Centre Spécialisé de l'obésité (CSO) PACA Ouest, France; Endocrinology, Metabolic Diseases and Nutrition Department, Pole ENDO, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France; Aix Marseille Univ, INSERM, UMR1263, INRA, C2VN, Marseille, France.
Hematology Department, Timone Hospital, Assistance Publique - Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France.
Pharmacol Res. 2018 May;131:211-217. doi: 10.1016/j.phrs.2018.02.012. Epub 2018 Feb 13.
Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m (IQR, 40.6-48.7 kg/m)] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r = -0.56, p < .0001). Receiver operating characteristic curves indicated that among BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (β = -0.47 ± 0.08, p < .0001 and β = -0.19 ± 0.08; p = .02, respectively). In BS morbidly obese patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the main determinants of anti-Xa level, and could be proposed in LMWH-based thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing algorithm for optimal VTE prevention deserves further prospective randomized trials.
接受减重手术（BS）的重度肥胖患者发生静脉血栓栓塞症（VTE）的风险增加。在这种情况下，应如何调整标准的低分子量肝素（LMWH）方案以既提供足够的疗效又确保安全性尚不清楚。我们旨在比较四种体型描述符（BSD）对接受 LMWH 固定剂量的 BS 肥胖患者抗 Xa 峰值水平的影响，以确定哪种影响最大。本前瞻性单中心研究纳入了 113 例接受皮下达肝素 5000IU 每日两次的 BS 肥胖患者[中位数体重指数（BMI），43.3kg/m（IQR，40.6-48.7kg/m）]。在开始抗血栓预防后，围手术期测量了抗 Xa 峰值稳态水平。只有 48%的患者达到了目标抗 Xa 水平（0.2-0.5IU/ml）。在单变量分析中，年龄、性别、总体体重（TBW）、瘦体重（LBW）、理想体重（IBW）、BMI 和估计肾小球滤过率（eGFR）与抗 Xa 水平相关。与 LBW 呈最强的负相关（r=-0.56，p<0.0001）。受试者工作特征曲线表明，在 BSD 中，LBW（>55.8kg 的截断值）对预测亚预防抗 Xa 水平的敏感性（73%）和特异性（69%）最高。在多变量分析中，LBW 和 eGFR 仍然与抗 Xa 水平相关（β=-0.47±0.08，p<0.0001 和β=-0.19±0.08；p=0.02）。在接受 LMWH 进行 BS 后血栓预防的 BS 病态肥胖患者中，LBW 和 eGFR 是抗 Xa 水平的主要决定因素，可用于 LMWH 为基础的血栓预防剂量算法中。基于 LBW 量表的剂量算法对最佳 VTE 预防的疗效值得进一步前瞻性随机试验。
