Schmid Pirmin, Fischer Andreas G, Wuillemin Walter A
Division of Haematology and Central Haematology Laboratory, Department of Medicine, Kantonsspital Luzern, Luzern, Switzerland.
Swiss Med Wkly. 2009 Aug 8;139(31-32):438-52. doi: 10.4414/smw.2009.11284.
Low-molecular-weight heparins (LMWH) have been shown to be safer, more effective and more convenient than unfractionated heparin (UFH) in many clinical situations. However, their use is limited in patients with renal insufficiency (RI) due to bioaccumulation.
The literature is critically reviewed and known pharmacokinetic properties are summarised. An approach to using LMWH in patients with RI is proposed on the basis of currently available evidence.
Pharmacokinetic data of commonly used LMWH and of UFH are summarised in respect of RI. Most data are known on enoxaparin. A dose reduction is recommended in patients with severe RI. Limited data on dalteparin and tinzaparin suggest that there is less bioaccumulation. However, further studies are needed, in respect of long-term use and clinical end-points in particular.There are no data on certoparin and only very limited data on nadroparin. A detailed approach is suggested for the use of LMWH in patients with severe RI. Briefly: (1) before using LMWH, evaluate the patient's renal function, ist expected course, imminent interventions, and general bleeding risk; (2) prefer LMWH to UFH in view of better efficacy and lower bleeding risk in general; (3) however, prefer i.v. UFH to s.c. LMWH if a patient is unstable, is awaiting emergency interventions, or has a high bleeding risk, since UFH can be stopped more quickly due to i.v. administration, has a shorter half-life time, and can be effectively antagonised; (4) prefer a well documented LMWH; use established dosing schemes; (5) monitor LMWH with peak anti-Xa levels in patients with severe RI regularly, and adjust dose to be in target range; (6) do not use LMWH in patients with severe RI if there is no possibility of measuring anti-Xa levels.
LMWH may be considered for patients with severe RI. However, experience, judicious choice and careful monitoring of patients with severe RI treated with LMWH are necessary.
在许多临床情况下，低分子量肝素（LMWH）已被证明比普通肝素（UFH）更安全、更有效且更方便。然而，由于生物蓄积作用，其在肾功能不全（RI）患者中的应用受到限制。
对文献进行严格审查并总结已知的药代动力学特性。基于现有证据，提出在RI患者中使用LMWH的方法。
总结了常用LMWH和UFH在RI方面的药代动力学数据。关于依诺肝素的数据最多。建议重度RI患者减少剂量。关于达肝素和替扎肝素的数据有限，提示生物蓄积较少。然而，特别是在长期使用和临床终点方面，还需要进一步研究。关于克赛没有数据，关于那屈肝素仅有非常有限的数据。针对重度RI患者使用LMWH提出了详细方法。简要如下：（1）在使用LMWH之前，评估患者的肾功能、预期病程、即将进行的干预措施以及总体出血风险；（2）鉴于总体上疗效更好且出血风险更低，优先选择LMWH而非UFH；（3）然而，如果患者不稳定、正在等待紧急干预或出血风险高，则优先选择静脉注射UFH而非皮下注射LMWH，因为静脉注射UFH可因静脉给药而更快停药，半衰期更短，且可有效拮抗；（4）优先选择记录完善的LMWH；采用既定的给药方案；（5）定期监测重度RI患者LMWH的抗Xa峰值水平，并调整剂量使其处于目标范围；（6）如果无法测量抗Xa水平，则重度RI患者不使用LMWH。
重度RI患者可考虑使用LMWH。然而，对于接受LMWH治疗的重度RI患者，经验、明智的选择和仔细的监测是必要的。
