Ticlopidine Selectively Inhibits Human Platelet Responses to Adenosine Diphosphate

Marco Cattaneo; Benjaporn Akkawat; Anna Lecchi; Claudio Cimminiello; Anna M Capitanio; Pier Mannuccio Mannucci

doi:10.1055/s-0038-1646487

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1991; 66(06): 694-699
DOI: 10.1055/s-0038-1646487

Original Article

Schattauer GmbH Stuttgart

Ticlopidine Selectively Inhibits Human Platelet Responses to Adenosine Diphosphate

Marco Cattaneo

The A. Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, I.R.C.C.S. Maggiore Hospital and University of Milan, Milan, Italy

,

Benjaporn Akkawat

The A. Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, I.R.C.C.S. Maggiore Hospital and University of Milan, Milan, Italy

,

Anna Lecchi

The A. Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, I.R.C.C.S. Maggiore Hospital and University of Milan, Milan, Italy

,

Claudio Cimminiello

^*The Medicina IV, San Carlo Hospital, Milan, Italy

,

Anna M Capitanio

The A. Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, I.R.C.C.S. Maggiore Hospital and University of Milan, Milan, Italy

,

Pier Mannuccio Mannucci

The A. Bianchi Bonomi Hemophilia and Thrombosis Center, Institute of Internal Medicine, I.R.C.C.S. Maggiore Hospital and University of Milan, Milan, Italy

› Author Affiliations

Abstract

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Summary

Platelet aggregation and fibrinogen binding were studied in 15 individuals before and 7 days after the oral administration of ticlopidine (250 mg b.i.d.). Ticlopidine significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), the endoperoxide analogue U46619, collagen or low concentrations of thrombin, but did not inhibit platelet aggregation induced by epinephrine or high concentrations of thrombin. Ticlopidine inhibited ¹²⁵I-fibrinogen binding induced by ADP, U46619 or thrombin (1 U/ml). The ADP scavengers apyrase or CP/CPK, added in vitro to platelet suspensions obtained before ticlopidine, caused the same pattern of aggregation and ¹²⁵I-fibrihogen binding inhibition as did ticlopidine. Ticlopidine did not inhibit further platelet aggregation and ¹²⁵I-fibrinogen binding induced in the presence of ADP scavengers. After ticlopidine administration, thrombin or U46619, but not ADP, increased the binding rate of the anti-GPIIb/IIIa monoclonal antibody 7E3 to platelets. Ticlopidine inhibited clot retraction induced by reptilase plus ADP, but not that induced by thrombin or by reptilase plus epinephrine, and prevented the inhibitory effect of ADP, but not that of epinephrine, on the PGE₁-induced increase in platelet cyclic AMP. The number of high- and low-affinity binding sites for ³H-ADP on formalin-fixed platelets and their K _d were not modified by ticlopidine. These findings indicate that ticlopidine selectively inhibits platelet responses to ADP.

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References

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