Mathieu Sophie, Crampe Carine, Dargaud Yesim, Lavigne-Lissalde Géraldine, Escuriola-Ettingshausen Carmen, Tardy Brigitte, Meley Roland, Thouvenin Sandrine, Stephan Jean L, Berger Claire
aHematology and Oncology Pediatric Unit, CHU Saint Etienne bHematology Laboratory, CHU Caremeau, Nimes cResearch Unit on Hemophilia, UFR Laennec dClinical Hemostasis Unit, Hôpital Edouard Herriot, Lyon eHemostasis Laboratory, CHU, Saint Etienne, France fHZRM - Hemophilia Centre Rhein Main, Frankfurt-Mörfelden, Germany.
Blood Coagul Fibrinolysis. 2015 Dec;26(8):940-5. doi: 10.1097/MBC.0000000000000300.
Severe hemophilia A is an X-linked bleeding disorder. Immune tolerance induction (ITI) is the best strategy of treatment when patients develop inhibitors. The objective is to illustrate the benefit of a high-purity human factor VIII/von Willebrand factor (VWF) concentrate (Octanate) in the management of ITI. We also wanted to raise the potential interest of laboratory assays such as thrombin-generation test (TGT) and epitope mapping. Two patients were treated during ITI, first with a recombinant FVIII and then with plasma-derived factor VIII without success, and, finally, with Octanate. Bypassing agents were used based on the results of TGT. Epitope mapping was performed during ITI therapy. These observations suggest the potential contribution of Octanate in the management of ITI in difficult cases. The use of bypassing agents can be necessary in prophylaxis or to treat bleedings, and may be guided by TGT results. Epitope mapping is used to describe the inhibitor. This article shows a decrease of the inhibitor directed against the C2 domain after initiation of Octanate. A high-purity human factor VIII/von Willebrand factor concentrate (Octanate) may be a valuable therapeutical option for ITI therapy. TGT and epitope mapping could be of help in the management of ITI.
重度甲型血友病是一种X连锁隐性出血性疾病。当患者产生抑制剂时，免疫耐受诱导（ITI）是最佳治疗策略。目的是阐明高纯度人凝血因子VIII/血管性血友病因子（VWF）浓缩物（Octanate）在ITI治疗中的益处。我们还想提高实验室检测如凝血酶生成试验（TGT）和表位作图的潜在应用价值。两名患者在ITI治疗期间，先用重组FVIII治疗，然后用血浆源性凝血因子VIII治疗均未成功，最后用Octanate治疗。根据TGT结果使用旁路制剂。在ITI治疗期间进行表位作图。这些观察结果提示Octanate在难治性病例的ITI治疗中可能有潜在作用。在预防或治疗出血时可能需要使用旁路制剂，且可根据TGT结果指导用药。表位作图用于描述抑制剂。本文显示Octanate开始使用后，针对C2结构域的抑制剂减少。高纯度人凝血因子VIII/血管性血友病因子浓缩物（Octanate）可能是ITI治疗的一种有价值的治疗选择。TGT和表位作图可能有助于ITI的治疗。
