Department of Cell Therapy and Hematology, Hemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy.
Haemophilia. 2013 Sep;19(5):686-90. doi: 10.1111/hae.12158. Epub 2013 Apr 22.
The prevalence of inhibitors in haemophilia B is significantly lower than that of patients with haemophilia A. However, the peculiar occurrence of allergic reactions associated with the onset of inhibitor in haemophilia B (HB) may render immune tolerance a risky procedure. We have carried out a detailed survey among all the Italian Hemophilia Centers to analyse all the patients with HB and inhibitors. A total of eight patients were reported among 282 living patients (2.8%) with severe factor IX (FIX) deficiency (FIX < 1 U dL(-1)). In addition, two deceased patients were also identified. Six patients carried nonsense mutations while in four partial or complete gene deletions were detected. Three patients (one deceased) had history of allergic/anaphylactic reaction upon substitutive treatment, which in one case was recurrent and resolved after switching to plasma derived FIX. Immune tolerance was adopted in five patients and in four complete response was achieved while in the remaining it was partial. No nephrotic syndrome was observed. Our data confirm that inhibitors in HB occur in patients with null mutations or complete/partial gene deletion. Immune tolerance can be achieved also in HB patients, without allergic reactions or nephrotic syndrome upon replacement therapy.
乙型血友病患者抑制剂的发生率明显低于甲型血友病患者。然而，乙型血友病（HB）抑制剂发病时与过敏反应相关的特殊发生情况可能使免疫耐受成为一种危险的程序。我们对所有意大利血友病中心进行了详细调查，以分析所有 HB 和抑制剂患者。在 282 名严重因子 IX（FIX）缺乏症（FIX < 1 U dL(-1)）的存活患者中，共报告了 8 名患者（2.8%）。此外，还发现了两名已故患者。6 名患者携带无意义突变，而在 4 名患者中检测到部分或完全基因缺失。3 名患者（1 名已故）在替代治疗时有过敏/过敏性反应史，其中 1 例为复发性，在改用血浆源性 FIX 后得到缓解。5 名患者采用免疫耐受治疗，4 名患者完全缓解，其余患者部分缓解。未观察到肾病综合征。我们的数据证实，HB 抑制剂发生在无义突变或完全/部分基因缺失的患者中。免疫耐受也可在 HB 患者中实现，在替代治疗时无过敏反应或肾病综合征。
