Department of Medicine, Division of Hematology-Thromboembolism, McMaster University, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada.
J Thromb Thrombolysis. 2010 Feb;29(2):233-40. doi: 10.1007/s11239-009-0418-z.
Clinical trials evaluating low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism and acute coronary syndromes have led to their regulatory approval for these indications in the general population. However, certain patient populations have been excluded from these landmark clinical trials, including patients with renal insufficiency, obese patients and pregnant women. In these special populations, data on safety and efficacy is limited and typically based on pharmacokinetic studies often performed in healthy subjects, or small cohort studies which are generally not powered to evaluate clinical outcomes such as bleeding or recurrent thrombosis. Because LMWH is mainly cleared renally, patients with severe renal insufficiency are at risk of LMWH accumulation and increased bleeding risks. In obese patients, there is concern regarding possible overdosing of therapeutic dose LMWH, since LMWH does not distribute in fat tissue. There are also concerns about possible underdosing of prophylactic dose LMWH in obese individuals using the standard fixed doses, particularly in the extremely obese individuals undergoing bariatric surgery. Last, pregnancy poses challenges with regards to the safety of LMWH during pregnancy and use of LMWH around delivery. This review summarizes the existing data in these special populations and proposes general recommendations for practice.
评估低分子量肝素（LMWH）在预防和治疗静脉血栓栓塞症和急性冠状动脉综合征中的临床试验，导致其在普通人群中获得了这些适应症的监管批准。然而，某些患者群体被排除在这些具有里程碑意义的临床试验之外，包括肾功能不全、肥胖和孕妇患者。在这些特殊人群中，安全性和疗效的数据有限，通常基于在健康受试者中进行的药代动力学研究，或通常没有能力评估出血或复发性血栓等临床结局的小型队列研究。由于 LMWH 主要通过肾脏清除，因此严重肾功能不全的患者存在 LMWH 蓄积和出血风险增加的风险。在肥胖患者中，人们担心治疗剂量的 LMWH 可能会过量，因为 LMWH 不会分布在脂肪组织中。此外，人们还担心在使用标准固定剂量的肥胖患者中，预防性剂量的 LMWH 可能会剂量不足，尤其是在接受减肥手术的极度肥胖患者中。最后，妊娠给 LMWH 在妊娠期间的安全性以及在分娩前后使用 LMWH 带来了挑战。本综述总结了这些特殊人群中的现有数据，并提出了一般实践建议。
