Glycoprotein IIb-IIIa content and platelet aggregation in healthy volunteers and patients with acute coronary syndrome

Author： Yakushkin V.V. Zyuryaev I.T. Khaspekova S.G. Sirotkina O.V. Ruda M.YA. Mazurov A.V.

ISSN： 1369-1635

Source： Platelets, Vol.22, Iss.4, 2011-06, pp. : 243-251

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Abstract

Glycoprotein (GP) IIb-IIIa (ααIIbββ3-integrin) is the central receptor of platelet aggregation. Activated GP IIb-IIIa binds fibrinogen or von Willebrand factor, which forms molecular bridges between aggregating platelets. This review summarizes data on the relationship between GP IIb-IIIa expression on the platelet surface and platelet aggregating activity. GP IIb-IIIa number, measured as maximal binding of complex-specific monoclonal antibody, varied by approximately two fold in both healthy volunteers (n == 35) and patients with acute coronary syndrome (ACS) (n == 65). In healthy volunteers positive associations were observed between GP IIb-IIIa number and the level of ADP-induced aggregation when this relationship was analysed in untreated platelet-rich plasma (PRP) as well as upon in vitro addition of aspirin or non-saturating concentrations of GP IIb-IIIa blockers. In the same group of volunteers almost no differences in aggregating activity were detected between donors carrying the GP IIIa Pro33 allele (n == 15) and those with the GP IIIa Leu33Leu33 genotype (n == 20). No significant relationships were revealed between platelet aggregability and variations of plasma fibrinogen concentration. Positive correlation of the level of ADP-induced aggregation and GP IIb-IIIa content was detected in patients with ACS within the first hour upon admission to the hospital when they had already received aspirin, but not clopidogrel. However, there were no correlations between these parameters at days 3––5 and days 8––12 (before discharge). At these time points patients were treated not only with aspirin but were saturated with clopidogrel as well. In ACS patients we also evaluated the expression of another platelet adhesive receptor, GP Ib, and found a significant positive correlation between GP IIb-IIIa and GP Ib content. A strong association was also revealed between the number of both receptors and mean platelet volume. The latter observation indicated that individual variations of the number of glycoprotein molecules are mainly affected by platelet size but not the density of their expression on the platelet membrane. Possible usefulness of measuring GP IIb-IIIa content as a marker of increased platelet reactivity is discussed.