Schwarz H P, Dorner F, Mitterer A, Mundt W, Schlokat U, Pichler L, Turecek P L
Hyland Immuno Division, Baxter Healthcare, Vienna, Austria.
Haemophilia. 1998;4 Suppl 3:53-62. doi: 10.1046/j.1365-2516.1998.0040s3053.x.
Dutch Kooiker dogs with hereditary von Willebrand disease have undetectable levels of von Willebrand factor (vWF), resulting in spontaneous haemorrhage of mucosal surfaces similar to the clinical picture of von Willebrand disease in humans. We used this canine model of von Willebrand disease to study the in vivo effects of a new recombinant von Willebrand factor (rvWF) preparation that contained 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). Administration of rvWF in these vWF-deficient dogs resulted in a vWF:Ag half-life of 21.6 h in one dog and 22.1 h in a second dog. Administration of pdvWF resulted in a half-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, 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 pdvWF caused increases in FVIII. Although no effect was seen 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 was able to control a severe nose bleed in one dog.
患有遗传性血管性血友病的荷兰库伊克犬体内血管性血友病因子（vWF）水平检测不到，导致黏膜表面自发性出血，临床表现与人类血管性血友病相似。我们利用这种犬类血管性血友病模型，研究一种新型重组血管性血友病因子（rvWF）制剂的体内效应，该制剂包含所有种类的vWF多聚体，并与仅含低分子量多聚体的rvWF组分（LMW - rvWF）以及血浆源性因子VIII/vWF浓缩物（pdvWF）进行比较。给这些vWF缺乏的犬类注射rvWF后，一只犬的vWF:Ag半衰期为21.6小时，另一只犬为22.1小时。注射pdvWF后，vWF:Ag半衰期为7.7小时，注射LMW - rvWF后为9小时。三只犬注射rvWF后，vWF:Ag的体内回收率分别为59%、64%和70%；注射pdvWF后为33%，注射LMW - rvWF后为92%。rvWF ristocetin辅因子（RCoF）的体内回收率为78%、110%和120%，pdvWF为25%。rvWF和pdvWF均导致FVIII增加。尽管在所使用的剂量下未观察到对出血时间有影响，但单次推注rvWF后，角质层伤口的血流速度降低。rvWF能够控制一只犬的严重鼻出血。
