Flow cytometric monitoring of glycoprotein IIb/IIIa blockade and platelet function in patients with acute myocardial infarction receiving reteplase, abciximab, and ticlopidine -: Continuous platelet inhibition by the combination of abciximab and ticlopidine

Background-Improvement of thrombolysis may be achieved by concomitant strong platelet inhibition. To monitor platelet function in patients with myocardial infarction (n=46) who were treated with the fibrinolytic agent reteplase, the glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist ticlopidine, we developed a flow cytometric assay. Methods and Results-Binding of abciximab to platelets was directly monitored as the percentage of platelets stained by a goat anti-mouse antibody. flood drawn 10 minutes and 2 hours after the start of therapy with reteplase and abciximab and during the 12-hour infusion of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2 +/- 10.3%; 12 hours, 85.8 +/- 7.1%). Starting at 24 hours, abciximab binding gradually decreased (24 hours, 74.6 +/- 16.2%; 48 hours, 66.8 +/- 14.9%; 72 hours, 60.5 +/- 16.7%; 96 hours, 49.4 +/- 17.8%; 120 hours, 35.8 +/- 16.4%; and 144 hours, 29.9 +/- 15.3%). finding of a chicken anti-fibrinogen antibody to platelets, indicating the level of functional blockade of GP IIb/IIIa, was inversely correlated with the binding of abciximab (r=-0.72, P<0.0001). In blood drawn at 10 minutes, platelet aggregation was maximally inhibited but recovered within 48 hours even if the majority of GP IIb/IIIa receptors were still blocked by abciximab. Reteplase did not influence abciximab binding and did not activate platelets, as measured by P-selectin expression, fibrinogen binding, and platelet aggregation. Platelet inhibition that was achieved during the first 24 hours by abciximab was directly maintained by additional treatment with ticlopidine. Conclusions-Flow cytometric monitoring of platelet function allows differentiation of the effects of reteplase, abciximab, and ticlopidine. The combination of abciximab and ticlopidine is an attractive therapeutic strategy that provides a fast and continuous platelet inhibition.