目的 研究中国重型血友病A成人患者低中剂量三级预防治疗的突破性出血特点及其影响因素.方法49例患者(31.53± 7.33岁)按照预防剂量分为低剂量组和中剂量组;评估临床出血表型(Pre-AJBR)、72 hFⅧ谷活性、活动能力(FISH评分),利用"血友管家"APP前瞻性记录出血与治疗情况,中位随访6月.结果 低剂量组15例;中剂量组34例;低剂量组和中剂量组关节突破性出血(AJBR)为18.79±13.03次/年和9.28±7.02次/年(P=0.016),自发性出血比例为75.0%和47.7%,存在靶关节患者比例为80%和44%,靶关节出血占比为59%和41%,中位突破性出血出现时间为预防注射后40.08 h和46.08 h(P=0.008),预防注射后0~12 h突破性出血发生率为4.86%和5.18%,72 hFⅧ谷活性<1%比例为44.4%和34.8%;AJBR与预防消耗因子量负相关(r=-0.57,P=0.000,n=49);两组AJBR均与FISH评分负相关,与Pre-AJBR正相关(P<0.05).结论 低中剂量三级预防治疗尚无法使多数中国重型血友病A成人患者获得阻止关节病变进展的目标;因子剂量虽是预防疗效的最主要影响因素,但通过非因子途径也可能改善疗效.%Objective To investigate the characteristics of breakthrough bleeding in adult patients with severe hemophilia A (SHA)receiving low-and intermediate-dose FVIII for tertiary prophylaxis and explore the factors affecting the outcomes of the treatment.Methods Forty-nine patients(mean age 31.53±7.33 years)with SHA receiving tertiary prophylaxis FVIII treatment were divided into low-dose group(n=15)and intermediate-dose group(n=34).The data including clinical bleeding phenotype (Pre-AJBR), 72 h FVIII trough activity, and Functional Independence Score in Hemophilia (FISH) were recorded in all the patients,and Hemophilia Steward APP was used to record the bleeding episode and the treatment data.All the patients were followed up for at least 6 months.Results In the low-dose and intermediate-dose groups,the number of joint bleeding(AJBR) episodes were 18.79 ± 13.03 and 9.28 ± 7.02 per year (P=0.016), and the proportions of spontaneous bleeding were 75.0% and 47.7%,respectively.The proportions of patients with target joint were 80% and 44%,target joint bleeding occurred in 59% and 41%, and cataract bleeding after 0-12 h of prophylactic injection occurred in 4.86% and 5.18% of the patients with a median breakthrough bleeding time of 40.08 h and 46.08 h(P=0.008),respectively.The proportions of patients with 72 h FVIII trough activity<1% were 44.4% and 34.8% in the two groups,respectively.AJBR was negatively correlated with the preventive dose consumed(r=-0.57,P=0.000,n=49)and FISH,but positively correlated with Pre-AJBR in the two groups(P<0.05).Conclusion Tertiary prophylaxis with low-and intermediate-dose FVIII is not sufficient to achieve the goal of preventing progression of joint disease in Chinese adult patients with SHA.Although the prophylactic dose is the most important factor to affect the treatment efficacy,other non-factor approaches may also help to improve the efficacy of the treatment.
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