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Vox Sang. 2012 Jul;103(1):35-41. doi: 10.1111/j.1423-0410.2011.01576.x. Epub 2012 Jan 13.
We studied the structural and functional properties of von Willebrand factor (VWF) molecules present in a very high-purity plasma-derived factor VIII concentrate (VHP pdFVIII - Factane® ) because several observations suggest that the presence of VWF in factor VIII (FVIII) preparations may decrease their immunogenicity.
Ten marketed batches of VHP pdFVIII (Factane® ) with levels of VWF ranging from 15 to 39 IU/100 IU FVIII were analysed. The VWF multimeric pattern was studied by agarose gel electrophoresis. The binding of VWF to FVIII was studied by gel filtration and ELISA. The binding of VWF to GPIb was analysed by ELISA.
The results showed that high-molecular-weight multimers of VWF were present in VHP pdFVIII (Factane® ). VWF subunits maintain a triplet structure similar to that of normal plasma. Regardless of the VWF content, all FVIII molecules of each batch were co-eluted with VWF, and no free FVIII was detectable. By immunoassays, VWF was found to be able to bind to FVIII and platelet GPIb in a similar manner to that of VWF in normal plasma.
In all the VHP pdFVIII (Factane® ) batches studied, regardless of the level of VWF, the structure and capacity of VWF binding to FVIII and to platelet GPIb were fully preserved.
我们研究了高纯度血浆源性凝血因子 VIII 浓缩物（VHP pdFVIII-Factane®）中存在的血管性血友病因子（VWF）分子的结构和功能特性，因为有几项观察结果表明，VWF 在凝血因子 VIII（FVIII）制剂中的存在可能会降低其免疫原性。
分析了十种市售的高纯度血浆源性凝血因子 VIII 浓缩物（VHP pdFVIII-Factane®）批次，这些批次的 VWF 水平范围为 15 至 39IU/100IU FVIII。通过琼脂糖凝胶电泳研究 VWF 的多聚体模式。通过凝胶过滤和 ELISA 研究 VWF 与 FVIII 的结合。通过 ELISA 分析 VWF 与 GPIb 的结合。
结果表明，VHP pdFVIII（Factane®）中存在高分子量 VWF 多聚体。VWF 亚基保持与正常血浆相似的三聚体结构。无论 VWF 含量如何，每个批次的所有 FVIII 分子均与 VWF 共洗脱，并且无法检测到游离的 FVIII。通过免疫测定发现，VWF 能够以与正常血浆中 VWF 相似的方式结合 FVIII 和血小板 GPIb。
在所研究的所有 VHP pdFVIII（Factane®）批次中，无论 VWF 水平如何，VWF 与 FVIII 和血小板 GPIb 结合的结构和能力均得到了完全保留。
