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低分子量肝素在癌症相关性血栓形成治疗中的应用:一种新的治疗标准?

Low-molecular-weight heparins in the treatment of cancer-associated thrombosis: a new standard of care?

作者信息

Burris Howard A

机构信息

Sarah Cannon Cancer Center, Nashville, TN 37203, USA.

出版信息

Semin Oncol. 2006 Apr;33(2 Suppl 4):S3-16; quiz S41-2. doi: 10.1053/j.seminoncol.2006.01.019.

Abstract

Cancer patients are twice as likely to develop postoperative venous thromboembolism (VTE) than non-cancer patients undergoing the same surgical procedure. Causes of cancer-associated thrombosis include: the capacity of tumor cells and their products to interact with platelets, clotting, and fibrinolytic proteins. Aggressive antitumor therapy with agents such as platinum compounds, high-dose fluorouracil, mitomycin-C, tamoxifen, and growth factors increase the risk of cancer-associated thrombosis. Despite the high risk of VTE in patients with cancer, thromboprophylaxis in surgical and medical oncology patients is low. Initial therapy of VTE in patients with cancer is low-molecular-weight heparin (LMWH) or unfractionated heparin. Long-term secondary prophylaxis of VTE is generally accomplished with oral anticoagulants, primarily warfarin. Evidence supports the use of LMWH for prevention and treatment of cancer-associated thrombosis because it is more easily administered, does not require laboratory monitoring, has a lower risk of adverse events, and is more cost effective than unfractionated heparin. In addition, the antineoplastic effects of LMWH have been demonstrated, including direct antitumor, antiangiogenic, and immune system modulatory action. Each LMWH is a unique biological entity having product-specific molecular and structural attributes; therefore, different LMWHs cannot be given interchangeably. Continued investigation of LMWH therapy in patients with cancer is warranted.

摘要

癌症患者术后发生静脉血栓栓塞(VTE)的可能性是非癌症患者接受相同手术的两倍。癌症相关血栓形成的原因包括:肿瘤细胞及其产物与血小板、凝血和纤维蛋白溶解蛋白相互作用的能力。使用铂类化合物、高剂量氟尿嘧啶、丝裂霉素-C、他莫昔芬和生长因子等药物进行积极的抗肿瘤治疗会增加癌症相关血栓形成的风险。尽管癌症患者发生VTE的风险很高,但手术和肿瘤内科患者的血栓预防率却很低。癌症患者VTE的初始治疗是使用低分子量肝素(LMWH)或普通肝素。VTE的长期二级预防通常通过口服抗凝剂来完成,主要是华法林。有证据支持使用LMWH预防和治疗癌症相关血栓形成,因为它更易于给药,不需要实验室监测,不良事件风险更低,并且比普通肝素更具成本效益。此外,LMWH的抗肿瘤作用也已得到证实,包括直接抗肿瘤、抗血管生成和免疫系统调节作用。每种LMWH都是具有产品特异性分子和结构特性的独特生物实体;因此,不同的LMWH不能互换使用。有必要继续对癌症患者的LMWH治疗进行研究。

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