Regulation of tissue factor-induced coagulation and platelet aggregation in flowing whole blood

Marijke J. E. Kuijpers; Cécile M. A. Nieuwenhuys; Marion A. H. Feijge; Willem Kloots; Peter L. A. Giesen; Johann C. Jerling; Mirjam G. A. oude Egbrink; Johan W. M. Heemskerk

doi:10.1160/TH04-02-0091

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(01): 97-105
DOI: 10.1160/TH04-02-0091

Platelets and Blood Cells

Schattauer GmbH

Regulation of tissue factor-induced coagulation and platelet aggregation in flowing whole blood

Marijke J. E. Kuijpers

¹The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

,

Cécile M. A. Nieuwenhuys

²Human Biology, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

,

Marion A. H. Feijge

¹The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

,

Willem Kloots

³Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

,

Peter L. A. Giesen

⁴Synapse, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

,

Johann C. Jerling

³Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

^*Present address: Potchefstroom Institute of Nutrition, School of Physiology, Nutrition and Consumer Science, Potchefstroom University for Christian Higher Education, South Africa.

,

Mirjam G. A. oude Egbrink

⁵Physiology CARIM, University of Maastricht, Maastricht, The Netherlands

,

Johan W. M. Heemskerk

¹The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

²Human Biology, Unilever Research Vlaardingen, Vlaardingen, The Netherlands

› Author Affiliations

Abstract

Summary

Photochemically induced thrombosis (a thrombin-dependent process) was measured in rats treated with moderate doses of anticoagulants, but which appeared to be unchanged. We considered the possibility that platelet-inhibiting agents, which also indirectly inhibit coagulation, would act as more potent antithrombotic agents.Inhibitors used as such were prostaglandin E₁ (PGE₁), which elevates cyclic AMP levels, and the P2Y₁₂ ADP-receptor antagonist,AR-C69931MX. Effects of these agents were investigated in an ex vivo model system, in which whole blood under coagulant conditions was perfused over fibrinogen at defined wall shear rate. Perfusion of blood (rat or human) in the presence of tissue factor resulted in deposition of activated platelets and subsequent aggregate formation, along with exposure of procoagulant phosphatidylserine (PS) on the platelet surface and formation of fibrin fibers. In the presence of PGE1 aggregation was completely inhibited,but platelet adhesion and PS exposure were only party reduced, while fibrin formation was hardly affected. Treatment with AR-C69931MX caused similar, but less complete effects.These results indicate that in tissue factor- triggered blood under conditions of flow:(i) the platelet procoagulant response is independent of aggregate formation; (ii) the platelet-inhibiting effect of PGE1 and AR-C69931MX is sufficient to suppress aggregation, but not platelet adhesion and coagulation. These platelet inhibitors thus maintain their aggregation- inhibiting effect at sites of thrombin formation.

Keywords

Coagulation - platelets - prostaglandin - thrombin - thrombus

Full Text

References

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