PHARMACOKINETICS OF VON-WILLEBRAND-FACTOR AND FACTOR-VIIIC IN PATIENTS WITH SEVERE VON-WILLEBRAND DISEASE (TYPE-3 VWD) - ESTIMATION OF THE RATE OF FACTOR-VIIIC SYNTHESIS

Nine patients (10 infusions) with a confirmed diagnosis of type 3 VWD were infused with von Willebrand factor (human), a preparation of von Willebrand factor (VWF) with a very low factor VIII content. Each pati ent was infused with one dose of approximately 50 or 100iu ristocetin cofactor activity (VWF:RiCoF) per kg body times were performed during the 24h period after infusion, Plasma samples were obtained over the 9 6h period after infusion and were analysed for factor VIII coagulant a ctivity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), a nd multimers, The FVIIIC data were analysed by non-linear least-square s analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay, The average decay rat es for FVIIIC. VWF:RiCoF and VWF:Ag were 0 . 041, 0 . 061 and 0 . 056 respectively. The average calculated 'synthesis' rate for FVIIIC was 6 . 4 u/dl/h. The synthesis of FVIIIC was slightly faster and the decay slightly slower following the infusion of 100iu VWF:RiCoF/kg than of 50iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose d ependent At 4h post infusion thp median bleeding time was 9 min follow ing a dose of 50iu VWF:RiCoF/kg versus 3 min with a dose of 100iu VWF: RiCoF/kg. There was no decrease in the bleeding time until the level o f VWF:Ag or VWF:RiCoF reached > 100 u/dl.