Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico and University of Milan, Milan, Italy.
J Thromb Haemost. 2012 May;10(5):781-90. doi: 10.1111/j.1538-7836.2012.04691.x.
Inhibitor development is influenced by several factors and the type of factor VIII (FVIII) products may play a role.
In order to explore such a role, we designed a cohort study whose novelty resides in the classification of products not only according to the source of FVIII (plasmatic, pd, or recombinant, r) but also to their degree of purity (expressed as specific activity).
PATIENTS/METHODS: Treatment data up to inhibitor development or 150 exposure days were collected in 377 patients with hemophilia A.
Inhibitors developed in 111 patients (29%; 96 high-responders, 25%). The cumulative incidence was progressively higher from patients treated with low/intermediate-purity pdFVIII compared with those treated with high-purity pd and rFVIII. The adjusted hazard ratio of inhibitor development was 4.9 with rFVIII and 2.0 with high-purity pdFVIII (95% CI, 2.9-8.3 and 1.1-4.0), taking as reference low/intermediate-purity pdFVIII. There was no difference in the frequency of inhibitor testing between treatment groups. Sensitivity analyses (in patients who never switched product type, previously untreated patients, those treated on-demand and those with high-risk F8 mutations) confirmed an increased inhibitor risk with rFVIII and high-purity pdFVIII.
This study shows that the degree of purity of FVIII products influences inhibitor development independently from other risk factors, and emphasizes that differences exist within pdFVIII products.
抑制剂的发展受到多种因素的影响，FVIII 产品的类型可能起作用。
为了探讨这种作用，我们设计了一项队列研究，其新颖之处在于不仅根据 FVIII（血浆、pd 或重组，r）的来源对产品进行分类，而且还根据其纯度（表示为比活度）进行分类。
患者/方法：在 377 名血友病 A 患者中收集了抑制剂发展或 150 次暴露日的治疗数据。
111 名患者（29%；96 名高反应者，25%）发生了抑制剂。与使用高纯度 pd 和 rFVIII 治疗的患者相比，使用低/中纯度 pdFVIII 治疗的患者抑制剂累积发生率逐渐升高。使用 rFVIII 和高纯度 pdFVIII 的抑制剂发展调整后的危险比分别为 4.9 和 2.0（95%CI，2.9-8.3 和 1.1-4.0），以低/中纯度 pdFVIII 为参考。治疗组之间抑制剂检测的频率没有差异。敏感性分析（在从未转换产品类型的患者、未治疗患者、按需治疗患者和具有高风险 F8 突变的患者中）证实 rFVIII 和高纯度 pdFVIII 增加了抑制剂的风险。
本研究表明 FVIII 产品的纯度独立于其他危险因素影响抑制剂的发展，并强调 pdFVIII 产品之间存在差异。
