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.
