title: Axial dependence of collagen-induced thrombus formation in flowing non-anticoagulated human blood. Anti-platelet drugs impair thrombus growth and increase platelet-collagen adhesion.
abstract: Platelet thrombus formation on collagen fibrils is most pronounced at the upstream end of the surface, and it gradually decreases along the axis in parallel with the direction of the blood flow. This phenomenon, known as axial dependent platelet thrombus formation, is explained by the balance of the platelet supply to the surface and the consumption of platelets by growing thrombi. In the present study we have affected this balance by (A) inhibiting the growth of platelet thrombi by aspirin (ASA) or clopidogrel, and thus increasing the platelet concentration at the surface, and by (B) utilising blood from cigarette smokers, who have enhanced thrombus formation immediately after smoking, and thus decreasing the platelet concentration at the surface. Thrombus formation in non-anticoagulated blood was triggered by collagen fibrils positioned in a parallel-plate perfusion chamber at a wall shear rate of 2600 s-1 which is characteristic for moderately stenosed arteries. Morphometrical assessment of thrombus formation was performed at axial positions of 1 and 13 mm downstream to the blood flow inlet at the collagen surface. Platelet-collagen adhesion and thrombus volume in blood from nonsmokers were decreased at the downstream location by 39% (p < or = 0.0001) and by 60% (p < or = 0.0001), respectively. However, increasing the platelet concentration at the surface by partially inhibiting the thrombus growth by ASA or clopidogrel, reduced substantially the axial decrease in platelet adhesion and thrombus volume.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Biotechnology Centre of Oslo, Norway.
authors.forename: H E
authors.initials: HE
authors.lastname: Roald
authors.forename: K S
authors.initials: KS
authors.lastname: Sakariassen
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D000077144:Clopidogrel; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism; D018056:Hemorheology; D006801:Humans; D008297:Male; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012907:Smoking / Q000097:blood; D013314:Stress, Mechanical; D013499:Surface Properties; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin