Evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease

Dutch Kooiker dogs with hereditary von Willebrand disease have undetectable levels of von Willebrand factor (vWF), resulting in spontaneous haemorrhag e of mucosal surfaces similar to the clinical picture of von Willebrand dis ease in humans. We used this canine model of von Willebrand disease to stud y the in vivo effects of a new recombinant von Willebrand factor (rvWF) pre paration that contained all species of vWF multimers compared with a rvWF f raction containing only low molecular weight multimers (LMW-rvWF) and with a plasma-derived factor VIII/vWF concentrate (pdvWF). Administration of rvW F in these vWF-deficient dogs resulted in a vWF:Ag half-life of 21.6 h in o ne dog and 22.1 h in a second dog. Administration of pdvWF resulted in a ha lf-life for vWF:Ag of 7.7 h, and LMW-rvWF, 9 h. The in vivo recovery of vWF :Ag after administration of rvWF was 59%, 64% and 70% in three dogs, respec tively; 33% after pdvWF, and 92% after LMW-rvWF. The in vivo recovery of ri stocetin cofactor (RCoF) was 78%, 110% and 120% for rvWF, and 25% for pdvWF . Both rvWF and pdvWF caused increases in FVIII. Although no effect was see n on bleeding time at the dosages used, the rate of blood flow from cuticle wounds was reduced after a single bolus administration of rvWF. The rvWF w as able to control a severe nose bleed in one dog.