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.
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.
Menache
D
D
Biomedical Services, American Red Cross National Headquarters, Washington, D.C. USA.
Aronson
D L
DL
Darr
F
F
Montgomery
R R
RR
Gill
J C
JC
Kessler
C M
CM
Lusher
J M
JM
Phatak
P D
PD
Shapiro
A D
AD
Thompson
A R
AR
White
G C
GC
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*
D014841:von Willebrand Factor; D012310:Ristocetin; D005169:Factor VIII