Fung Lela S, Klockau Christopher
Via Christi Regional Medical Center Wichita, Kansas.
J Pediatr Pharmacol Ther. 2010 Apr;15(2):119-25.
The objective of this dose range study is to expand on the relationship between age and weight-based doses of enoxaparin and resulting levels of anti-factor Xa (anti-Xa) in pediatric patients. The primary outcome of this study is to determine the average dose of enoxaparin required to produce a therapeutic effect. Secondary outcomes include the number of enoxaparin dose changes required to achieve a therapeutic level of anti-Xa in each age group, the success rates of achieving and maintaining therapeutic anti-Xa levels, and the effect of serum antithrombin concentrations on anti-Xa levels. The study will also determine whether different dispensed concentrations of enoxaparin play a role in achieving therapeutic levels of anti-Xa.
Single center, retrospective chart review. Patients were excluded from the study if they were older than 18 years of age, were receiving enoxaparin for prophylactic purposes, had a creatinine clearance < 30 ml/min/1.73m(2), and if no anti-factor Xa levels were drawn.
Average enoxaparin doses required for therapeutic levels of anti-factor Xa were 1.8 mg/kg for patients <1 month, 1.64 mg/kg (1 month to 1 year), 1.45 mg/kg (1 to 6 years), and 1.05 mg/kg (>6 years of age). An average of 3.24 dose changes was required for neonates to achieve therapeutic levels anti-factor Xa. The success rates for achieving and maintaining therapeutic levels were both 41%. Patients with low serum antithrombin levels were more likely to have low anti-Xa levels than those with normal or high values, 52% vs 40% vs 18%, respectively. Patients receiving diluted concentrations, 10 or 20 mg/mL, experienced lower anti-Xa levels than patients who received the standard manufactured concentration of 100 mg/mL, 61% vs 33%.
Based on this dose-range study, enoxaparin should be initiated at larger doses than recommended by the current guidelines to promptly achieve therapeutic anti-Xa levels. Doses should be divided into three age groups instead of two as currently suggested in the guidelines. To increase the likelihood of achieving therapeutic levels, the commercially available enoxaparin product should not be diluted if possible.
本剂量范围研究的目的是进一步探讨儿科患者中依诺肝素基于年龄和体重的剂量与抗Xa因子(抗Xa)水平之间的关系。本研究的主要结果是确定产生治疗效果所需的依诺肝素平均剂量。次要结果包括每个年龄组达到抗Xa治疗水平所需的依诺肝素剂量变化次数、达到并维持抗Xa治疗水平的成功率以及血清抗凝血酶浓度对抗Xa水平的影响。该研究还将确定不同剂型浓度的依诺肝素在达到抗Xa治疗水平方面是否起作用。
单中心回顾性病历审查。如果患者年龄超过18岁、接受预防性依诺肝素治疗、肌酐清除率<30 ml/min/1.73m²以及未检测抗Xa因子水平,则将其排除在研究之外。
抗Xa因子治疗水平所需的依诺肝素平均剂量,小于1个月的患者为1.8 mg/kg,1个月至1岁为1.64 mg/kg,1至6岁为1.45 mg/kg,大于6岁为1.05 mg/kg。新生儿平均需要3.24次剂量调整才能达到抗Xa因子治疗水平。达到和维持治疗水平的成功率均为41%。血清抗凝血酶水平低的患者比正常或高值患者更有可能出现低抗Xa水平,分别为52%、40%和18%。接受稀释浓度(10或20 mg/mL)的患者的抗Xa水平低于接受标准生产浓度(百毫克/mL)的患者,分别为61%和33%。
基于本剂量范围研究,依诺肝素的起始剂量应高于现行指南推荐的剂量,以便迅速达到抗Xa治疗水平。剂量应分为三个年龄组,而不是现行指南建议的两个年龄组。为提高达到治疗水平的可能性,市售依诺肝素产品应尽可能不稀释。