重型血友病A患儿低剂量预防治疗血浆凝血因子Ⅷ谷浓度的检测

摘要

目的：对重型血友病A患儿低剂量预防治疗的血浆凝血因子Ⅷ(FⅧ)谷浓度进行测定,以探索血FⅧ的谷浓度水平与年化关节出血次数的相关性。方法对28例重型血友病患儿进行低剂量预防治疗(8~10 U/kg/次,2次/周,周二、周五的同一时间给药),前瞻性观察9个月(每3月为一期,共三期),分别检测各期用药后72 h及96 h(周二、周五给药前)血FⅧ的谷浓度,并将血FⅧ的谷浓度水平与年化关节出血总数、关节功能评分变化的相关性进行统计学分析。结果①用药后96 h血FⅧ的谷浓度28例患儿(占100%)全部在1．0%以下,用药72 h血FⅧ浓度22例(占78．6%)已降到1．0%以下,有6例患儿(占21．4%)仍能维持在1．0%以上,其中有4例(占14．2%)能达到2%以上。但是,100%的病例FⅧ的谷浓度无法达到3%。②低剂量预防治疗条件下,28例患儿年化关节出血数波动于4~15次。血FⅧ的谷浓度与年化关节出血数的散点图显示：达到1%以上的患儿,与谷浓度在1%以下的比较,年关节出血次数并无明显的下降趋势(P>0．05)。③用药72 h血FⅧ谷浓度>1．0%组,与<1．0%组相比,血友病患儿年化关节出血的次数(P>0．05),及关节HJHS评分的变化(P>0．05)均无显著性差异。结论①低剂量预防治疗,血友病患儿血FⅧ的谷浓度偏低,仍有较高的年化关节出血,提示低剂量预防方案可能剂量不足,无法达到预防的目的。②血友病患儿血FⅧ的谷浓度存在个体异质性,21．4%的患儿用药后72 h可达到1%以上,但FⅧ谷浓度与年化关节出血次数可能无相关性,应当探索每个患儿个性化的最适的血FⅧ谷浓度。%Objective The study aims to measure the plasma trough levels of coagulation factorⅧ( FⅧ) in severe hemophilia A children receiving low-dose prophylactic treatment,and explore its correlation with the annualized number of joint bleeding episodes. Methods This was a prospective observational study with a length of follow-up of 9 months(three months per phase,three phases in total). Low-dose recombinant FⅧwas administered at 8~10 U/kg twice weekly( at the same time on Tuesday and Friday respectively) as proph-ylactic treatment in 28 children with severe hemophilia A. During each of the three phases,blood tests were conducted before administration of FⅧ on a Tuesday and a Friday respectively,to measure the plasma trough levels of FⅧ72 hours and 96 hours after administration of the drug. Statistical analyses were executed to ex-amine the correlation of the plasma trough level of FⅧwith the annualized number of joint bleeding episodes and the Hemophilia Joint Health Score( HJHS). Results ①At 96 hours,the plasma trough level of FⅧfell below 1. 0%in all of the 28 pediatric patients(100%). At 72 hours the trough level had already dropped be-low 1. 0%in 22 patients(78. 6%);and the treatment was able to maintain a level above 1. 0% in only 6 pa-tients(21. 4%),of whom 4(14. 2%)had a level above2%. However,all patients were unable to achieve an FⅧtrough level of 3%.②Under the low-dose prophylactic treatment,the annualized number of joint bleeding episodes ranged between 4 and 15 in 28 patients. A scatter plot constructed to look for a relationship between the FⅧ trough level and the annualized number of joint bleeding episodes did not show a significant tendency of decrease for the annualized number in the patients achieving a level above 1%,as compared to those having a level below 1%(P>0. 05).③There were no significant differences in the annualized number of joint bleed-ing episodes( P>0. 05 ) and HJHS ( P >0. 05 ) between the >1. 0% group and the <1. 0 % group at 72 hours. Conclusion ① Low-dose prophylactic treatment appears not to lead to an ideal FⅧ trough level in children with hemophilia. A high annualized number of joint bleeding episodes still exist,suggesting that the insufficient dosage results in a low FⅧ trough level,which is unable to meet the objective of preventing joint bleeds.② Individual heterogeneity exists among hemophilia children in terms of the plasma FⅧtrough lev-el. Although 21. 4% of the patients can achieve a level above 1% 72 hours after administration of FⅧ,there could be no correlation between the FVIII trough level and annualized number of joint bleeding episodes. A personalized approach needs to be adopted to explore an optimal FⅧ trough level for individual patient.