Davis Medical Center, University of California, Sacramento, CA, USA.
Ann Pharmacother. 2011 Oct;45(10):1185-92. doi: 10.1345/aph.1Q177. Epub 2011 Aug 31.
While not approved by the Food and Drug Administration for treatment of heparin-induced thrombocytopenia (HIT), except in patients undergoing percutaneous interventions, the direct thrombin inhibitor bivalirudin is a treatment option that is gaining use. An initial dose of bivalirudin 0.15-0.2 mg/kg/h, adjusted to an activated partial thromboplastin time (aPTT) of 1.5-2.5 times the baseline value, has been suggested. Initial dosing in patients with renal dysfunction, including those on hemodialysis, is unclear.
To evaluate initial bivalirudin dosing requirements in patients with and without renal dysfunction, including patients on different forms of dialysis.
A retrospective analysis of 135 patients treated with bivalirudin for HIT between June 2004 and October 2009 was conducted at a tertiary care medical center. The patients were divided into groups, based on renal function. Patients receiving dialysis were divided into 3 subgroups based on the mode of hemodialysis: intermittent hemodialysis (IHD, n = 24), sustained low-efficiency daily diafiltration (SLEDD, n = 12), or continuous renal replacement therapy (CRRT, n = 5). Patients not receiving dialysis were separated into 3 subgroups based on calculated creatinine clearance (CrCl): CrCl >60 mL/min (n = 52), CrCl 30-60 mL/min (n = 26), and CrCl <30 mL/min (n = 16).
Compared with patients with normal renal function (CrCl >60 mL/min), patients with differing degrees of renal dysfunction (CrCl 30-60 and <30 mL/min) required lower doses of bivalirudin to achieve aPTT goal (0.13 vs 0.08 vs 0.05 mg/kg/h, respectively; p < 0.001). Patients on dialysis (IHD, SLEDD, CRRT) also required dose reductions (0.07, 0.09, and 0.07 mg/kg/h) compared with patients with normal renal function, but higher dosing requirements than patients not receiving dialysis with CrCl <30 mL/min.
Patients with renal dysfunction require a reduced dose of bivalirudin to reach a therapeutic aPTT goal. Slightly higher doses may be observed in patients receiving hemodialysis.
尽管直接凝血酶抑制剂比伐卢定并未获得美国食品药品监督管理局（FDA）批准用于肝素诱导的血小板减少症（HIT）的治疗，除非患者正在接受经皮介入治疗，但它是一种正在得到应用的治疗选择。目前建议的初始剂量为 0.15-0.2mg/kg/h，调整至激活的部分凝血活酶时间（aPTT）为基础值的 1.5-2.5 倍。对于包括正在接受血液透析的患者在内的肾功能不全患者，初始剂量尚不明确。
评估肾功能不全患者（包括不同形式透析患者）的初始比伐卢定给药剂量需求。
在一家三级医疗中心对 2004 年 6 月至 2009 年 10 月期间接受比伐卢定治疗 HIT 的 135 例患者进行了回顾性分析。这些患者依据肾功能分为不同的组。接受透析的患者依据透析模式分为 3 个亚组：间歇性血液透析（IHD，n=24）、持续低效每日透析滤过（SLEDD，n=12）或连续性肾脏替代治疗（CRRT，n=5）。未接受透析的患者依据计算的肌酐清除率（CrCl）分为 3 个亚组：CrCl＞60mL/min（n=52）、CrCl 30-60mL/min（n=26）和 CrCl＜30mL/min（n=16）。
与肾功能正常（CrCl＞60mL/min）的患者相比，不同程度肾功能不全（CrCl 30-60 和＜30mL/min）的患者达到 aPTT 目标所需的比伐卢定剂量较低（分别为 0.13、0.08 和 0.05mg/kg/h，p＜0.001）。与肾功能正常的患者相比，接受透析（IHD、SLEDD、CRRT）的患者也需要降低剂量（0.07、0.09 和 0.07mg/kg/h），但与接受透析的 CrCl＜30mL/min 的患者相比，需要更高的剂量。
肾功能不全患者需要降低比伐卢定剂量以达到治疗性 aPTT 目标。接受血液透析的患者可能需要略高的剂量。
