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Thromb Haemost 1994; 71(05): 655-662
DOI: 10.1055/s-0038-1642499
Review Article
Schattauer GmbH Stuttgart

Clopidogrel – a Platelet Inhibitor which Inhibits Thrombogenesis in Non-Anticoagulated Human Blood Independently of the Blood Flow Conditions

Helge E Roald
1   The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
,
R Marius Barstad
1   The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
,
Peter Kierulf
2   The Clinical Chemistry Department, Ullevaal University Hospital, Oslo, Norway
,
Fredrik Skjørten
3   The Department of Pathology, Ullevaal University Hospital, Oslo, Norway
,
John P Dickinson
4   The Sanofi Winthrop Ltd., Manchester, UK
,
Gilles Kieffer
5   The Sanofi Recherche, Montpellier, France
,
Kjell S Sakariassen
1   The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway
› Author Affiliations
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Publication History

Received 05 October 1993

Accepted after revision 19 January 1993

Publication Date:
06 July 2018 (online)

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Summary

The goal of the present study was to investigate the effect of 7 and 14 days of daily oral administration of 75 mg clopidogrel on collagen-induced thrombogenesis in flowing non-anticoagulated human blood. Blood was drawn directly from an antecubital vein over immobilised collagen type III fibrils positioned in a parallel-plate perfusion chamber. The wall shear rates at the collagen surface were those characteristic for veins (100 s−1), and for medium sized (650 s−1) and moderately stenosed (2600 s−1) arteries.

Clopidogrel ingestion reduced the thrombus volume significantly (p <0.05) at 100 and 2600 s−1 (39 and 51% respectively). The β-thromboglobulin plasma levels were reduced concomitantly. However, it was not possible to measure accurately the thrombus volume at 650 s−1, due to loose packing of the platelet thrombi. Transmission electron micros-copy substantiated this observation and showed that clopidogrel profoundly reduced the platelet degranulation process (p <0.005). The inhibitory effect of clopidogrel on platelet consumption by the growing thrombi resulted apparently in higher platelet concentration at the collagen surface, which enhanced the platelet-collagen adhesion at all three shear rates (p <0.05). Despite the low deposition of fibrin on collagen, clopidogrel reduced significantly the fibrinopeptide A plasma levels and the fibrin deposition at shear rates below 650 s−1. This was apparently a consequence of the reduced platelet recruitment and the lower activation of platelets, since activated platelets in thrombi promote deposition of fibrin.

Thus, it appears that clopidogrel inhibits thrombus formation in human blood primarily by interfering with platelet-platelet binding and the inhibition is effective independently of the wall shear rate.

 

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