High Levels of Platelet Inhibition With Abciximab Despite Heightened Platelet Activation and Aggregation During Thrombolysis for Acute Myocardial Infarction

Abstract

Background-We evaluated platelet activation and aggregation in patients with acute myocardial infarction (AMI) treated with thrombolytic therapy alone or with reduced-dose thrombolysis and concomitant abciximab. Methods and Results-The study was performed in 20 control subjects and 51 patients with AMI before and after reperfusion with either alteplase or reteplase or reduced doses of these agents with concomitant abciximab. Platelet activation was assayed by platelet surface expression of P-selectin. Turbidometric platelet aggregation in response to ADP was measured in patients before thrombolytic therapy and 90 minutes and 24 hours after the beginning of thrombolytic therapy. P-selectin expression was greater at baseline in patients than normal control subjects (30.4% versus 9.8%, PϽ0.0001) but was identical between the 2 groups after stimulation with ADP (64.4% versus 69.3%, Pϭ0.37). However, at 24 hours, basal P-selectin expression declined in patients (Pϭ0.0025 versus baseline), whereas ADP-stimulated P-selectin expression was lower in patients than in control subjects (48% versus 69%, Pϭ0.0004).When combined with reduced doses of either alteplase or reteplase, abciximab achieved 91% and 83% inhibition of 5 and 20 mol/L ADP-induced platelet aggregation, which decreased to 46% and 40%, respectively, at 24 hours. No appreciable difference in the platelet inhibition profile of abciximab was observed between the 2 thrombolytics. Conclusions-Platelet activation and aggregation are heightened in the setting of thrombolysis for AMI. Despite this enhanced level of platelet activation, abciximab, combined with a reduced-dose thrombolytic, inhibited platelet aggregation similarly to the level reported in elective settings.

Circulating Monocyte-Platelet Aggregates Are a More Sensitive Marker of In Vivo Platelet Activation Than Platelet Surface P-Selectin

“…2,3,5,6 In this study, however, we demonstrate by 3 independent methods (in vivo tracking of activated platelets in baboons, human PCI, and human AMI) that circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin.…”

“…4 Platelet surface P-selectin is considered to be the "gold standard" marker of platelet activation. 2,3,5,6 In vitro, the activationdependent increase in platelet surface P-selectin is not reversible over time. 7 We 8 and others, 9 however, have recently demonstrated that in vivo circulating degranulated platelets rapidly lose their surface P-selectin yet continue to circulate and function.…”

The Efficacy and Safety of Pharmacoinvasive Therapy with Prourokinase for Acute ST‐Segment Elevation Myocardial Infarction Patients with Expected Long Percutaneous Coronary Intervention‐Related Delay

“…First, 300-600 mg upfront loading dose of clopidogrel was used in all patients prior to PCI procedures to decrease ischemic complications. It was reported that fibrinolysis by t-PA is followed by increased platelet activation and aggregation, and that the stent implantation early after fibrinolysis at the circumstance of inadequate antiplatelet therapy may be associated with an increased rate of acute stent thrombosis [5,16]. The optimized antiplatelet conjunction therapy in this study could in part explain the better clinical outcomes.…”

Platelet Function and Fibrinolytic Agents: Two Sides of a Coin?

“…The data from in vivo studies also suggest that t-PA induces platelet aggregation [27, 28]and that this process can be prevented effectively by IIb/IIIa inhibitors [29, 30]. The alteplase-abciximab combination seems very promising and improved 90-min thrombolysis in myocardial infarction (TIMI) 3 flow from 57 to 76% in the TIMI 14 trial [30].…”