Franchini Massimo, Mannucci Pier Mannuccio
a Department of Transfusion Medicine and Hematology , Carlo Poma Hospital , Mantova , Italy.
b Angelo Bianchi Bonomi Hemophilia and Thrombosis Center , Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico and University of Milan , Milan , Italy.
Expert Opin Drug Saf. 2016 Oct;15(10):1391-400. doi: 10.1080/14740338.2016.1208747. Epub 2016 Jul 18.
The mainstay of treatment of hemophilia A and B is the replacement of the congenitally deficient coagulation factor through the intravenous infusion of specific concentrates (factor VIII, FVIII, in hemophilia A; factor IX, FIX, in hemophilia B). Several commercial brands of FVIII or FIX products extracted from human plasma or engineered using recombinant DNA technology are available.
We analyze the safety aspects of plasma-derived and recombinant FVIII and FIX products licensed in Europe, focusing on their pathogen safety and inhibitor and thrombosis risks. The safety aspects of bypassing agents (i.e., activated prothrombin complex concentrates and recombinant activated factor VII) used for treatment of bleeding episodes in inhibitor patients will be also briefly discussed.
The analysis of the published literature documents the high degree of safety from pathogen risk for both plasma-derived and recombinant products available for hemophilia treatment. The main threat to factor concentrate safety is represented by the development of neutralizing alloantibodies against the infused coagulation factor, which in hemophilia A seem to occur more frequently following the administration of recombinant than plasma-derived FVIII products. Great expectations are placed on newer products, particularly on those based upon mechanisms of action other than FVIII replacement.
甲型和乙型血友病治疗的主要方法是通过静脉输注特定浓缩物（甲型血友病输注凝血因子 VIII，FVIII；乙型血友病输注凝血因子 IX，FIX）来替代先天性缺乏的凝血因子。有几种从人血浆中提取或采用重组 DNA 技术制造的 FVIII 或 FIX 产品的商业品牌可供使用。
我们分析了在欧洲获批的血浆源性和重组 FVIII 及 FIX 产品的安全性，重点关注其病原体安全性、抑制剂和血栓形成风险。还将简要讨论用于治疗抑制剂患者出血发作的旁路制剂（即活化凝血酶原复合物浓缩物和重组活化因子 VII）的安全性。
对已发表文献的分析表明，用于血友病治疗的血浆源性和重组产品在病原体风险方面具有高度安全性。凝血因子浓缩物安全的主要威胁是针对输注的凝血因子产生中和性同种抗体，在甲型血友病中，使用重组 FVIII 产品后似乎比使用血浆源性 FVIII 产品更频繁地出现这种情况。人们对更新的产品寄予厚望，特别是那些基于 FVIII 替代以外作用机制的产品。
