Divisions of Hematology and Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
J Thromb Haemost. 2014 Sep;12(9):1554-7. doi: 10.1111/jth.12641. Epub 2014 Jul 15.
Enoxaparin is a frequently used anticoagulant in children. Unlike in adults, consensus guidelines recommend therapeutic monitoring to a target anti-factor Xa level of 0.5-1 U mL(-1) . Therapeutic ranges are not well correlated with clinical outcomes (e.g. thrombosis or hemorrhage), and assays are not standardized. Owing to limited reagent supplies, our clinical laboratory conducted a validation process and switched anti-FXa assays. Although the assays correlated well with each other, anti-FXa values were, on average, 33% higher with the new assay. The target anti-FXa range was not altered. We evaluated how this change in anti-FXa assays influenced enoxaparin dosing (mg kg(-1) ).
Enoxaparin dosing and anti-FXa values for all patients started on enoxaparin for the 6 months before and after assay change were retrospectively compiled and analyzed with a Student's t-test.
One hundred and nine children were started on enoxaparin before assay change, and 104 after assay change. The mean therapeutic enoxaparin dose (mg kg(-1) ) was significantly lower in subjects aged < 3 months (P = 0.01) and 3 months to 2 years (P < 0.0001), but not in subjects aged > 2 years (P = 0.18), after assay change. The median number of enoxaparin dose changes required to achieve the target range was significantly reduced after assay change, from 1 to 0 (P = 0.004).
The current pediatric practice of dose adjustment to achieve and maintain a target anti-FXa range is vulnerable to assay determination, which may provide false reassurance of efficacy and safety and represent misappropriation of time and resources. These data support a pediatric randomized controlled clinical trial comparing the safety and efficacy of enoxaparin weight-based dosing with or without dose titration based on anti-FXa.
依诺肝素是儿童中常用的抗凝剂。与成人不同，共识指南建议将目标抗因子 Xa 水平监测到 0.5-1 U mL(-1) 。治疗范围与临床结果（如血栓形成或出血）没有很好的相关性，并且检测方法也没有标准化。由于试剂供应有限，我们的临床实验室进行了验证过程并更换了抗 FXa 检测方法。尽管这些检测方法彼此相关性良好，但新检测方法的抗 FXa 值平均高出 33%。目标抗 FXa 范围没有改变。我们评估了抗 FXa 检测方法的这种变化如何影响依诺肝素的剂量（mg kg(-1) ）。
回顾性收集并分析了在检测方法改变前后 6 个月内开始使用依诺肝素的所有患者的依诺肝素剂量和抗 FXa 值，并使用学生 t 检验进行分析。
在检测方法改变之前，有 109 名儿童开始使用依诺肝素，在检测方法改变之后，有 104 名儿童开始使用依诺肝素。在年龄<3 个月（P=0.01）和 3 个月至 2 岁（P<0.0001）的患者中，治疗用依诺肝素剂量（mg kg(-1) ）明显较低，但在年龄>2 岁的患者中（P=0.18），剂量没有差异。在检测方法改变后，达到目标范围所需的依诺肝素剂量调整次数中位数显著减少，从 1 次减少至 0 次（P=0.004）。
目前，儿科调整剂量以达到和维持目标抗 FXa 范围的做法容易受到检测方法的影响，这可能会错误地保证疗效和安全性，并代表对时间和资源的不当利用。这些数据支持一项儿科随机对照临床试验，比较依诺肝素基于体重的剂量与或不基于抗 FXa 的剂量滴定的安全性和有效性。
