Blood, 1 September 2001, Vol. 98, No. 5, pp. 1619-1621
BRIEF REPORT
Differential inhibition of adenosine diphosphate- versus
thrombin receptor-activating peptide-stimulated platelet fibrinogen
binding by abciximab due to different glycoprotein IIb/IIIa
activation kinetics
Artur-Aron Weber and
Karsten Schrör
From the Department of Pharmacology and Clinical
Pharmacology, Heinrich-Heine University, Düsseldorf,
Germany.
The exposure of internal glycoprotein (GP) IIb/IIIa receptors has
been proposed to explain the incomplete inhibition of aggregation of
thrombin receptor-activating peptide (TRAP)-stimulated platelets by
abciximab. However, a marked and rapid externalization of GPIIb/IIIa was also observed upon stimulation with 30 µM adenosine diphosphate (ADP). ADP-induced fibrinogen binding was completely inhibited by 10 µg/mL abciximab, 30 nM tirofiban, or 3 µg/mL eptifibatide, while
fibrinogen binding induced by 100 µM TRAP was inhibited only by 50%.
Interestingly, striking differences in fibrinogen binding kinetics in
ADP- versus TRAP-stimulated platelets were observed. ADP-induced
fibrinogen binding was much slower than that of abciximab. These
differences in the fibrinogen binding rate were due to differential
GPIIb/IIIa activation kinetics because the actual fibrinogen binding
rate (measured by adding fibrinogen after platelet activation) was
similar in ADP- and TRAP-stimulated platelets. Thus, the TRAP-induced
GPIIb/IIIa activation rate would allow significant amounts of
fibrinogen to occupy externalized GPIIb/IIIa receptors even in the
presence of the inhibitor.
