heparin therapy is an established component of the prevention and treatment of thromboembolic disease, recent advances have resulted in improvements in the clinical use of this agent. Studies have shown that weight-based dosing influences significantly both the time to reach a therapeutic intensity of anticoagulation and the incidence of thromboembolic recurrence. It is now considered the standard of care. A growing understanding of the variability among activated partial thromboplastin time (aPTT) reagents and the influence of these differences on aPTT outcomes has led to the use of reagent-specific therapeutic ranges for heparin monitoring. Many practitioners now choose to adjust the therapeutic range to correspond to heparin serum concentrations of 0.2-0.4 U/mL rather than the more common practice of prolonging aPTT to 1.5-2.5 times the mean normal aPTT. Pharmaceutical companies have developed low molecular weight heparins to minimize adverse effects associated with unfractionated heparin. More specific thrombin inhibitors are also under investigation with the aim of improving clinical outcomes in coronary syndromes now treated with heparin. Low molecular weight heparins or specific thrombin inhibitors are unlikely to replace unfractionated heparin in the near future. Therefore, optimum dosing and appropriate monitoring of heparin are critically important in the management of thromboembolic disease.

摘要

尽管肝素疗法是预防和治疗血栓栓塞性疾病的既定组成部分,但最近的进展已使该药物的临床应用得到改善。研究表明,基于体重的给药显著影响达到抗凝治疗强度的时间和血栓栓塞复发的发生率。现在它被视为护理标准。对活化部分凝血活酶时间(aPTT)试剂之间的变异性以及这些差异对aPTT结果的影响的日益了解,已导致使用针对试剂的治疗范围来监测肝素。现在许多从业者选择将治疗范围调整为对应于肝素血清浓度0.2 - 0.4 U/mL,而不是更常见的将aPTT延长至正常平均aPTT的1.5 - 2.5倍的做法。制药公司已开发出低分子量肝素,以尽量减少与普通肝素相关的不良反应。更具特异性的凝血酶抑制剂也在研究中,目的是改善目前用肝素治疗的冠状动脉综合征的临床结果。低分子量肝素或特异性凝血酶抑制剂在不久的将来不太可能取代普通肝素。因此,在血栓栓塞性疾病的管理中,肝素的最佳给药和适当监测至关重要。

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