重组凝血因子与血源凝血因子的分子差异及其对药理药效学的影响

Molecular differences between recombinant coagulation factors and plasmaderived coagulation factors,and their effects on pharmacology and efficacy

重组凝血因子面世以来,在凝血因子缺陷和相关适应证患者中达到了良好的防治效果,已经开始替代血源凝血因子制品。然而,重组制品在免疫原性和抑制物产生方面的不足也受到关注。本文对几种主要的重组凝血因子与血源凝血因子的结构差异进行了综述,包括分子序列和翻译后修饰的多种形式等,并探讨这些结构上的差异对药理学、药效学和药代动力学的可能影响。这些分子差异和机制的揭示有助于探索和改进重组凝血因子的产量和质量,具有积极的临床治疗意义。

Since their successful launch, the recombinant coagulation factors have been effective in the treatment and prophylaxis of respective deficiencies, and started to replace plasma-derived coagulation factors. However, immunogenieity and induction of inhibitors associated with the uses of these recombinant products have drawn certain attention. This manuscript reviews the structural differences between several major recombinant coagulation factors and their plasma-derived counterparts, including sequences and many forms of post-translational modifications, and discusses the possible effects of these structural differences on the pharmacology, efficacy and pharmacokinetics of the products. The demonstration of structural differences and underlying mechanisms helps to improve the production yield and quality of recombinant coagulation factors, which is of significant clinical importance.