College of Pharmacy and Health Sciences, Mercer University, Atlanta Campus, Atlanta, GA, USA.
Ann Pharmacother. 2010 Dec;44(12):2023-7. doi: 10.1345/aph.1P403. Epub 2010 Nov 23.
To report 3 cases of venous thromboembolism (VTE) in patients with end-stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH) bridged with warfarin.
Three patients with ESRD were successfully treated for VTE with unmonitored, fixed-dose subcutaneous UFH every 12 hours and dose-adjusted warfarin. The first patient was initiated on continuous infusion UFH for deep-vein thrombosis, but due to poor vascular access, nurses were unable to consistently measure anti-Xa levels. Therefore, subcutaneous UFH 17,500 units (∼245 units/kg/dose) every 12 hours was initiated. Oral warfarin 5 mg/day was started the following day. The patient received 4 days of inpatient subcutaneous UFH and then was discharged to complete the bridge as an outpatient. The second patient received subcutaneous UFH 10,000 units (∼244 units/kg/dose) every 12 hours and oral warfarin 2.5 mg/day to treat a nonocclusive thrombus along her right femoral vein hemodialysis catheter. The patient received 1 day of inpatient subcutaneous UFH treatment prior to discharge and continued bridge therapy with warfarin as an outpatient. The third patient was initiated on subcutaneous UFH 20,000 units (∼223 units/kg/dose) every 12 hours and oral warfarin 7.5 mg/day due to a subtherapeutic INR (1.50) 5 days after receiving fresh frozen plasma to reduce her therapeutic INR for a procedure. The patient received 2 doses of subcutaneous UFH as an inpatient before treatment was discontinued because her INR was therapeutic at 2.3.
Subcutaneous UFH has been used to treat VTE since the early 1980s; however, with the advent of low-molecular-weight heparin (LMWH), subcutaneous UFH use diminished. Several studies comparing the use of subcutaneous UFH to both continuous infusion UFH and LMWH concluded that subcutaneous UFH is a safe and efficacious alternative. The 2008 Chest Guidelines for Antithrombotic Therapy for Venous Thromboembolic Disease support the use of subcutaneous UFH for the treatment of VTE with a Grade 1A recommendation and provide a Grade 2C recommendation for use of UFH over LMWH for patients with VTE and severe renal failure.
Safe and convenient treatment options for VTE in patients with ESRD are limited. Fixed-dose, unmonitored subcutaneous UFH as a bridge to warfarin therapy is an effective option in patients with ESRD and those with financial restrictions. The pharmacist plays a key role in identifying patients for whom subcutaneous UFH treatment may be a viable alternative, recommending an appropriate dosing regimen, and educating health-care professionals and patients about safe use.
报告 3 例接受皮下非肝素（UFH）桥接华法林治疗的终末期肾病（ESRD）患者发生静脉血栓栓塞症（VTE）。
3 例 ESRD 患者成功接受了未经监测、固定剂量每 12 小时皮下 UFH 和剂量调整华法林治疗。第 1 例患者因深静脉血栓形成开始接受连续静脉滴注 UFH，但由于血管通路不佳，护士无法持续测量抗 Xa 水平。因此，开始每 12 小时皮下给予 17500 单位 UFH（约 245 单位/公斤/剂量）。第 2 天开始口服华法林 5 毫克/天。患者接受了 4 天的住院皮下 UFH 治疗，然后出院作为门诊患者完成桥接治疗。第 2 例患者因右股静脉血液透析导管内非闭塞性血栓接受每 12 小时皮下给予 10000 单位 UFH（约 244 单位/公斤/剂量）和 2.5 毫克/天的口服华法林治疗。在出院前，患者接受了 1 天的住院皮下 UFH 治疗，并继续接受华法林门诊桥接治疗。第 3 例患者因治疗 INR（1.50）在接受新鲜冷冻血浆以降低治疗 INR 后第 5 天降至亚治疗范围，开始接受每 12 小时皮下给予 20000 单位 UFH（约 223 单位/公斤/剂量）和 7.5 毫克/天的口服华法林治疗。由于 INR 达到治疗范围（2.3），患者在接受 2 次皮下 UFH 治疗后停止治疗。
自 20 世纪 80 年代初以来，皮下 UFH 一直用于治疗 VTE；然而，随着低分子量肝素（LMWH）的出现，皮下 UFH 的使用减少了。一些比较皮下 UFH 与连续静脉滴注 UFH 和 LMWH 应用的研究得出结论，皮下 UFH 是一种安全有效的替代方案。2008 年《胸部血栓栓塞症抗血栓治疗指南》支持使用皮下 UFH 治疗 VTE，其推荐级别为 1A，并推荐对 VTE 和严重肾功能衰竭患者使用 UFH 而非 LMWH，推荐级别为 2C。
ESRD 患者 VTE 的安全有效治疗选择有限。在 ESRD 患者和有经济限制的患者中，固定剂量、未经监测的皮下 UFH 桥接华法林治疗是一种有效的选择。药剂师在确定哪些患者可能适合皮下 UFH 治疗方面发挥着关键作用，药剂师可以推荐适当的剂量方案，并向医疗保健专业人员和患者提供安全使用方面的教育。
