Composition of thrombi in late drug-eluting stent thrombosis versus de novo acute myocardial infarction

Department of Cardiology, Miyazaki Medical Association Hospital, and Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Thrombosis Research (Impact Factor: 2.43). 11/2009; 126(3):254-7. DOI: 10.1016/j.thromres.2009.11.010
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    ABSTRACT: Background: Despite standard dual antiplatelet therapy (DAT; acetylsalicylic acid [ASA] and clopidogrel), there is a ≥1.4% incidence of in-stent thrombosis in patients with acute coronary syndrome. Factor Xa inhibitors are being investigated for secondary prevention after acute coronary syndrome. Objective: To study the antithrombotic effects of the factor Xa inhibitor rivaroxaban alone or in combination with DAT. Methods: Bare metal stents (12 per animal, three per intervention period) were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood (shear rate: 1500 s(-1) ). In-stent thrombus formation was analyzed under different treatments: vehicle (n = 7 animals); intravenous (i.v.) rivaroxaban 0.11, 0.33, and 1.0 μg kg(-1 ) min(-1) (n = 8); rivaroxaban + ASA (1.0 mg kg(-1) i.v.) (n = 6); rivaroxaban + ASA (1.0 mg kg(-1) i.v.) + clopidogrel (0.5 mg kg(-1) i.v.) (n = 7); and ASA (1.0 mg kg(-1) i.v.) + clopidogrel (0.5 mg kg(-1) i.v.) (n = 6). Results: Rivaroxaban dose-dependently reduced stent thrombus weight by ≤66% versus vehicle (P < 0.05, all doses). Rivaroxaban + ASA further reduced thrombus weight versus vehicle (86% at highest rivaroxaban dose; P < 0.001). DAT reduced thrombus weight by ≤79%. However, rivaroxaban + ASA + clopidogrel almost completely abolished in-stent thrombus formation (98% reduction versus vehicle at highest rivaroxaban dose; P < 0.001). Conclusions: Our data on the inhibitory effect of rivaroxaban alone or with DAT are consistent with the ATLAS 2 trial findings and support its potential use for preventing stent thrombosis after stent deployment. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 10/2012; 10(12). DOI:10.1111/jth.12033 · 6.08 Impact Factor
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    ABSTRACT: Background: Thrombus propagation on disrupted atherosclerotic plaque leads to acute myocardial infarction (AMI). Recent studies have shown that the histopathology of the coronary thrombus is associated with myocardial reperfusion, ST-segment recovery, distal embolization and long-term mortality in patients with AMI. Therefore, we investigated the histopathologic characteristics of material aspirated during percutaneous coronary intervention (PCI) in patients with AMI, and assessed whether the histologic findings are related to in-hospital mortality. Methods and Results: In this prospective single-center registry, coronary materials were obtained during PCI from 264 AMI patients within 24h of the onset of anginal symptoms. Organized thrombus, calcification and plaque components in the aspirated material were morphologically assessed. In-hospital deaths occurred in 17 (6%) patients. Organized thrombi were found in 91 (34%) of 264 patients, calcification was identified in 44 (17%) and plaque components in 117 (44%) patients. Rates of in-hospital all-cause mortality were significantly higher among patients with than without organized thrombus (P<0.05). Multivariate analysis also identified organized thrombus as an independent predictor of in-hospital death, as well as age, a history of myocardial infarction and the presence of shock (P<0.05). In contrast, calcification and plaque components were not significantly associated with in-hospital mortality. Conclusions: Our results suggest that organized thrombus in aspirated coronary material is an independent predictor of in-hospital mortality of patients with AMI.
    Circulation Journal 02/2013; 77(5). DOI:10.1253/circj.CJ-12-0911 · 3.69 Impact Factor
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    ABSTRACT: Intracoronary thrombus is a source of active lipid mediators including eicosanoids that play a critical role in the pathogenesis of acute myocardial infarction (AMI). Eicosanoids are derived from arachidonic acid generated by phospholipase A2 (PLA2). This study examined whether PLA2 is expressed in the aspirated coronary thrombus and whether PLA2 expression in the thrombus may be related to recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery after AMI. Intracoronary thrombus was obtained using an aspiration catheter from 48 patients with AMI, who had successful emergent treatment with percutaneous coronary intervention (PCI). Repeated intravascular ultrasound in the culprit coronary artery was performed at emergent PCI and 6months later in a subgroup of 20 patients. There was a higher prevalence of cells in the thrombus that were immunopositive to group IIA, IVA, V and X PLA2s in patients with (n=11) than without (n=37) cardiac events during 6months of follow-up (P<0.05 for all). The prevalence of the cells that were immunopositive to group IIA, IVA and V PLA2s in the thrombus was significantly associated with the percent increase in atheroma volume (r=0.60, 0.55 and 0.45, respectively, P<0.05 for all) after 6months in the native coronary segment distal to the culprit coronary lesion. PLA2 expression in coronary thrombus is associated with recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery in AMI survivors.
    International journal of cardiology 08/2013; 168(4). DOI:10.1016/j.ijcard.2013.07.154 · 6.18 Impact Factor