Department of Pediatrics, Hotel-Dieu de France Hospital, Beirut, Lebanon.
Children's Hospital, Mohammed V. University, Rabat, Morocco.
Thromb Haemost. 2020 Jun;120(6):957-967. doi: 10.1055/s-0040-1710015. Epub 2020 May 11.
To date, the use of a fibrinogen concentrate (FC) administered in children with inherited fibrinogen deficiency is poorly documented. Treatment modalities may differ from those of adults. The aim of this study was to investigate the pharmacokinetics (PK), efficacy (bleeding/surgery) and safety of a triple-secured FC (FibCLOT, LFB, France) in young patients aged of 12 years or less.
This was a prospective, non-comparative, multicentre, phase 2-3 study. Estimated PK parameters were based on population PK modelling. Target fibrinogen levels were 1.2 and 1.0 g/L for major and minor events, respectively. In vivo recovery (IVR) was calculated at study entry to tailor the dose.
Sixteen afibrinogenaemia patients were treated with FC: 12 included in the PK study (6 aged ≤ 6 years and 6 aged 7-12 years). IVR at 1 hour post-infusion (geometric mean [coefficient of variation]) was 1.91 [20%] mg/dL per mg/kg and results were similar between the two age groups (1.87 [14%]) and (1.96 [27%]) with no statistical differences. Estimated half-life ( ) was 49.0 hours [12%] with no observed differences between groups (46.6 hours [10%] and 51.6 hours [12%]). Overall efficacy was rated as excellent/good in 96.9% of 32 bleeds and in 100% of 11 surgeries. Most of the events (39/43, 90.7%) were managed with one infusion. There was no serious adverse drug reaction.
Individually tailored dosing was efficacious in children who exhibited a lower IVR and shorter than those previously reported in adolescent and adult patients emphasising the importance of individualised dose optimisation.
迄今为止，在遗传性纤维蛋白原缺乏症儿童中使用纤维蛋白原浓缩物（FC）的情况记录甚少。治疗方式可能与成人不同。本研究旨在调查年龄在 12 岁或以下的年轻患者使用三重稳定纤维蛋白原（FibCLOT，LFB，法国）的药代动力学（PK）、疗效（出血/手术）和安全性。
这是一项前瞻性、非对照、多中心、2-3 期研究。基于群体 PK 模型估计 PK 参数。主要和次要事件的目标纤维蛋白原水平分别为 1.2 和 1.0g/L。在研究入组时计算体内回收率（IVR）以调整剂量。
16 名无纤维蛋白血症患者接受 FC 治疗：12 名患者纳入 PK 研究（6 名年龄≤6 岁，6 名年龄 7-12 岁）。输注后 1 小时 IVR（几何平均值[变异系数]）为 1.91[20%]mg/dL/每毫克/千克，两组之间结果相似（1.87[14%]）和（1.96[27%]），无统计学差异。估计半衰期（）为 49.0 小时[12%]，两组之间无观察到差异（46.6 小时[10%]和 51.6 小时[12%]）。32 次出血中有 96.9%（39/43）和 11 次手术中有 100%（11/11）的总体疗效评为极好/良好。大多数事件（39/43，90.7%）仅用一次输注即可处理。无严重药物不良反应。
个体化剂量调整在儿童中有效，这些儿童的 IVR 较低，半衰期较短，与以前在青少年和成年患者中报告的数据相比，这强调了个体化剂量优化的重要性。
