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Thromb Haemost 2007; 97(03): 435-443
DOI: 10.1160/TH06-07-0415
Platelets and Blood Cells
Schattauer GmbH

Glycoprotein Ibα inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques

Sandra M. Penz
1   Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany
,
Armin J. Reininger
2   Department of Transfusion Medicine and Hemostaseology, University of Munich, Munich, Germany
,
Orsolya Toth
1   Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany
3   1stDepartment of Medicine, University of Pécs, Pécs, Hungary
,
Hans Deckmyn
4   Laboratory for Thrombosis Research, IRC, KU Leuven Campus Kortrijk, Kortrijk, Belgium
,
Richard Brandi
5   Department of Vascular Surgery, Klinikum Munich-Schwabing, Munich, Germany
,
Wolfgang Siess
1   Institute for Prevention of Cardiovascular Diseases, University of Munich, Munich, Germany
› Author AffiliationsFinancial support: The study was supported by the grants from the Deutsche Forschungsgemeinschaft (Graduate Program GK 438 „Vascular Biology in Medicine”; Si-274/9) (S.M.P.; W.S.), the Friedrich-Baur foundation and the August-Lenz foundation (O.T).
Further Information

Publication History

Received 29 July 2006

Accepted after resubmission 29 February 2006

Publication Date:
28 November 2017 (online)

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Summary

Anti-platelet drugs are used to prevent intra-arterial thrombus formation after rupture of atherosclerotic plaques. Until now, the inhibitory effect of present and future anti-platelet drugs such as aspirin, ADP receptor P2Y1/P2Y12 antagonists and glycoprotein (GP) Ibα inhibitors on the interaction of platelets with human plaques is not known. To study those effects we obtained human atherosclerotic plaques by surgical endarterectomy. Plaques induced maximal platelet aggregation in hirudinized platelet-rich plasma (PRP) and blood that was effectively inhibited by aspirin, the P2Y1 antagonist MRS2179 and the P2Y12 antagonist AR-C69931 MX, but not by GPIbα blockade with the mAB 6B4. Inhibition of platelet aggregation by MRS2179 was 74 ± 37% and 68 ± 20%, by AR-C69931 MX 94 ± 7% and 80 ± 6%, and by aspirin 88 ± 19% and 64 ± 28%, in PRP and blood, respectively (mean ± SD; n6–12 with plaques from 6 patients). The combination of both ADP receptor antagonists completely inhibited plaque-induced platelet aggregation in hirudinized PRP and blood. Under arterial flow conditions (1,500s-1), blockade of platelet GPIbα– resulted in a strong decrease of plaque-stimulated platelet adhesion/aggregate formation of 77 ± 5% (mean ± SD; n=4). Furthermore, MRS2I79, AR-C6993IMX and their combination reduced plaque-dependent platelet aggregate formation by 35 ± 14%, 32 ± 13% and 58 ± 12% (mean ± SD; n=5), respectively. Aspirin was without significant effect. In conclusion, a GPIbα-blocking antibody, as well as P2Y1 and P2Y12 receptor antagonists, alone or in combination, reduce in contrast to aspirin human plaque-induced platelet thrombus formation under arterial flow. Although these new anti-platelet agents inhibit platelet thrombus formation after plaque rupture, more efficient platelet blockers are required.

Keywords

ADP receptor antagonists - aspirin - GPIb - plaque - platelet throm bus formation
 

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