Summary

Background: The ability of abciximab to prevent fibrinogen bindingto activated platelets indicates it may also promote dissolution ofplatelet-rich thrombi. The present study examined the capacity of abci-ximabto reverse platelet aggregation in vitro. Methods and Results:Experiments were performed on blood from healthy non-medicateddonors. Platelet aggregate formation and disaggregation were monito-redturbidimetrically. Platelet-bound fibrinogen was measured by flowcytometry. For disaggregation studies, platelets were first stimulatedwith either ADP or the 11-mer thrombin receptor activating peptide(TRAP), then varying amounts of abciximab were added at periodicintervals after agonist addition. Platelet disaggregation was detected bycomparing the extent of light transmittance at 4 min after addition ofeither abciximab or saline to PRP. ATP release was simultaneouslymonitored by chemi-luminescence. When added 1 min after lowconcentrations of ADP, abciximab rapidly (<1 min) dispersedplatelet aggregates in a dose-dependent manner, with complete disag-gregationobserved with 6.25 g/mL of the 3 antagonist. In contrast,equivalent concentrations of abciximab did not induce appreciabledisaggregation to platelets stimulated with TRAP (10 M). Plateletcounts of samples that had undergone complete disaggregation, asassessed by aggregometry, were equivalent to baseline, indicatingdispersal of aggregates to single cells. Concentrations of abciximab thatproduced complete disaggregation induced partial displacement ofplatelet-bound fibrinogen (52 ± 8% inhibition of fibrinogen binding at12.5 g/ml abciximab). The disaggregation effectiveness of abciximabdecreased as the time between ADP and subsequent abciximab addi-tionwidened, and as the amount of both dense granule release andagonist stimulation increased. However, pre-treatment of plateletswith acetylsalicylic acid (ASA) did not potentiate platelet disaggrega-tioninduced by abciximab. Conclusions: These data indicate thatabciximab facilitates the dispersal of newly formed platelet aggregatesin vitro, by partially displacing fibrinogen from activated GPIIb/IIIareceptors. In vivo, abciximab may destabilize coronary thrombi bypreventing aggregate formation and dispersing mural thrombi.