重型血友病A患儿短期足量预防治疗及结束后非干预状态下的疗效观察

目的分析既往按需治疗的重型血友病A患儿接受短期足量预防治疗及结束后非干预状态下的出血情况及关节功能变化。方法对既往按需治疗的12例8.5岁(4~14岁)重型血友病A患儿,回顾性收集按需治疗3个月的出血情况,然后前瞻性观察短期足量预防治疗3个月(25 U/kg 3次/周)及非干预状态下治疗9个月的出血情况和关节功能HJHS评分,依据短期足量预防治疗结束后非干预状态下患儿的治疗方式分组分析。结果 12例患儿短期足量预防3个月的ABR(年化出血次数)及AJBR(年化关节出血次数)较既往基线状态按需治疗3个月明显减少(3.8±5.6次/年vs 64.3±13.9次/年;2.7±4.0次/年vs 39.6±18.6次/年,P0.05),HJHS总分在短期足量预防后下降62.0%。短期足量预防结束后9例按需治疗组的ABR及AJBR变化:结束后1~3月尚较基线按需治疗3个月减少(43.7±9.7次/年vs 58.6±9.8次/年;27.1±9.5次/年vs 34.7±12.0次/年,P0.05),但结束后4~6月则与基线按需治疗3个月类似(P0.05),HJHS总分在短期足量预防治疗结束后第3个月、第9个月分别较短期足量预防结束时回升35.5%及50.9%。短期足量预防结束后2例低量预防组的ABR/AJBR分别为4.8次/年及4.1次/年,短期足量预防结束后1例中量预防组则保持零出血。结论短期足量预防治疗能更明显减少重型血友病患儿的出血,但中断预防治疗3个月后ABR/AJBR将恢复到预防治疗前水平,且关节功能也会逐渐下降,说明持续预防治疗的重要性,提示持续中量预防治疗可能是中国现时资源有限的选择。

An Observation Study on Efficacy of Short-term Adequate-dose Prophylaxis and under Non-intervention after Prophylaxis in Children with Severe Hemophilia A

Objective To analyze bleeding conditions and the changes of joint function after short-term adequate-dose prophylaxis and under non-intervention in children with severe hemophilia A undergoing on-demand treatment previously .Methods Bleeding conditions were retrospectively collected from 12 children (mean age,8.5 years;age range,4-14 years)with severe hemophilia A undergoing on-demand treatment for 3 months previously .Then, bleeding conditions andHJHS score for joint function were prospectively observed after short-term adequate-dose prophylaxis (25 U/kg,3 times/w) for 3 months and treatment for 9 months under non-intervention .Children were grouped and analyzed based on treatment methods after short -term adequate-dose prophylaxis and under non-intervention.Results Among the 12 children,annualized bleeding rate( ABR) and annualized joint bleeding rate ( AJBR) after short-term adequate-dose prophylaxis for 3 months decreased significantly as compared with previous baseline state receiving on -demand treatment for 3 months (3.8 ±5.6 times/year vs 64.3 ±13.9 times/year;2.7 ±4.0 times/year vs 39.6 ±18.6 times/year,P <0.05 );HJHS total score reduced by 62.0% after short-term adequate-dose prophylaxis .After short-term adequate-dose prophylaxis ,the changes of ABR and AJBR in the on-demand treatment group ( n=9 ) were as follows:ABR and AJBR 1-3 months after prophylaxis significantly decreased as compared with baseline state receiving on-demand treatment for 3 months ( 43.7 ±9.7 times/year vs 58.6 ±9.8 times/year;27.1 ±9.5 times/year vs 34.7 ±12.0 times/year,P<0.05);while ABR and AJBR 4-6 months after prophylaxis weresimilar to baseline state receiving on-demand treatment for 3 months ( P>0.05 ) .HJHS total score at the 3 rd month and the 9 th month after short-term adequate-dose prophylaxis increased by 35.5% and 50.9%, respectively ,as compared with those immediately after short-term adequate-dose prophylaxis .In the low-dose prophylaxis group ( n=2 ) , ABR and AJBR after short-term adequate-dose prophylaxis were 4.8 times/year and 4.1 times/year,respectively.In the medium-dose prophylaxis group (n =1),no bleeding was detected after short-term adequate-dose prophylaxis .Conclusion Short-term adequate-dose prophylaxis can significantly reduce joint bleeding in children with severe hemophilia as compared with short -term medium/low-dose prophylaxis .However , ABR and AJBR recover to the levels before prophylaxis , and joint function declines gradually 3 months after prophylaxis.Therefore,prophylaxis needs to be continued,and continuous medium-dose prophylaxis may be a better choice under limited resources in China .