Sofjan Amelia K, Iuppa Jennifer A, Bain K Bennett, Deal Eli N, Witt Chad A, Hachem Ramsey R, Yusen Roger D
Barnes-Jewish Hospital, St Louis, MO, USA University of Houston College of Pharmacy, Houston, TX, USA
Barnes-Jewish Hospital, St Louis, MO, USA University of Rochester Medical Center, Rochester, NY, USA.
Ann Pharmacother. 2016 Oct;50(10):824-31. doi: 10.1177/1060028016656434. Epub 2016 Jun 29.
Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear.
To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels.
We conducted a single-center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA-approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding.
Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard-dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels.
Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients.
肺移植受者常出现需要抗凝治疗的并发症。美国食品药品监督管理局（FDA）批准的依诺肝素在该人群中的标准剂量导致抗Xa水平高于目标值的发生率较高，但其与出血的关联仍不明确。
评估依诺肝素剂量与肺移植受者出血之间的关联，并评估剂量与抗Xa水平之间的关系。
我们对2000年至2012年在一家三级学术中心接受治疗性依诺肝素的成年肺移植受者进行了一项单中心回顾性队列研究。我们将依诺肝素给药方案分为标准剂量（FDA批准的剂量，有10%的舍入余量）和减量。临床医生根据临床情况酌情安排抗Xa水平检测。主要结局是大出血或具有临床意义的非大出血。
在222例接受依诺肝素治疗的患者中，33例（14.9%）发生出血事件，其中一半（17/33）为大出血。接受标准剂量依诺肝素的146例患者中有25例（17.1%）出血，而接受减量依诺肝素的76例患者中有8例（10.5%）出血（P = 0.190）。多因素logistic回归显示，在调整混杂因素后，标准剂量依诺肝素与出血之间存在独立关联（调整后的比值比 = 3.04；95%置信区间 = 1.14 - 8.10）。抗Xa水平高于目标值与达到目标值的患者中，依诺肝素的中位剂量分别为每12小时0.89 mg/kg和0.76 mg/kg；P = 0.006。然而，产生目标抗Xa水平的剂量的四分位间距为0.67至0.90 mg/kg，与产生高于和低于目标抗Xa水平的剂量范围重叠。
依诺肝素减量及抗Xa水平监测可提高肺移植受者的用药安全性，并有助于实现个体化剂量优化。
