Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation

The Journal of Clinical Investigation
P GreseleM Colucci

Abstract

Activated protein C (APC) is a potent physiologic anticoagulant with profibrinolytic properties, and has been shown to prevent thrombosis in different experimental models. We investigated the effect of human APC on thrombin-induced thromboembolism in mice, a model of acute intravascular fibrin deposition leading to death within minutes. APC given intravenously (i.v.) as a bolus 2 min before thrombin challenge (1,250 U/kg) reduced mortality in a dose-dependent manner despite the lack of thrombin inhibitor activity. Significant inhibition of thrombin-induced death was observed at the dose of 0.05 mg/kg, and maximal protection was obtained with 2 mg/kg (> 85% reduction in mortality rate). Histology of lung tissue revealed that APC treatment (2 mg/kg) reduced significantly vascular occlusion rate (from 89.2 to 46.6%, P < 0.01). The protective effect of APC was due to the inhibition of endogenous thrombin formation as indicated by the fact that (a) the injection of human thrombin caused a marked decrease in the coagulation factors of the intrinsic and common pathways (but not of Factor VII), suggesting the activation of blood clotting via the contact system; (b) APC pretreatment reduced markedly prothrombin consumption; (c) the leth...Continue Reading

References

Feb 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·C T Esmon
Oct 1, 1992·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·S I Rapaport, L V Rao
Sep 2, 1991·Science·D Gailani, G J Broze
Apr 1, 1990·American Journal of Hematology·K OkajimaN Aoki
Mar 1, 1987·The Journal of Clinical Investigation·F B TaylorK E Blick
Feb 15, 1987·Thrombosis Research·M D Burdick, R G Schaub
Feb 1, 1980·The Journal of Clinical Investigation·Y Sakata, N Aoki
Jul 1, 1984·The Journal of Clinical Investigation·M ColucciD Collen
Nov 1, 1981·The Journal of Clinical Investigation·P C Comp, C T Esmon
Jan 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·B J Warn-Cramer, S I Rapaport
May 30, 1997·The Journal of Biological Chemistry·D V SakharovD C Rijken

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Citations

Mar 26, 2004·Thrombosis Research·Ryota OhashiNaohiro Kanayama
Jun 14, 2000·European Journal of Pharmacology·S MomiP Gresele
Oct 8, 2003·Transplantation Proceedings·J MalyszkoM Mysliwiec
Jan 24, 2002·Trends in Pharmacological Sciences·Paolo Gresele, Giancarlo Agnelli
Jul 19, 2002·Seminars in Hematology·John H GriffinJosé A Fernández
Oct 8, 2011·Thrombosis and Haemostasis·Jolanta M Siller-MatulaBernd Jilma
Jan 10, 2002·The Journal of Clinical Investigation·Mariko NagashimaJohn Morser
Nov 6, 2002·The Journal of Clinical Investigation·Carmen M SwaisgoodEdward F Plow
Jul 12, 2008·The Journal of Clinical Investigation·Joshua H WongEthan J Weiss
Aug 11, 2006·World Journal of Emergency Surgery : WJES·Bernard J Benedetto, Michael A Houston
Sep 20, 2005·Critical Care : the Official Journal of the Critical Care Forum·William L MaciasJean-Michel S Planquois
Jan 1, 2008·The Libyan Journal of Medicine·Bredan As, Cauwels A
Jun 16, 2006·Expert Opinion on Drug Safety·David Royston, Asha Chhatwani
Dec 27, 2005·Best Practice & Research. Clinical Haematology·Marcel LeviTom van der Poll
May 30, 2009·The FEBS Journal·Tomotaka HaradaKeiji Hasumi
Sep 29, 2015·Journal of Materials Science. Materials in Medicine·Dominika LukovicMariann Gyöngyösi
Sep 30, 2006·Annals of Medicine·Bonno N Bouma, Laurent O Mosnier
Apr 18, 2015·International Journal of Biological Macromolecules·Luciana Serrão WermelingerRussolina Benedeta Zingali
Mar 5, 2005·Journal of Cardiothoracic and Vascular Anesthesia·Rosaleen ChunDavid Royston
May 29, 2007·European Journal of Medicinal Chemistry·Lídia M LimaEliezer J Barreiro
Oct 26, 2005·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·O KaftanS Dagdas
Apr 9, 2001·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·K SchattemanD Hendriks
May 25, 2004·Anesthesia and Analgesia·Brian S Donahue
Jun 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mario ColucciPaolo Gresele
Dec 16, 2000·Arteriosclerosis, Thrombosis, and Vascular Biology·L Bajzar

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