title: 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.
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.
authors.affiliation: Biomedical Services, American Red Cross National Headquarters, Washington, D.C. USA.
authors.forename: D
authors.initials: D
authors.lastname: Menache
authors.forename: D L
authors.initials: DL
authors.lastname: Aronson
authors.forename: F
authors.initials: F
authors.lastname: Darr
authors.forename: R R
authors.initials: RR
authors.lastname: Montgomery
authors.forename: J C
authors.initials: JC
authors.lastname: Gill
authors.forename: C M
authors.initials: CM
authors.lastname: Kessler
authors.forename: J M
authors.initials: JM
authors.lastname: Lusher
authors.forename: P D
authors.initials: PD
authors.lastname: Phatak
authors.forename: A D
authors.initials: AD
authors.lastname: Shapiro
authors.forename: A R
authors.initials: AR
authors.lastname: Thompson
authors.forename: G C
authors.initials: GC
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001760:Bleeding Time; D002648:Child; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000096:biosynthesis / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012310:Ristocetin / Q000494:pharmacology; D014842:von Willebrand Diseases / Q000378:metabolism*; D014841:von Willebrand Factor / Q000493:pharmacokinetics*
chemical_list: D014841:von Willebrand Factor; D012310:Ristocetin; D005169:Factor VIII