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Von Willebrand syndrome induced by a Bothrops venom factor: bioassay for venom coagglutinin.

  • K M Brinkhous
  • D S Barnes
  • J Y Potter
  • M S Read
Publication Date
May 01, 1981
  • Biology
  • Medicine


Hereditary deficiency of the macromolecular Factor VIII complex results in classic von Willebrand disease in man and animals, a bleeder state characterized by loss of the multiple biologic activities associated with the Factor VIII complex, including the platelet-aggregating von Willebrand factor. The bleeding time is also long. Venom coagglutinin, a Bothrops factor that causes platelet aggregation in vitro, depletes the plasma of its von Willebrand factor. The rate of platelet aggregation is a function of the amount of the coagglutinin present. Based on this observation, a sensitive and quantitative assay for the venom coagglutinin was developed. We administered the purified Bothrops factor to normal pigs and dogs and induced a von Willebrand syndrome similar to the inherited disease. The plasma von Willebrand factor was severely depleted; the antihemophilic factor and the Factor VIII-related antigen were not depleted as much. The bleeding time was normal. During the induction phase of the syndrome, transient thrombocytopenia with a long bleeding time occurred. The pig was less sensitive than the dog to the effect of coagglutinin. The severity of the syndrome is determined by the amount of venom coagglutinin administered. It is suggested that the syndrome could be induced in any mammalian species because the plasma of all mammals tested in vitro is sensitive to the venom factor. This model provides another avenue for the study of the heterogeneity of the Factor VIII complex and the pathophysiology of its components.

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