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Sandra M. Penz, Armin J. Reininger, Orsolya Toth, Hans Deckmyn, Richard Brandl, Wolfgang Siess
Glycoprotein Ib inhibition and ADP receptor antagonists, but not aspirin, reduce platelet thrombus formation in flowing blood exposed to atherosclerotic plaques
Keywords: ADP receptor antagonists, Aspirin, GPIb, plaque, platelet thrombus formation
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) Ib 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-C69931MX, but not by GPIb blockade with the mAB 6B4. Inhibition of platelet aggregation by MRS2179 was 74 37% and 68 20%, by AR-C69931MX 94 7% and 80 6%, and by aspirin 88 19% and 64 28%, in PRP and blood, respectively (mean SD; n = 612 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 (1,500s1), blockade of platelet GPIb resulted in a strong decrease of plaque-stimulated platelet adhesion/aggregate formation of 77 5% (mean SD; n = 4). Furthermore, MRS2179, AR-C69931MX 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 GPIb-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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 97, 03/2007
Pages: 435 - 443