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. Cooperative Study Groups

Br J Haematol. 1996 Sep;94(4):740-5. doi: 10.1046/j.1365-2141.1996.d01-1860.x.

Abstract

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 patient was infused with one dose of approximately 50 or 100 iu ristocetin cofactor activity (VWF:RiCoF) per kg body weight. Bleeding times were performed during the 24 h period after infusion. Plasma samples were obtained over the 96 h period after infusion and were analysed for factor VIII coagulant activity (FVIIIC), VWF:RiCoF, von Willebrand factor antigen (VWF:Ag), and multimers. The FVIIIC data were analysed by non-linear least-squares analysis assuming constant FVIIIC 'synthesis' and exponential decay. The VWF data were fitted for exponential decay. The average decay rates 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 100 iu VWF:RiCoF/kg than of 50 iu VWF:RiCoF/kg. Correction of the bleeding time was strongly dose dependent. At 4 h post infusion the median bleeding time was 9 min following a dose of 50 iu VWF:RiCoF/kg versus 3 min with a dose of 100 iu VWF:RiCoF/kg. There was no decrease in the bleeding time until the level of VWF:Ag or VWF:RiCoF reached > 100 u/dl.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bleeding Time
  • Child
  • Dose-Response Relationship, Drug
  • Factor VIII / biosynthesis
  • Factor VIII / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Ristocetin / pharmacology
  • von Willebrand Diseases / metabolism*
  • von Willebrand Factor / pharmacokinetics*

Substances

  • von Willebrand Factor
  • Ristocetin
  • Factor VIII