低中剂量凝血因子Ⅷ预防治疗重型血友病A患儿：关节综合评估及相关性分析

目的利用新的关节综合评估手段研究重型血友病A患儿凝血因子Ⅷ（FⅧ）低中剂量预防治疗的疗效。方法47例接受FⅧ治疗的重型血友病A患儿（FⅧ活性≤2%），其中18例低剂量预防治疗（FⅧ 10 U/kg，每周2~3次）、20例中剂量预防治疗（FⅧ15~30 U/kg，每周3次）和9例按需治疗（出血时根据血友病诊断与治疗中国专家共识标准输注FⅧ治疗）患儿。随访180 d，观察临床出血表型、关节结构、关节功能、活动能力四方面指标变化并进行相关性研究，使用Kruskal-Wallis、t检验及Spearman等级相关系数进行统计学分析，P<0.05为差异具有统计学意义。结果低中剂量预防治疗组均较按需治疗组明显改善临床出血表型（P<0.01），且中剂量预防治疗组改善优于低剂量预防治疗组（P<0.05）。而且在关节影像结构及功能综合评估方面，血友病关节健康评分（HJHS）总分变化、血友病功能独立性评分量表（FISH）总分变化，最严重单个靶关节彩超和同一最严重单个靶关节HJHS变化4个指标，低中剂量预防治疗组的变化值有明显小于按需治疗组的优势（均P<0.05），中剂量预防治疗组有可能有优于低剂量预防治疗组的趋势。重型血友病A患儿，年靶关节出血次数（ATJBR）与其彩超评分变化、ATJBR与其HJHS变化、年关节出血次数（AJBR）与FISH总分变化均无相关性（P>0.05）。结论FⅧ低中剂量预防治疗较按需治疗明显改善临床出血表型及延缓血友病患儿关节损伤的进展，但临床出血表型不足以全面反映病情进展。

Prophylactic treatment with low- and intermediate-dose factor VIII in children withsevere hemophilia A: comprehensive evaluation of joint outcomes and correlation analysis

Objective To study the effect of low- and intermediate-dose factor VIII (FVIII) for prophylactic treatment of severehemophilia A in children by comprehensively evaluating the outcomes of the joints. Methods Forty-seven children with severehemophilia A (FVIII activity ≤2%) were enrolled in this study. Eighteen of the children received prophylactic treatment withlow-dose FVIII (10 U/kg, 2-3 times a week), 20 received prophylactic treatment with intermediate-dose FVIII (15-30 U/kg, 3times a week), and 9 received on-demand treatment with FVIII infusion when bleeding occurred according to the ChineseExpert Consensus on the Diagnosis and Treatment of Hemophilia. The children were followed up for 180 days to observe thechanges in the indexes of clinical bleeding phenotype, joint structure, joint function, and joint mobility, and the correlation ofthese indexes were analyzed. Results Compared with on-demand treatment, prophylactic treatment with low- andintermediate-dose FVIII significantly improved the clinical hemorrhage phenotype (P<0.01), and the improvement wassignificantly more conspicuous with intermediate-dose prophylactic treatment (P<0.05). Comprehensive evaluation of the jointstructure and function changes showed that compared with on-demand treatment, prophylactic treatment with low- andintermediate-dose FVIII resulted in significant improvements in the total score of Hemophilia Joint Health Score (HJHS),Functional Independence Score in Hemophilia (FISH), the single most severe target joint ultrasound and HJHS score of thetarget joint (P<0.05) and prophylactic treatment with intermediate-dose FVIII appeared to produce better outcomes of the jointthan low-dose FVIII. No correlation was found between annual target joint bleeding rate (ATJBR) and ultrasound score,between ATJBR and HJHS change, or between annual joint bleeding rate (AJBR) and the total score of FISH (P>0.05).Conclusion Compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII cansignificantly improve the bleeding phenotype and delay the progression of joint injury, but the clinical hemorrhagic phenotypeis not sufficient to monitor the disease progression.