EFFECTS OF HUMAN RECOMBINANT, PLASMA-DERIVED AND PORCINE VON-WILLEBRAND-FACTOR IN PIGS WITH SEVERE VON-WILLEBRAND DISEASE

The effects of the infusion of a human recombinant von Willebrand fact or (VWF) preparation in pigs homozygous for von Willebrand disease (vW D) were evaluated on serial measurements of von Willebrand factor anti gen and activity, FVIII activity, VWF multimer analysis, in-vivo bleed ing time and platelet adhesion and thrombus formation on collagen at h igh shear rates in an ex-vivo model of experimental thrombosis. Plasma -derived human and porcine vWF were used for comparison. Before infusi on, the pigs were characterized by undetectable plasma VWF levels, a l ow level of VIII, prolonged bleeding time, severely impaired platelet adhesion and thrombus formation. After infusion of the human recombina nt vWF, in-vivo recovery of vWF activity ranged from 58% to 82%, depen ding on the dose infused, and its half-life was longer than for the pl asma-derived concentrates. The highest-molecular-weight forms of human recombinant vWF were removed from the circulation gradually. Infusion of the three vWF concentrates produced inconsistent effects on bleedi ng time and moderate improvement of platelet adhesion and thrombus for mation. After infusion, a prolonged increase of FVIII (> 48 h) was obs erved, suggesting that human recombinant vWF is able to bind and to st abilize porcine factor VIII and that porcine vWD is a good model for s tudying such interactions. Blood Coag Fibrinol 9:361-372 (C) 1998 Lipp incott-Raven Publishers.