Differential in Vitro Effects of the Platelet Glycoprotein IIb/IIIa Inhibitors abixicimab or SR121566A on Platelet Aggregation, Fibrinogen Binding and Platelet Secretory Parameters

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• 作者：Klinkhardt ; Ute ; Kirchmaier ; Carl M. ; Westrup ; Dagmar ; Breddin ; Hans Klaus ; Mahnel ; Rene ; Graff ; Jochen ; et. al.
• 关键词：GPIIb/IIIa platelet aggregation inhibitors ; Antibodies ; Peptidomimetics ; abciximab ; SR151266A ; GP ; glycoprotein ; PTCA ; percutaneous transluminal coronary angioplasty ; MAb ; monoclonal antibody ; PRP ; platelet-rich plasma ; β ; -TG ; β ; -thromboglobulin
• 刊名：Thrombosis Research
• 出版年：2000
• 出版时间：February 15, 2000
• 年：2000
• 卷：97
• 期：4
• 页码：201-207
• 全文大小：146 K

文摘

The aim of this study was to compare fibrinogen binding, inhibition of platelet aggregation and seceretory potential of the MAb abciximab (0.5–5 μg/mL) and the peptidomimetic compound SR121- 566A (15–250 ng/mL) in vitro in whole blood. Fibrinogen binding was followed by flow cytometry; platelet function was evaluated by light transmittance and by impedance aggregometry. Secretory functions of platelets were evaluated using ATP as marker for early secretion by dense granulae and P-selectin (CD62) for α-granular secretion as well as CD63 for lysosomal degranulation. Results showed that fibrinogen binding induced by 5 μM TRAP was maximally inhibited greater than 80 % at 3 μg/mL abciximab or at 250 ng/mL SR121566A. At these concentrations of antagonists, platelet aggregation induced by 5 μM ADP or 2 μg/mL collagen was inhibited completely. Expression of CD62 was reduced 34 % with abciximab or 15 % with SR121566A; CD63 expression was reduced 22 % with both agents. With both agents, the EC₅₀ for inhibition of CD62 and CD63 expressions was in similar magnitudes than the EC₅₀ for fibrinogen binding inhibition. With 3 μg/mL abciximab, ATP secretion was maximally reduced to 50 % of the control, whereas SR121566A at 250 ng/mL had no inhibitory effect on this parameter. A slight increase in ATP secretion was seen with 0.5 μg/mL abciximab and with SR121566A in concentrations of less than 45 ng/mL. The data suggest a discoupling between the anti-aggregatory and the antisecretory effects of IIb/IIIa antagonists. Because it is not established to what extend CD62 or CD63 expression can be reduced by any means, the reduction by 20–30 % obtained by 3 μg/mL abciximab or 250 ng/mL SR121566A might already be the maximum possible inhibition by these agents.