Preclinical evaluation of recombinant von Willebrand factor in a canine model of von Willebrand disease

Dutch Kooiker dogs with hereditary von Willebrand disease (vWD) have undete ctable levels of von Willebrand factor (vWF), resulting in spontaneous hemo rrhage of mucosal surfaces similar to the clinical picture of vWD in humans . We used this canine model of vWD to study the in vivo effects of a new re combinant von Willebrand factor (rvWF) preparation that contained all speci es of vWF multimers compared with an rvWF fraction containing only low mole cular weight multimers (LMW-rvWF) and with a plasma-derived factor VIII/vWF concentrate (pdvWF). Administration of rvWF in these vWF-deficient dogs re sulted in a vWF:Ag half-life of 21.6 hours in one dog and 22.1 hours in a s econd dog. Administration of pdvWF resulted in a half-life for vWF:Ag of 7. 7 hours, and LMW-rvWF, 9 hours. The in vivo recovery of vWF:Ag after admini stration of rvWF was 59, 64 and 70% in three dogs, respectively; 33% after pdvWF, and 92% after LMW-rvWF. The in vivo recovery of ristocetin cofactor (RCoF) was 78, 110 and 120% for rvWF, and 25% for pdvWF. Both rvWF and pdvW F caused increases in factor VIII. Although no effect was seen on bleeding time at the dosages used, the rate of blood flow from cuticle wounds was re duced after a single bolus administration of rvWF. The rvWF was able to con trol a severe nose bleed in one dog.