Clopidogrel--a platelet inhibitor which inhibits thrombogenesis in non-anticoagulated human blood independently of the blood flow conditions.
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 beta-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 microscopy 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Roald
H E
HE
Biotechnology Centre of Oslo, University of Oslo, Norway.
Barstad
R M
RM
Kierulf
P
P
Skjørten
F
F
Dickinson
J P
JP
Kieffer
G
G
Sakariassen
K S
KS
D000328:Adult; D000925:Anticoagulants; D001783:Blood Flow Velocity; D000077144:Clopidogrel; D005337:Fibrin / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D006403:Hematologic Tests; D006801:Humans; D008297:Male; D015539:Platelet Activation; D010973:Platelet Adhesiveness / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010976:Platelet Count / Q000187:drug effects; D013927:Thrombosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D005344:Fibrinopeptide A; D005337:Fibrin; D000077144:Clopidogrel; D013988:Ticlopidine