Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted ma...Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health issues.The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs.Additionally,we aimed to investigate the mental health status of HCs in China.Methods:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this study.Long distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or F9.Coagulation factor activity was detected by a one-stage clotting assay.The Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental health.Results:A total of 90.6%of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,respectively.The median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3%of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8%(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding phenotype.The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7%of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and severe.The pooled estimates of all nine factors were significantly higher than those in the general population(P<0.05).Conclusions:The detection rate of gene mutations in hemophilia mothers was 90.6%,with a median clotting factor level of 0.74 IU/mL,and 14.3%of HCs had a clotting factor level of 0.40 IU/mL or below.A history of bleeding was present in 41.2%of HCs with low clotting factor levels(less than 0.50 IU/mL).Additionally,given the fragile mental health status of HCs in China,it is critical to develop efficient strategies to improve psychological well-being.展开更多
本文于2023年09月发表于《Blood》杂志,发表后引起业内广泛关注,在Blood Podcast(Episode 12 Season 6,https://ashpublications.org/blood/pages/blood_podcast)重点介绍并同期发布了述评文章(Roger J.S.Preston,2023,9,21)。本文文章...本文于2023年09月发表于《Blood》杂志,发表后引起业内广泛关注,在Blood Podcast(Episode 12 Season 6,https://ashpublications.org/blood/pages/blood_podcast)重点介绍并同期发布了述评文章(Roger J.S.Preston,2023,9,21)。本文文章题录为:Miao Jiang,Fei Yang,Yizhi Jiang,et al.Safety and efficacy of an anti-human APC antibody for prophylaxis of congenital factor deficiencies in preclinical models[J].Blood,2023,142(12):1071-1081.该研究基于先前发表的鼠抗体HAPC1573进行工程改造,获得一种可选择性阻断人活化蛋白C(APC)的抗凝活性而不影响APC细胞保护功能的人源化抗体SR604,并验证了其治疗先天性因子缺乏的安全性和有效性。该研究为先天性凝血因子缺乏患者提供了通过抑制内源性抗凝途径,使体内凝血系统与抗凝系统实现“再平衡”的新治疗策略。经通讯作者许可,再次通过佳文解读的方式来阐述这一研究。展开更多
目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻...目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻和常温孵育15 min、30 min、1和2 h及37℃孵育30 min、1和2 h APTT纠正试验。结果:APTT纠正试验结果与凝血因子Ⅷ抑制物滴度呈明显的相关性,ROC曲线下37℃孵育2 h APTT纠正试验判断有无凝血因子Ⅷ抑制物最佳诊断界点是43.8 s(敏感度85.90%,特异度100%),区分高滴度与低滴度Ⅷ抑制物的最佳诊断界点为52.4 s(敏感度98.18%,特异度95.65%)。即刻APTT无法纠正的临界凝血因子Ⅷ抑制物滴度为5.14 BU/ml,37℃孵育2 h APTT不能纠正对应的凝血因子Ⅷ抑制物的滴度为1.31 BU/ml。对不同时间和温度下APTT纠正试验结果进行配对t检验,差异有统计学意义(P<0.05)。结论:APTT纠正试验结果可作为凝血因子Ⅷ抑制物的筛查指标,较低Ⅷ抑制物滴度时呈明显的对温度-时间的依赖性,血友病患者即刻APTT无法纠正则应警惕较高滴度凝血因子Ⅷ抑制物存在的可能。展开更多
基金supported by Pfizer and the Haemophilia,Experience,Results,and Opportunities(HERO)Research Grant(Novo Nordisk).
文摘Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health issues.The purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of HCs.Additionally,we aimed to investigate the mental health status of HCs in China.Methods:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this study.Long distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or F9.Coagulation factor activity was detected by a one-stage clotting assay.The Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental health.Results:A total of 90.6%of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,respectively.The median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3%of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8%(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding phenotype.The total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7%of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and severe.The pooled estimates of all nine factors were significantly higher than those in the general population(P<0.05).Conclusions:The detection rate of gene mutations in hemophilia mothers was 90.6%,with a median clotting factor level of 0.74 IU/mL,and 14.3%of HCs had a clotting factor level of 0.40 IU/mL or below.A history of bleeding was present in 41.2%of HCs with low clotting factor levels(less than 0.50 IU/mL).Additionally,given the fragile mental health status of HCs in China,it is critical to develop efficient strategies to improve psychological well-being.
文摘本文于2023年09月发表于《Blood》杂志,发表后引起业内广泛关注,在Blood Podcast(Episode 12 Season 6,https://ashpublications.org/blood/pages/blood_podcast)重点介绍并同期发布了述评文章(Roger J.S.Preston,2023,9,21)。本文文章题录为:Miao Jiang,Fei Yang,Yizhi Jiang,et al.Safety and efficacy of an anti-human APC antibody for prophylaxis of congenital factor deficiencies in preclinical models[J].Blood,2023,142(12):1071-1081.该研究基于先前发表的鼠抗体HAPC1573进行工程改造,获得一种可选择性阻断人活化蛋白C(APC)的抗凝活性而不影响APC细胞保护功能的人源化抗体SR604,并验证了其治疗先天性因子缺乏的安全性和有效性。该研究为先天性凝血因子缺乏患者提供了通过抑制内源性抗凝途径,使体内凝血系统与抗凝系统实现“再平衡”的新治疗策略。经通讯作者许可,再次通过佳文解读的方式来阐述这一研究。
文摘目的:分析凝血因子Ⅷ抑制物阳性血友病患者APTT纠正试验结果,提高APTT纠正试验在凝血因子Ⅷ抑制物筛查中的价值。方法:收集并稀释制备不同滴度凝血因子Ⅷ抑制物血浆80份进行常规的即刻及37℃孵育2 h APTT纠正试验,选取15份样本进行即刻和常温孵育15 min、30 min、1和2 h及37℃孵育30 min、1和2 h APTT纠正试验。结果:APTT纠正试验结果与凝血因子Ⅷ抑制物滴度呈明显的相关性,ROC曲线下37℃孵育2 h APTT纠正试验判断有无凝血因子Ⅷ抑制物最佳诊断界点是43.8 s(敏感度85.90%,特异度100%),区分高滴度与低滴度Ⅷ抑制物的最佳诊断界点为52.4 s(敏感度98.18%,特异度95.65%)。即刻APTT无法纠正的临界凝血因子Ⅷ抑制物滴度为5.14 BU/ml,37℃孵育2 h APTT不能纠正对应的凝血因子Ⅷ抑制物的滴度为1.31 BU/ml。对不同时间和温度下APTT纠正试验结果进行配对t检验,差异有统计学意义(P<0.05)。结论:APTT纠正试验结果可作为凝血因子Ⅷ抑制物的筛查指标,较低Ⅷ抑制物滴度时呈明显的对温度-时间的依赖性,血友病患者即刻APTT无法纠正则应警惕较高滴度凝血因子Ⅷ抑制物存在的可能。
