Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation

Citation
S. Goto et al., Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation, PLATELETS, 12(7), 2001, pp. 406-414
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
PLATELETS
ISSN journal
0953-7104 → ACNP
Volume
12
Issue
7
Year of publication
2001
Pages
406 - 414
Database
ISI
SICI code
0953-7104(200111)12:7<406:EOTOVW>2.0.ZU;2-N
Abstract
Ticlopidine, recently classified as a P2Y(12) ADP receptor blockade, is kno wn to be an effective antiplatelet agent preventing arterial thrombosis, e. g., myocardial infarction or cerebral infarction, but the mechanism of the in vivo antithrombotic effects of ticlopidine is not fully understood. Bloo d was drawn from seven normal volunteers before and 7 days after consecutiv e intake of ticlopidine, and 1 day after oral intake of aspirin after 7 day s of ticlopidine wash-out period. Effects of drug intake on shear-induced v on Willebrand factor (vWF) binding to platelets, platelet activation eviden ced by P-selectin surface expression and translocation of GP Iba, and vWF-m ediated platelet aggregation, were investigated by using an optically modif ied cone-plate viscometer and quantitative flow cytometry. The maximum exte nt of platelet aggregation occurring under a high shear rate of 10800 s(-1) , presumably mediated by vWF, was not significantly influenced by either ti clopidine or aspirin. However, significant dissociation of once aggregated platelets occurred in samples obtained after ticlopidine intake (25.4 +/-9. 3%, P=0.00030) and less significantly after aspirin intake (15.9 +/-5.7%, P =0.0013), while only insignificant and modest dissociation occurred in cont rols (6.3 +/-4.4%, n.s.). Binding experiments also revealed that the shear- induced vWF binding to platelets was significantly inhibited by ticlopidine , and less significantly by aspirin, although other indicators of platelet activation, such as shear-induced P-selectin expression and GP Ib alpha tra nslocation were not influenced by either ticlopidine or aspirin. We demonst rate here that platelet aggregation mediated by von Willebrand factor (vWF) under a high shear rate of 10800 s(-1) cannot be stabilized and that disso ciation occurs readily when ADP receptor stimulation is blocked by continuo us intake of ticlopidine, indicating that these effects on platelet thrombu s formation may contribute to the in vivo antithrombotic effects of ticlopi dine.