Effects of human recombinant, plasma-derived and porcine von Willebrand factor in pigs with severe von Willebrand disease

Blood Coagul Fibrinolysis. 1998 Jun;9(4):361-72. doi: 10.1097/00001721-199806000-00009.

Abstract

The effects of the infusion of a human recombinant von Willebrand factor (vWF) preparation in pigs homozygous for von Willebrand disease (vWD) were evaluated on serial measurements of von Willebrand factor antigen and activity, FVIII activity, vWF multimer analysis, in-vivo bleeding time and platelet adhesion and thrombus formation on collagen at high shear rates in an ex-vivo model of experimental thrombosis. Plasma-derived human and porcine vWF were used for comparison. Before infusion, the pigs were characterized by undetectable plasma vWF levels, a low level of FVIII, prolonged bleeding time, severely impaired platelet adhesion and thrombus formation. After infusion of the human recombinant vWF, in-vivo recovery of vWF activity ranged from 58% to 82%, depending on the dose infused, and its half-life was longer than for the plasma-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 bleeding time and moderate improvement of platelet adhesion and thrombus formation. After infusion, a prolonged increase of FVIII (> 48 h) was observed, suggesting that human recombinant vWF is able to bind and to stabilize porcine factor VIII and that porcine vWD is a good model for studying such interactions.

MeSH terms

  • Animals
  • Bleeding Time
  • Blood Cell Count
  • Blood Platelets / cytology
  • Cell Adhesion
  • Collagen / metabolism
  • Factor VIII / analysis
  • Glass
  • Half-Life
  • Homozygote
  • Humans
  • Perfusion / methods
  • Recombinant Proteins / analysis
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Stress, Mechanical
  • Swine
  • Thrombosis / etiology
  • Thrombosis / metabolism
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / genetics
  • von Willebrand Diseases / therapy*
  • von Willebrand Factor / analysis
  • von Willebrand Factor / pharmacology
  • von Willebrand Factor / therapeutic use*

Substances

  • Recombinant Proteins
  • von Willebrand Factor
  • Factor VIII
  • Collagen