Hematology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Haemophilia. 2022 Nov;28(6):e209-e218. doi: 10.1111/hae.14635. Epub 2022 Jul 18.
As standard care of severe haemophilia A (SHA), prophylaxis should be individualised.
This study aimed to investigate the effectiveness of this new-proposed individualised prophylaxis protocol.
Boys with SHA were enrolled and followed a PK-guided, trough-level escalating protocol of prophylaxis after a six-month observational period. In the next 2 years, clinical assessments including joint bleeds, ultrasound (US) scores and Haemophilia Joint Health Score (HJHS) in both sides of ankles, knees and elbows were conducted every 6 months as a scoring system, which determined whether the trough level's escalation. Adjustment of dosing regimen was based on WAPPS-Hemo.
Fifty-eight SHA boys were finally analysed. Their age and bodyweight were 5.3(2.8,6.9) years and 21.5(16,25) kg. During the study, 47 escalations were conducted. At study exit, the patient number and proportion of different trough level groups were: < 1 IU/dl, 17.2% (10/58); 1-3 IU/dl, 53.5% (31/58); 3-5 IU/dl, 15.5% (9/58); > 5 IU/dl, 13.8% (8/58). Significantly reduced annualised bleeding rate [4(0,8) to 0(0,2), p < .0001] and annualised joint bleeding rate [2(0,4) to 0(0,.25), p < .0001] was observed at study exit as well as the continuous trend of increased zero bleeding proportion (ZBP) (27.6%-69.0%) and zero joint bleeding proportion (46.5%-81.3%). Besides, 85% (6/7) of the target joints vanished. Statistical improvements of US scores (p = .04) and HJHS (p = .02) were also reported at study exit.
Our results showed the effectiveness of our protocol based on individualised target trough level and emphasise the importance of personalised prophylaxis.
作为重型血友病 A（SHA）的标准治疗方法，预防治疗应个体化。
本研究旨在探讨这种新提出的个体化预防方案的有效性。
入组的 SHA 男孩在经过 6 个月的观察期后，采用基于 PK 的、低谷浓度逐渐升高的预防方案。在接下来的 2 年内，每 6 个月对踝关节、膝关节和肘关节两侧进行一次临床评估，包括关节出血、超声（US）评分和血友病关节健康评分（HJHS），作为评分系统，决定低谷浓度的升高。剂量调整方案基于 WAPPS-Hemo。
最终分析了 58 名 SHA 男孩。他们的年龄和体重分别为 5.3（2.8，6.9）岁和 21.5（16，25）kg。在研究期间，进行了 47 次升级。在研究结束时，不同低谷浓度组的患者人数和比例分别为：<1IU/dl，17.2%（10/58）；1-3IU/dl，53.5%（31/58）；3-5IU/dl，15.5%（9/58）；>5IU/dl，13.8%（8/58）。研究结束时，年化出血率[4（0，8）至 0（0，2），p<0.0001]和年化关节出血率[2（0，4）至 0（0，0.25），p<0.0001]显著降低，零出血比例（ZBP）（27.6%-69.0%）和零关节出血比例（46.5%-81.3%）呈持续上升趋势。此外，85%（6/7）的目标关节消失。研究结束时，US 评分（p=0.04）和 HJHS（p=0.02）也有统计学上的改善。
我们的结果表明，基于个体化目标低谷浓度的方案是有效的，并强调了个体化预防的重要性。
