Niimi Kevin S, Fanning Jeffrey J
J Extra Corpor Technol. 2014 Mar;46(1):84-90.
Acquired antithrombin (AT) deficiency has been associated with patients on extracorporeal membrane oxygenation (ECMO) as a result of hemodilution, blood coagulation activation, and the use of heparin. Replacement of AT has been typically utilized through the use of fresh-frozen plasma or AT concentrate. Antithrombin alfa (ATryn) is a recombinant form of AT (rAT) with an identical amino acid sequence as that of plasma-derived antithrombin. The primary objective of this study is to examine the relationship of rAT dose to measured plasma antithrombin activity in a small series of patients who received rAT while on ECMO. A retrospective chart review was performed of all patients at Medical City Children's Hospital who received ATryn while supported on ECMO between December 2011 and April 2012. Five patients were identified and the patients' weight, bolus dose of ATryn, drip rate of ATryn, and AT blood levels were collected for analysis. The median age of these patients was 1 month (range, 1 day to 3.75 years). Because no dosing guidelines exist for pediatric ECMO, a starting dose of ATryn was chosen based on the manufacturer's labeled indication (prevention of thromboembolic events in patients with AT hereditary deficiency). The median dose of rAT was 368 IU/kg/day (range, 104-520 IU/kg/day) to obtain AT activity level of 80-120%. The average time to reach the targeted AT activity level (80-120%) was 12.7 hours (range, 11-17 hours). Our findings suggest that the published ATryn dose may be inadequate to reach desired AT activity concentrations for pediatric patients on ECMO. Difference in patient population, use of extracorporeal circuits, and the use of heparin are likely explanations for this finding. We would also recommend frequent checking of AT levels while delivering this drug because making timely adjustments is necessary for achieving and maintaining the target AT activity level.
获得性抗凝血酶（AT）缺乏与接受体外膜肺氧合（ECMO）治疗的患者相关，这是由于血液稀释、凝血激活以及肝素的使用所致。通常通过使用新鲜冷冻血浆或AT浓缩物来补充AT。抗凝血酶α（ATryn）是AT的重组形式（rAT），其氨基酸序列与血浆来源的抗凝血酶相同。本研究的主要目的是在一小部分接受ECMO治疗时接受rAT的患者中，研究rAT剂量与测量的血浆抗凝血酶活性之间的关系。对2011年12月至2012年4月期间在医疗城儿童医院接受ECMO支持时接受ATryn治疗的所有患者进行了回顾性病历审查。确定了5名患者，并收集了患者的体重、ATryn推注剂量、ATryn滴注速率和AT血液水平进行分析。这些患者的中位年龄为1个月（范围为1天至3.75岁）。由于儿科ECMO没有给药指南，基于制造商的标签适应症（预防AT遗传性缺乏患者的血栓栓塞事件）选择了ATryn的起始剂量。rAT的中位剂量为368 IU/kg/天（范围为104 - 520 IU/kg/天），以获得80 - 120%的AT活性水平。达到目标AT活性水平（80 - 120%）的平均时间为12.7小时（范围为11 - 17小时）。我们的研究结果表明，已公布的ATryn剂量可能不足以使接受ECMO治疗的儿科患者达到所需的AT活性浓度。患者群体差异、体外循环的使用以及肝素的使用可能是这一发现的原因。我们还建议在使用这种药物时频繁检查AT水平，因为及时调整对于达到和维持目标AT活性水平是必要的。
