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低分子量肝素在肥胖者、老年人及肾功能不全患者中的应用。

Low-molecular-weight heparin use in the obese, elderly, and in renal insufficiency.

作者信息

Clark N P

机构信息

Clinical Pharmacy Anticoagulation Service, Kaiser Permanente Colorado, Clinical Assistant Professor, University of Colorado Denver School of Pharmacy, Denver, CO, USA.

出版信息

Thromb Res. 2008;123 Suppl 1:S58-61. doi: 10.1016/j.thromres.2008.08.005. Epub 2008 Sep 21.

Abstract

Superior bioavailability and simple weight-based dosing have made low-molecular-weight heparins (LMWH) the preferred agents for treatment and prevention of venous thromboembolism (VTE) for most indications. Despite improved pharmacokinetics, there remain populations where appropriate LMWH dose intensity and frequency are open to question. Obese patients have a lower proportion of lean body mass as a percentage of total body weight. As a result, LMWH dosing based on total body weight could cause supra-therapeutic anticoagulation. Elderly patients also have less lean body mass in addition to a higher incidence of age-related renal disease and increased risk of bleeding. Renal insufficiency presents a risk of LMWH accumulation as well as increased risk of bleeding. Among LMWH products, only dalteparin labeling recommends a maximum dose. Prospective data call into question the validity of this dose limitation. Additionally, because obese patients are already at higher risk of VTE recurrence, they may be particularly sensitive to subtherapeutic anticoagulation. Prospective data evaluating LMWH use in elderly patients have been limited to in-patient treatment. Few recommendations can be made in this population other than close monitoring. Renal insufficiency is a risk for bleeding during LMWH use. Available evidence supports the potential for enoxaparin accumulation, but not tinzaparin. Enoxaparin dose adjustment, either empiric or based on anti-Xa monitoring, has insufficient data to support widespread implementation. Unfractionated heparin is not reliant on renal elimination and is a sensible option for VTE treatment in patients with a creatinine clearance<30 ml/min.

摘要

较高的生物利用度和基于体重的简单给药方式,使低分子肝素(LMWH)成为大多数适应症下治疗和预防静脉血栓栓塞(VTE)的首选药物。尽管药代动力学有所改善,但仍有部分人群,适当的LMWH剂量强度和给药频率仍存在疑问。肥胖患者的瘦体重占总体重的比例较低。因此,基于总体重的LMWH给药可能导致抗凝作用超治疗剂量。老年患者除了与年龄相关的肾病发病率较高和出血风险增加外,瘦体重也较少。肾功能不全存在LMWH蓄积的风险以及出血风险增加。在LMWH产品中,只有达肝素的标签推荐了最大剂量。前瞻性数据对这种剂量限制的有效性提出了质疑。此外,由于肥胖患者已经有较高的VTE复发风险,他们可能对抗凝不足特别敏感。评估老年患者使用LMWH的前瞻性数据仅限于住院治疗。除了密切监测外,针对该人群几乎无法给出其他建议。肾功能不全是LMWH使用期间出血的一个风险因素。现有证据支持依诺肝素可能会蓄积,但不支持替扎肝素。依诺肝素的剂量调整,无论是经验性调整还是基于抗Xa监测进行调整,都缺乏足够的数据支持广泛应用。普通肝素不依赖肾脏清除,对于肌酐清除率<30 ml/min的VTE患者,是一种合理的治疗选择。

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