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The Effect of Tirofiban on Fibrinogen/Agonist-Induced Platelet Shape Change and Aggregation

Departments of Clinical Biochemistry and Surgery, Royal Free University College School of Medicine, University College London, University of London, Royal Free Hospital Campus, London, UK

Dimitri P. Mikhailidis, MD, FRCP, FRCPath

Departments of Clinical Biochemistry and Surgery, Royal Free University College School of Medicine, University College London, University of London, Royal Free Hospital Campus, London, UK, mikhailidis@ aol.com

There is evidence linking raised plasma fibrinogen (fib) and platelet hyperactivity with vascular events. One way to inhibit platelets is to block the platelet membrane glycoprotein (GP) IIb/IIIa receptor, which binds circulating fib or von Willebrand factor and cross-links platelets at the final common pathway to platelet aggregation. Tirofiban is a potent and specific fib receptor antagonist, used in the treatment of unstable angina. The authors assessed the effect of tirofiban on spontaneous platelet aggregation (SPA), fib-induced, serotonin (5HT)-induced, and adenosine diphosphate (ADP)-induced aggregation in whole blood by calculating the percentage free platelet count. These various agonists were used alone and in combination. The authors also measured the effect of tirofiban on agonists-induced (ADP, 5HT) platelet shape change (PSC). The effect of fib on PSC was also evaluated in platelet-rich plasma using a high-resolution (0.07 fL) channelyzer. Tirofiban significantly inhibited SPA, fib (2, 4, 8 g/L), ADP, ADP + fib combination, and 5HT-induced aggregation. Tirofiban had no effect on agonist-induced PSC. There was no apparent change in platelet volume with fib. In conclusion, tirofiban does not appear to have an effect on PSC, an early phase of platelet activation. Tirofiban seems to be a nonspecific and an effective inhibitor of platelet aggregation (a later phase of platelet activation) in whole blood. The clinical significance of these findings remains to be established.

Key Words: fibrinogen • platelet aggregation • platelet shape change • platelet volume • tirofiban • glycoprotein IIb/IIIa

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