Qiu Shi-Qiu, Zhuang Jin-Mu, Zhou Xuan, Yin Rui-Xue, Liu Zhu-Qin, Ma Fei, Li Ying-Jia, Sun Jing
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2017 Oct 20;37(10):1391-1395. doi: 10.3969/j.issn.1673-4254.2017.10.18.
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.
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.
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).
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.
探讨接受低剂量和中剂量凝血因子VIII进行三级预防的成年重度甲型血友病（SHA）患者突破性出血的特征，并探索影响治疗效果的因素。
49例接受三级预防凝血因子VIII治疗的SHA患者（平均年龄31.53±7.33岁）被分为低剂量组（n = 15）和中剂量组（n = 34）。记录所有患者的临床出血表型（Pre-AJBR）、72小时凝血因子VIII谷值活性以及血友病功能独立性评分（FISH），并使用血友病管家应用程序记录出血事件和治疗数据。所有患者均随访至少6个月。
在低剂量组和中剂量组中，每年关节出血（AJBR）发作次数分别为18.79±13.03次和9.28±7.02次（P = 0.016），自发性出血比例分别为75.0%和47.7%。靶关节患者比例分别为80%和44%，靶关节出血发生率分别为59%和41%，预防性注射后0 - 12小时白内障出血发生率分别为4.86%和5.18%，中位突破性出血时间分别为40.08小时和46.08小时（P = 0.008）。两组中72小时凝血因子VIII谷值活性<1%的患者比例分别为44.4%和34.8%。在两组中，AJBR与预防性消耗剂量呈负相关（r = -0.57，P = 0.000，n = 49）以及FISH呈负相关，但与Pre-AJBR呈正相关（P<0.05）。
在中国成年SHA患者中，低剂量和中剂量凝血因子VIII的三级预防不足以实现预防关节疾病进展的目标。尽管预防剂量是影响治疗效果的最重要因素，但其他非剂量方法也可能有助于提高治疗效果。
