Wiltrout Kayla, Lissick Jennifer, Raschka Mike, Nickel Amanda, Watson Dave
Department of Pharmacy (KW, JL, MR), Children's Minnesota, Minneapolis, MN.
Research Institute (DW, AN), Children's Minnesota, Minneapolis, MN.
J Pediatr Pharmacol Ther. 2020;25(8):689-696. doi: 10.5863/1551-6776-25.8.689. Epub 2020 Nov 13.
Enoxaparin has been studied for prophylaxis and treatment of thromboembolism in the pediatric population. Dose-finding studies have suggested higher mean maintenance dose requirements in younger children; however, the current recommended dosing schema endorsed by the American College of Chest Physicians remains conservative, likely secondary to limited data on the safety and efficacy of escalated starting doses. Primary objectives of this study included the identification of patient characteristics and risk factors with associations to anti-factor Xa (anti-Xa) values. The secondary objective was to determine an association between the initial anti-Xa value and thrombus resolution. Safety outcomes related to bleeding were also assessed.
This retrospective cohort study reviewed records of all pediatric patients ≤18 years of age who were initiated on therapeutic subcutaneous enoxaparin between October 1, 2008, and October 1, 2018, at Children's Hospitals and Clinics of Minnesota for an indication of incident thrombus (N = 283).
Successful resolution of thrombus was directly associated with attaining a therapeutic anti-Xa concentration upon first laboratory evaluation. Other characteristics with associations to initial anti-Xa values included age, body mass index, and certain diagnoses. The rate of composite bleeding was consistent across concentrations of anti-Xa (p = 0.4944).
Despite adherence to protocol, the current enoxaparin dosing nomogram is only successful at achieving a therapeutic anti-Xa concentration (0.5-1.0 unit/mL) 55.8% of the time. A more aggressive enoxaparin dosing nomogram is warranted, as delaying time to therapeutic anti-Xa values impacts clinical outcomes, specifically thrombus resolution. Further investigation into characteristics with association to anti-Xa concentrations is needed.
已对依诺肝素在儿科人群中预防和治疗血栓栓塞进行了研究。剂量探索研究表明年幼儿童的平均维持剂量需求更高；然而，美国胸科医师学会目前推荐的给药方案仍然较为保守，这可能是由于关于递增起始剂量的安全性和有效性的数据有限。本研究的主要目的包括确定与抗Xa因子（抗Xa）值相关的患者特征和危险因素。次要目的是确定初始抗Xa值与血栓溶解之间的关联。还评估了与出血相关的安全性结果。
这项回顾性队列研究回顾了2008年10月1日至2018年10月1日期间在明尼苏达儿童医院和诊所开始接受皮下注射依诺肝素治疗以治疗新发血栓的所有18岁及以下儿科患者的记录（N = 283）。
血栓的成功溶解与首次实验室评估时达到治疗性抗Xa浓度直接相关。与初始抗Xa值相关的其他特征包括年龄、体重指数和某些诊断。抗Xa各浓度下的复合出血率一致（p = 0.4944）。
尽管遵循了方案，但目前的依诺肝素剂量图表仅在55.8%的时间内成功达到治疗性抗Xa浓度（0.5 - 1.0单位/毫升）。由于延迟达到治疗性抗Xa值的时间会影响临床结果，特别是血栓溶解，因此需要一个更积极的依诺肝素剂量图表。需要进一步研究与抗Xa浓度相关的特征。
