The Israeli National Hemophilia Center, Tel Hashomer Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.
Haemophilia. 2011 Jul;17(4):625-9. doi: 10.1111/j.1365-2516.2010.02464.x. Epub 2011 Feb 7.
Recent reports have raised concerns regarding potential risk factors for inhibitor development. In Israel, all haemophilia patients (n = 479) are followed by the National Hemophilia Center. Most children are neonatally exposed to factor concentrate (due to circumcision performed at the age of 8 days). The impact of early exposure and recombinant FVIII products (rFVIII) administration (approved in Israel since 1996) upon inhibitor occurrence in our cohort of haemophilia A (HA) patients was analysed. Two hundred ninety-two consecutive paediatric cases with a first symptomatic onset of HA were enrolled and followed over a median time of 7 years [min-max: 9 months to 17 years]. Study endpoint was inhibitor development against factor VIII. In addition, the treatment regimens applied, i.e. bolus administration or 'continuous infusion' and the family history of inhibitor development were investigated. During the follow-up period 31/292 children (10.6%) developed high titre inhibitors. Inhibitors occurred in 14/43 (32.5%) HA patients neonatally exposed to rFVIII, as compared to 22/249 previously treated with Plasma Derived (PD) products (8.8%). The odds ratio for inhibitor formation in rFVIII treated HA patients was 3.43 (95% CI: 1.36-8.65). Transient inhibitor evolved among 2/43 paediatric HA patients, only among those treated with rFVIII. The risk of inhibitor detection significantly increased among HA children treated by continuous infusion (P = 0.025). Our experience shows that the risk of inhibitor formation may be increased by early exposure to recombinant concentrates. The multiple variables affecting inhibitor incidence deserve further attention by larger prospective studies.
最近的报告引起了人们对抑制剂发展的潜在风险因素的关注。在以色列，所有血友病患者（n = 479）都由国家血友病中心进行随访。大多数儿童在出生后第 8 天因割礼而接触到因子浓缩物（由于因子浓缩物）。分析了我们的血友病 A（HA）患者队列中早期暴露和重组 FVIII 产品（rFVIII）给药（自 1996 年在以色列批准）对抑制剂发生的影响。纳入了 292 例连续儿科病例，这些病例首次出现 HA 症状，中位随访时间为 7 年[最短-最长：9 个月至 17 年]。研究终点是针对因子 VIII 的抑制剂发展。此外，还研究了所应用的治疗方案，即推注给药或“连续输注”以及抑制剂发展的家族史。在随访期间，31/292 名儿童（10.6％）发展为高滴度抑制剂。在接受 rFVIII 治疗的 14/43 例（32.5％）HA 患者中发生了抑制剂，而在先前接受血浆衍生（PD）产品治疗的 22/249 例（8.8％）中发生了抑制剂。接受 rFVIII 治疗的 HA 患者中抑制剂形成的优势比为 3.43（95％CI：1.36-8.65）。仅在接受 rFVIII 治疗的 2/43 名儿科 HA 患者中，有 2 名患者发生了短暂抑制剂。接受连续输注治疗的 HA 儿童中，抑制剂检测的风险显着增加（P = 0.025）。我们的经验表明，早期接触重组浓缩物可能会增加抑制剂形成的风险。需要更大的前瞻性研究进一步关注影响抑制剂发生率的多个变量。
