Abstract:

Objective　To evaluate the number of annual bleeding and annual joint bleeding and safety of third-generation full length recombinant human coagulation factor Ⅷ（ADVATE） in the prophylactic treatment of childhood patients with moderate-to-severe hemophilia A. Methods　Fifteen children aged from 5 to 18 years with moderate-to-severe hemophilia A were enrolled in the one center，prospective，nonrandom，self-control study from Nov.01，2014 to Nov.30，2016. Children were treated with one-year long-course infusion of ADVATE with a dose of 20～40 U/kg twice-weekly or three times weekly. The numbers of annual bleeding and annual joint bleeding after the prophylaxis treatment were compared with that on-demand. Moreover，any adverse effect and serious adverse reaction related to ADVATE usage were documented during the study. The FⅧ inhibitor titer were measured with modified Nijmegen method before and after the prophylaxis every 3 to 6 months. Results　The FⅧ∶C for these 15 boys，median age 15，was less than 2.2%，with 8 patient severe type. The number of annual bleeding was reduced from（27.60±13.67） on-demand treatment to（2.57±1.36） after the prophylaxis treatment（P＜0.001），and the number of annual joint bleeding was also reduced from（11.13±8.81） to（0.93±1.10）（P＜0.001）. Seven patients had zero annual joint bleeding the mean annual bleeding for mild，moderate and severe degree was decreased significantly with zero times for severe degree bleeding after the prophylactic treatment. No adverse effect or serious adverse reaction related to ADVATE was recorded during one-year period treatment and FⅧ inhibitor detection was negative. Conclusion　Prophylactic treatment with ADVATE can effectively decrease the annual bleeding and annual joint bleeding in children with moderate-to-severe hemophilia A. This therapy is safe with FⅧ inhibitor test negative.

Key words: hemophilia A, prophylactic treatment, recombinant human coagulation factor Ⅷ, ADVATE

摘要：

目的    评估第三代全长链重组凝血因子Ⅷ（fLFⅧ）预防治疗中间型、重型血友病A患儿的年出血次数、关节年出血次数和安全性。方法    2014-11-01—2016-11-30采用单中心、前瞻、非随机、自身对照比较南京大学医学院附属鼓楼医院血液科应用fLFⅧ进行大剂量预防治疗1年后的中间型、重型血友病A患儿年出血次数、关节年出血次数、凝血因子Ⅷ（FⅧ）抑制物的改变及药物副反应。结果    15例患儿均为男性，年龄中位数15岁（5～18岁），所有患儿FⅧ活性（FⅧ∶C）＜2.2%，其中，重型血友病A 8例。应用fLFⅧ 20～40 U/kg、每周2～3次进行大剂量预防治疗1年，年出血次数由（27.60±13.67）次降为（2.57±1.36）次（P＜0.001），减少了90.7%；关节年出血次数由（11.13±8.81）次降为（0.93±1.10）次（P＜0.001），减少了91.6%。7例经大剂量预防治疗达到关节年出血0次。不同程度的年出血次数均下降，其中重度年出血次数下降为0次。所有患儿在进行大剂量预防治疗1年间未发生药物相关副反应或严重不良反应，FⅧ抑制物滴度检测有3例0.1 BU/mL，其余未检出。结论    应用fLFⅧ进行大剂量预防治疗可有效降低中间型、重型血友病A患儿年出血次数和关节年出血次数，安全、无副反应，无抑制物产生。

关键词: 血友病A, 预防治疗, 重组凝血因子, 百因止