Relationships between factor VIII:Ag and factor VIII in recombinant and plasma‐derived factor VIII concentrates Journal Articles uri icon

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abstract

  • Summary.  A variety of plasma‐derived (pd) and recombinant (r) factor VIII (FVIII) concentrates are used to prevent and treat bleeding in severe hemophilia A patients. A significant side effect of FVIII replacement is the development of FVIII neutralizing antibodies (inhibitors) in up to 30% of patients receiving FVIII concentrates. The FVIII protein content (FVIII:Ag) per unit of FVIII:C in FVIII concentrates, and how effectively the FVIII:Ag in FVIII concentrates binds to von Willebrand factor (VWF) may provide information relevant for the survival of FVIII:C in vivo and for estimating the risk for inhibitor development. The FVIII:Ag content of nine r‐FVIII and nine pd‐FVIII concentrates were quantified in this study using two enzyme‐linked immunosorbent assay (ELISA) platforms. The two ELISA platforms were based on the use of a monoclonal anti‐(FVIII light chain)‐IgG and polyclonal anti‐FVIII antibodies as capture antibodies and both ELISAs were equally able to detect ≥0.005 IU of FVIII:Ag. Measured in international units, the r‐FVIII concentrates contained significantly higher FVIII:Ag per unit of FVIII:C than the pd‐FVIII concentrates. The VWF‐binding profiles of the r‐FVIII and pd‐FVIII concentrates were also determined by gel filtration chromatography. Unlike the plasma‐derived products, the r‐FVIII concentrates invariably contained a fraction of FVIII:Ag molecules (∼20%) which was unable to associate with VWF. Given that VWF regulates both factor VIII proteolysis and survival of FVIII:Ag in vivo, the fraction of FVIII:Ag unable to bind to VWF may have a reduced survival and be more susceptible to proteolytic degradation in vivo. The extent to which the fractions of FVIII:Ag in concentrates able and unable to bind to VWF contribute to inhibitor development in severe FVIII‐deficient patients is unknown.

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publication date

  • September 2004