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Official Journal of the , the International Union of Phlebology and the
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,899
Online ISSN 1827-1839
Lechi C., Gaino S., Andrioli G., Paluani F. *, Guzzo P., Bellavite P., Zatti M., Arosio E. *
From the * Institute of Medical Clinics and Chemistry and Clinic Microscopics, University of Verona, Italy
Background. Ticlopidine inhibits platelet aggregation by preventing the binding of fibrinogen to its platelet receptor. We examined whether this inhibition involved platelet transduction system such as Na+/H+ pump and platelet intracellular calcium.
Methods. Platelet adhesion in 13 patients with peripheral vascular disease treated with ticlopidine, 250 mg b.i.d for 30 days, was measured in culture microplates before and after therapy. The microplate wells were coated with human plasma, fibrinogen or collagen, and platelet adhesion was studied in the resting condition and after stimulation with 1 and 10 µM ADP. At the same time, platelet intracellular calcium and ADP-induced calcium increases were measured with the fluorescent indicator Fura 2. In addition, intracellular pH and thrombin-induced pH variations were measured with the fluorescent probe BCECF.
Results. Platelet adhesion to plasma and fibrinogen was significantly reduced (about 50%) after treatment with ticlopidine, while adhesion to collagen was not modified. Basal calcium and ADP-induced calcium increase were not significantly different before and after ticlopidine. Platelet basal intracellular pH was reduced (from 7.44±0.009 to 7.41±0.017, p<0.05), but agonist-induced alkalinisation was not significantly different. Early acidification, not dependent on Na+/H+ exchange, was also reduced (p<0.05).
Conclusions. These data do not seem to support the hypothesis that ticlopidine-induced reduction of platelet adhesion depends on alteration of the mechanisms determining signal transduction, at least as far as basal and post-stimulation intracellular calcium is concerned. On the contrary, the possibility that ticlopidine inhibits the Na+/H+ antiport remains open to consideration.