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Rivista di Angiologia

Official Journal of the International Union of Angiology, the International Union of Phlebology and the Central European Vascular Forum
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,899

Periodicità: Bimestrale

ISSN 0392-9590

Online ISSN 1827-1839


International Angiology 1998 Marzo;17(1):38-42


Decrease of pla­telet intra­cel­lu­lar pH and adhe­sion by ticlop­i­dine in ­patients with vas­cu­lar dis­ease

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.

lingua: Inglese


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