Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands; Pharmacy Foundation of Haarlem Hospitals, Haarlem, the Netherlands; Department of Clinical Pharmacy, Spaarne Gasthuis Hospital, Haarlem/Hoofddorp, the Netherlands.
Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands; Department of Hospital Pharmacy, Elisabeth TweeSteden Hospital, Tilburg, the Netherlands.
Thromb Res. 2024 Apr;236:4-13. doi: 10.1016/j.thromres.2024.02.007. Epub 2024 Feb 13.
Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment.
To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment.
A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression.
770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min.
We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m, which are achieved by smaller dose reductions.
指南建议在 eGFR 分别为 15-29 和 30-60 ml/min 的患者中,将治疗性那屈肝素剂量(86 IU/kg)分别减少 50%和 25%。为了监测,建议测定峰值抗 Xa 水平。目前尚不清楚这是否会导致治疗性抗 Xa 水平,还是会导致抗 Xa 水平与无肾功能损害的患者相当。
确定肾功能损害患者中导致治疗性抗 Xa 水平的剂量范围,并确定导致无肾功能损害患者中通常出现的抗 Xa 水平的 86 IU/kg 剂量的百分比。
在五家医院进行了回顾性队列研究。纳入年龄≥18 岁、eGFR≥15 ml/min 的患者。纳入首次正确采集的峰值(即≥第三次给药后 3-5 小时,无论每位患者的剂量如何)。使用多元线性回归建立模拟预测模型。
共纳入 770 例患者。eGFR 和医院影响剂量与抗 Xa 水平之间的关系。峰值抗 Xa 水平为 0.75 IU/ml 时的剂量在不同医院之间有很大差异,eGFR 分别为 15-29、30-60 和>60 ml/min/1.73m 的患者中,剂量分别为 55-91、65-359 和 68-168 IU/kg。在 eGFR 15-29 和 30-60 ml/min/1.73m 的患者中,分别需要 86 IU/kg 的 75%和 91%的剂量,才能达到 eGFR>60 ml/min/1.73m 的患者的抗 Xa 水平。
只要实验室之间的抗 Xa 检测没有得到协调,并且没有验证抗 Xa 目标范围,我们就不建议基于抗 Xa 进行剂量调整。一种更好的方法可能是将目标水平设定为类似于 eGFR>60 ml/min/1.73m,这可以通过较小的剂量减少来实现。