Comparison of the In Vivo Anticoagulant Properties of Standard Heparin and the Highly Selective Factor Xa Inhibitors Antistasin and Tick Anticoagulant Peptide (TAP) in a Rabbit Model of Venous Thrombosis

George P Vlasuk; Denise Ramjit; Tsuneo Fujita; Christopher T Dunwiddie; Elka M Nutt; Donna E Smith; Ronald J Shebuski

doi:10.1055/s-0038-1648131

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1991; 65(03): 257-262
DOI: 10.1055/s-0038-1648131

Original Article

Schattauer GmbH Stuttgart

Comparison of the In Vivo Anticoagulant Properties of Standard Heparin and the Highly Selective Factor Xa Inhibitors Antistasin and Tick Anticoagulant Peptide (TAP) in a Rabbit Model of Venous Thrombosis

George P Vlasuk

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Denise Ramjit

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Tsuneo Fujita

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Christopher T Dunwiddie

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Elka M Nutt

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Donna E Smith

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

,

Ronald J Shebuski

The Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, PA, USA

› Author Affiliations

Abstract

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Summary

An in vivo thromboplastin (TP)-induced venous stasis thrombosis model in rabbits was used to compare the efficacy of standard heparin with the selective factor Xa inhibitors, recombinant tick anticoagulant peptide (rTAP) and recombinant antistasin (rATS), in prophylactic prevention of thrombus formation. Heparin significantly reduced TP-induced clot formation at doses of 55 and 100 U kg⁻¹ h⁻¹ yielding clot weights of 9 ± 4 and 6 ± 2%, respectively. Clot formation was significantly decreased by i.v. infusions of rTAP at doses of 21, 37 and 64 Μg kg⁻¹ min⁻¹ resulting in normalized clot weights of 13 ± 3, 8 ± 2 and 2 ± 1%, respectively. rATS was approximately 10-fold more potent than rTAP, reducing normalized clot weights to 16 ± 5, 2 ± 1 and 1 ± 0.8% at rATS doses of 1.25, 2.5 and 5.0 Μg kg⁻¹ min⁻¹, respectively. These data suggest that factor Xa-mediated inhibition of coagulation with rTAP and rATS is as effective as conventional anticogulant treatment with heparin in preventing venous thrombosis.

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References

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