Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation

R. D. McBane, W. E. Wysokinski, J. H. Chesebro, W. G. Owen

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21 Scopus citations

Abstract

Endogenously activated protein C is evaluated for antithrombotic activity in porcine carotid arteries subjected to mechanical trauma. Protein C is activated by intravenous administration of guanidinobenzoyl-thrombin, which binds to thrombomodulin and there deacylates to yield thrombin. The bound, transiently active thrombin yields a peak of anticoagulant activity between 5 and 10 min after infusion of the latent thrombin. Inhibition of thrombin binding in vivo by co-infusing an active-site-blocked thrombin preparation elicits acute and lethal systemic thrombosis. Nearly occlusive platelet thrombosis, which occurs within 30 min of crushing 1 cm segments of carotid arteries with a standard hemostat, is blocked by endogenous protein C activation initiated 2 min before the crush injury. It is concluded that activated protein C blocks thrombosis in deeply injured musculo-elastic arteries, and that activation of latent thrombin bound to thrombomodulin in vivo is a practical means for delivery of pharmacologically effective concentrations of activated protein C.

Original languageEnglish (US)
Pages (from-to)879-885
Number of pages7
JournalThrombosis and Haemostasis
Volume74
Issue number3
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Hematology

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    McBane, R. D., Wysokinski, W. E., Chesebro, J. H., & Owen, W. G. (1995). Antithrombotic action of endogenous porcine protein C activated with a latent porcine thrombin preparation. Thrombosis and Haemostasis, 74(3), 879-885.