IN-VIVO CHARACTERIZATION OF RECOMBINANT VON-WILLEBRAND-FACTOR IN DOGSWITH VON-WILLEBRAND-DISEASE

Hereditary von Willebrand factor (VWF) deficiency in Dutch Kooiker dog s, which have undetectable levels of vWF, causes spontaneous hemorrhag e of mucosal surfaces similar to the clinical picture of von Willebran d disease in humans. Therefore, we used this canine model to study the in vivo effects of a new recombinant von Willebrand factor (rvWF) pre paration containing all species of VWF multimers compared with a rvWF fraction containing only low molecular weight multimers (LMW-rvWF) and with a plasma-derived factor VIII/vWF concentrate (pdvWF). In the vWF -deficient dogs, the half-life of vWF:Ag was 21.6 and 22.1 hours for r vWF, 7.7 hours for pdvWF, and 9 hours for LMW-rVWF; in vivo recovery o f vWF:Ag was 59%, 64%, and 70% for rvWF, 33% for pdvWF and 92% for LMW -rvWF; in vivo recovery of RCoF was 78%, 110%, and 120% for rvWF, and 25% for pdvWF. Both rvWF and pdvWF caused increases in factor VIII, wh ich were sustained even when vWF:Ag had decreased to nearly undetectab le levels and only monomeric or dimeric species were detectable on aga rose gels. At the dosages used, no effect was seen on bleeding time, b ut the rate of blood flow from cuticle wounds was reduced after a sing le bolus administration of rvWF. The rvWF was able to control a severe nose bleed in one dog. (C) 1997 by The American Society of Hematology .