Manchester University Department of Haematology, Manchester Royal Infirmary, Manchester, UK.
Blood. 2011 Jun 9;117(23):6367-70. doi: 10.1182/blood-2010-09-308668. Epub 2011 Apr 6.
The age-adjusted incidence of new factor VIII inhibitors was analyzed in all United Kingdom patients with severe hemophilia A between 1990 and 2009. Three hundred fifteen new inhibitors were reported to the National Hemophilia Database in 2528 patients with severe hemophilia who were followed up for a median (interquartile range) of 12 (4-19) years. One hundred sixty (51%) of these arose in patients ≥ 5 years of age after a median (interquartile range) of 6 (4-11) years' follow-up. The incidence of new inhibitors was 64.29 per 1000 treatment-years in patients < 5 years of age and 5.31 per 1000 treatment-years at age 10-49 years, rising significantly (P = .01) to 10.49 per 1000 treatment-years in patients more than 60 years of age. Factor VIII inhibitors arise in patients with hemophilia A throughout life with a bimodal risk, being greatest in early childhood and in old age. HIV was associated with significantly fewer new inhibitors. The inhibitor incidence rate ratio in HIV-seropositive patients was 0.32 times that observed in HIV-seronegative patients (P < .001). Further study is required to explore the natural history of later-onset factor VIII inhibitors and to investigate other potential risk factors for inhibitor development in previously treated patients.
本研究分析了 1990 年至 2009 年期间所有英国重度甲型血友病患者中新出现的第八因子抑制剂的发病率。在接受中位数（四分位距）为 12 年（4-19 年）随访的 2528 例重度甲型血友病患者中，有 315 例向国家血友病数据库报告了新的抑制剂。其中 160 例（51%）出现在中位数（四分位距）为 6 年（4-11 年）的 5 岁以上患者中。<5 岁患者新抑制剂的发生率为每 1000 个治疗年 64.29 例，10-49 岁患者为每 1000 个治疗年 5.31 例，而>60 岁患者显著升高（P =.01）至每 1000 个治疗年 10.49 例。甲型血友病患者在整个生命周期中均会出现第八因子抑制剂，且存在双峰风险，即儿童早期和老年时风险最大。HIV 与新抑制剂的发生显著相关。HIV 阳性患者的抑制剂发生率比值为 HIV 阴性患者的 0.32 倍（P <.001）。需要进一步研究来探索迟发性第八因子抑制剂的自然史，并研究其他潜在的治疗后患者抑制剂发生的危险因素。
