Thompson-Moore Nathaniel R, Wanat Matthew A, Putney David R, Liebl Phuong H Nguyen, Chandler Wayne L, Muntz James E
Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA
Department of Pharmacy, Houston Methodist Hospital, Houston, TX, USA.
Clin Appl Thromb Hemost. 2015 Sep;21(6):513-20. doi: 10.1177/1076029614568713. Epub 2015 Jan 19.
The pharmacokinetic properties of enoxaparin may lead to supratherapeutic antifactor Xa (anti-Xa) levels and increased bleeding when standard treatment doses are used in patients with morbid obesity.
To evaluate the dose of enoxaparin needed to achieve therapeutic anti-Xa levels in a prospective, masked observational cohort of heterogeneous inpatients with morbid obesity and to determine whether patients with morbid obesity treated with 1 mg/kg of enoxaparin are at increased risk of supratherapeutic levels and bleeding events compared to patients receiving lower doses.
Hospitalized patients with a body mass index ≥40 kg/m(2) or actual body weight ≥140 kg and prescribed treatment doses of enoxaparin >60 mg per day were enrolled and consented to phlebotomy for determination of anti-Xa levels.
Forty-one patients were included for data analysis. The dose of enoxaparin that resulted in therapeutic and supratherapeutic anti-Xa levels at steady state was 0.83 mg/kg and 0.98 mg/kg (-0.11; 95% confidence interval [CI] -0.20 to -0.01, P = .02), respectively. Enoxaparin dose as mg/kg of actual body weight was an independent predictor of having a supratherapeutic anti-Xa level. Patients with doses <0.95 mg/kg versus ≥0.95 mg/kg were less likely to have supratherapeutic levels (odds ratio 0.21 [95% CI 0.05-0.84], P = .02) and had similar rates of subtherapeutic levels. Doses <0.95 mg/kg and ≥0.95 mg/kg resulted in similar bleeding rates of 17.9% and 22.2% (P = .71), respectively.
Patients with morbid obesity required less than the recommended 1 mg/kg enoxaparin dose to achieve therapeutic peak anti-Xa levels; therefore, initiation with lower dosages is prudent and anti-Xa monitoring should guide dosage adjustments.
在病态肥胖患者中使用标准治疗剂量时，依诺肝素的药代动力学特性可能导致抗Xa因子（抗Xa）水平高于治疗水平并增加出血风险。
在一个前瞻性、双盲观察性队列中，评估病态肥胖的异质性住院患者达到治疗性抗Xa水平所需的依诺肝素剂量，并确定与接受较低剂量的患者相比，接受1mg/kg依诺肝素治疗的病态肥胖患者出现高于治疗水平和出血事件的风险是否增加。
纳入体重指数≥40kg/m²或实际体重≥140kg且规定的依诺肝素治疗剂量>60mg/天的住院患者，并同意进行静脉穿刺以测定抗Xa水平。
41例患者纳入数据分析。达到稳态时产生治疗性和高于治疗水平的抗Xa水平的依诺肝素剂量分别为0.83mg/kg和0.98mg/kg（-0.11；95%置信区间[CI]-0.20至-0.01，P=0.02）。以实际体重mg/kg为单位的依诺肝素剂量是抗Xa水平高于治疗水平的独立预测因素。剂量<0.95mg/kg与≥0.95mg/kg的患者出现高于治疗水平的可能性较小（优势比0.21[95%CI0.05-0.84]，P=0.02），且亚治疗水平发生率相似。剂量<0.95mg/kg和≥0.95mg/kg的出血率分别为17.9%和22.2%，相似（P=0.71）。
病态肥胖患者达到治疗性抗Xa峰值水平所需的依诺肝素剂量低于推荐的1mg/kg；因此，谨慎起见应从较低剂量开始，且抗Xa监测应指导剂量调整。
