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: 3.13). 11/2009; 126(3):254-7. DOI: 10.1016/j.thromres.2009.11.010
Source: PubMed
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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; · 6.18 Impact Factor
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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; · 6.08 Impact Factor
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    ABSTRACT: We evaluated the relationship between antithrombotic effects and pharmacodynamic (PD) marker changes produced by the novel factor (F)Xa inhibitors darexaban (YM150) and rivaroxaban in a rabbit model of plaque disruption-induced arterial thrombosis. Animals were subjected to catheter-induced endothelial denudation via the femoral artery followed by a two-week high-cholesterol diet. Plaque disruption was induced by balloon angioplasty, and then stasis was achieved by ligation at the distal side of the injured segment. Darexaban and rivaroxaban were administered orally 1 hour (h) before and 9 h after plaque disruption, and their antithrombotic effects were evaluated 24 h after the initiation of ligation. Prothrombin time (PT), activated partial thromboplastin time (APTT), and plasma FXa activity were measured using blood samples collected before and 1h after administration. Darexaban and rivaroxaban significantly reduced thrombus formation. The thrombus weight obtained in the 30 mg/kg darexaban group was comparable to that in the 1 mg/kg rivaroxaban group (2.17 ± 0.63 and 3.23 ± 1.64 mg, respectively, vs. 8.01 ± 1.08 mg in the control group). Plasma FXa activity correlated with the antithrombotic effects of darexaban and rivaroxaban, while PT only correlated with those of darexaban. Our findings suggest that the degree of plasma FXa inhibition may be useful for predicting antithrombotic effects of darexaban and rivaroxaban in arterial thrombosis. PT may also be useful in evaluating antithrombotic effects of darexaban in particular.
    Thrombosis and Haemostasis 10/2012; 108(5). · 5.76 Impact Factor