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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
1   The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
,
Cécile M. A. Nieuwenhuys
2   Human Biology, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
,
Marion A. H. Feijge
1   The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
,
Willem Kloots
3   Unilever Health Institute, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
,
Peter L. A. Giesen
4   Synapse, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
,
Johann C. Jerling
3   Unilever 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
5   Physiology CARIM, University of Maastricht, Maastricht, The Netherlands
,
Johan W. M. Heemskerk
1   The Departments of Biochemistry, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
2   Human Biology, Unilever Research Vlaardingen, Vlaardingen, The Netherlands
› Author AffiliationsFinancial support: Support was obtained from the Netherlands Foundation for Scientific Research (902–68–241) and AstraZeneca R&D.
Further Information

Publication History

Received 12 February 2004

Accepted after resubmission 13 October 2004

Publication Date:
14 December 2017 (online)

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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
 

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