• FVIII immunogenicity;
  • haemophilia A;
  • very high-purity FVIII;
  • von Willebrand factor

Background and Objectives  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.

Materials and Methods  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.

Results  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.

Conclusions  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.