Search PubMed⌕ Search

PubMed · 11257073

Testing platelet activation with a shear-dependent platelet function test versus aggregation-based tests: relevance for monitoring long-term glycoprotein IIb/IIIa inhibition.

Abstract

BACKGROUND: Tests developed to monitor glycoprotein (GP) IIb/IIIa blockade do not properly reflect platelet function in vivo and need a baseline (pretreatment) value. Because GP IIb/IIIa is essential in platelet aggregation and thrombosis under shear conditions, a flow-dependent approach to monitor its inhibition can be used. METHODS AND RESULTS: We compared a test based on flow-dependent platelet deposition, the Cone and Platelet Analyzer (CPA), with in vitro platelet aggregometry and the Rapid Platelet Function Assay (RPFA) on platelet function after GP IIb/IIIa inhibition. In vitro, increasing concentrations of abciximab (0% to 100% receptor occupancy) were tested. Ex vivo, platelet function was monitored with the CPA and with aggregometry for up to 1 week after abciximab administration. The CPA was better correlated with the percentage of free GP IIb/IIIa receptors than was aggregometry or the RPFA. Only the RPFA, when expressed as a ratio over baseline (pretreatment), was comparable to the CPA. Ex vivo, the CPA, but not aggregometry, showed prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade in the first week after abciximab administration. CONCLUSIONS: Platelet function assessment by shear-induced deposition is a reliable test to monitor a wide range of GP IIb/IIIa inhibition. Its accuracy does not require a baseline reference. The effects of GP IIb/IIIa blockade on platelet function should be examined under high shear conditions.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J I Osende, V Fuster, E I Lev, D Shimbo, U Rauch, J D Marmur, M Richard, D Varon, J J Badimon. 2001-03-20. Testing platelet activation with a shear-dependent platelet function test versus aggregation-based tests: relevance for monitoring long-term glycoprotein IIb/IIIa inhibition.. https://doi.org/10.1161/01.cir.103.11.1488

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Ventricular septal rupture following abciximab infusion.

Ventricular septal rupture is a rare complication of myocardial infarction. Despite a significant reduction in its incidence with reperfusion therapy, thrombolysis has been implicated in the pathogenesis of septal rupture. There is little information regarding the impact of glycoprotein IIb-IIIa receptor blockers on ventricular septal rupture. We report a case of rupture of the ventricular septum occurring after treatment with the glycoprotein IIb-IIIa receptor blocker abciximab, in the absence of thrombolysis.

Abciximab↗

Thrombus predicts ischemic complications during percutaneous coronary intervention in saphenous vein grafts: results from TARGET (do Tirofiban and ReoPro give similar efficacy trial?).

BACKGROUND: Saphenous vein graft (SVG) percutaneous coronary intervention (PCI) carries a high risk of ischemic complications. However, there are scant recent data to identify which SVG lesions carry particularly high risk in recent years. We studied demographic and angiographic factors associated with ischemic complications after SVG PCI without distal protection in the TARGET (do tirofiban and reopro give similar efficacy trial?) study. METHODS: TARGET was a multicenter double-dummy, double-blinded study randomizing 4,809 PCI patients to tirofiban or abciximab. Of these, 254 patients underwent PCI involving an SVG lesion. The primary endpoint of this analysis was major adverse cardiac events (MACEs) at 30 days, including death, nonfatal myocardial infarction (MI), and urgent target vessel revascularization. RESULTS: No demographic characteristic was associated with 30-day MACE. Lesion length > 20 mm (odds ratio [OR] = 2.7, P = 0.03), thrombus (OR = 3.9, P = 0.003), eccentricity (P = 0.001), thrombolysis in myocardial infarction flow < 3 post-procedure (OR = 5.6, P = 0.037), and >1 target lesion (OR = 2.5, P = 0.035) were univariate variables associated with 30-day MACE. Multivariate analysis associated only thrombus (OR = 3.8, P = 0.015) with 30-day MACE. No difference in outcomes was noted between patients receiving abciximab and tirofiban. SVG patients had lesser angiographic success (95.6% vs. 98%, P = 0.04) and increased 30-day Q-wave MI (2.5% vs. 0.9%, P = 0.039) compared with non-SVG patients, but a similar incidence of death (0% vs. 0.4%), non-Q-MI (5.9% vs. 4.5%), and target vessel revascularization (0.5% vs. 1%). CONCLUSION: In the era of routine stenting and GpIIb/IIIa inhibitors, thrombus is the angiographic characteristic most closely associated with adverse outcomes of SVG PCI.

Abciximab↗

Rationale for intracoronary administration of abciximab.

The present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab, an antiplatelet drug used in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Abciximab is a glycoprotein (GP) IIb/IIIa receptor antagonist which determines a potent inhibition of platelet aggregation and thrombus formation. These properties seem to prevent not only thrombus formation but also to promote (at higher drug concentration) lysis of fresh thrombus. Moreover, differently from the other GP IIb/IIIa inhibitors, abciximab also binds to the vitronectin receptor on endothelial, smooth muscle, and inflammatory cells and to an activated conformation of the aMb2 receptor on leukocytes. Such cross-reactivity raises the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways involving platelets, white blood cells, and the vascular endothelium. On such basis, the local administration of abciximab at the site of coronary thrombosis may enhance, by increasing its local concentration, the binding to both platelet and endothelium receptors. The results of several angiographic studies assessing the effect of intracoronary abciximab administration support on clinical grounds its adoption in patients with fresh coronary thrombosis. Indeed, better post-angioplasty coronary flow, greater degree of myocardial salvage and a better left ventricular function recovery have been achieved as compared to the intravenous, systemic, administration of drug's bolus. Condensed Abstract Several studies have highlighted the benefits of abciximab, a potent antiplatelet agent, in patients with acute coronary syndromes undergoing percutaneous coronary interventions. Moreover, differently from the other glycoprotein IIb/IIIa receptor antagonists, abciximab also has non-IIb/IIIa-related properties raising the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways. Several angiographic studies in patients with fresh coronary thrombosis and recent clinical studies in patients with acute coronary syndromes undergoing mechanical revascularization support the hypothesis that local administration of abciximab at the site of the culprit coronary artery may facilitate both the de-thrombotic and the non-GP IIb/IIIa-dependent properties of the drug. On such basis, the present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab.

Abciximab↗