Assessment of platelets and the endothelium in patients presenting with acute coronary syndromes – is there a future?

Derhaschnig, Ulla; Jilma, Bernd

doi:10.1160/th09-07-0427

Cited by 11 publications

(11 citation statements)

References 66 publications

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“…PFA-100 is a well established test system for platelet function [20] and short CT values are associated with myocardial damage and outcome in patients with ACS [34][35][36][37][38]. Further, short CT values appear to predict future cardiovascular events in patients suffering from coronary artery disease or peripheral arterial occlusive disease (PAOD) [16,21,39,40]. Moreover, PFA-100 is a sensitive tool to detect COX-1 inhibition which prolongs CEPI-CT [20,40,41].…”

Section: Discussionmentioning

confidence: 99%

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Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia

Derhaschnig

Schweeger-Exeli²,

Marsik³

et al. 2010

Platelets

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Acetylsalicylic acid (ASA) prevents thromboembolic events by inhibiting platelet function through blocking of cyclooxygenase type 1 (COX-1). A nitroderivate of ASA, 2-(acetyloxy)benzoic acid 3-(nitrooxymethyl)-phenyl ester (NCX 4016) was synthesized, which additionally acts through nitric oxide release. In various in vitro and animal studies NCX 4016 exhibited antithrombotic and anti-platelet properties. We used the standardized model of endotoxin infusion into human volunteers to compare the effects of NCX 4016 and ASA on platelet function and TF-induced coagulation activation. The trial consisted of two parts. In the first part, 10 healthy male volunteers were included in a randomized, open cross-over trial to find a NCX formulation with optimal tolerability and pharmacokinetic data were obtained. The second part was a randomized, double blind placebo controlled clinical trial consisting of 30 healthy male volunteers in three parallel groups (n = 10 per group). Volunteers received either NCX 4016 (800 mg b.i.d.), ASA (425 mg b.i.d.) or placebo for 7 days, before infusion of 2 ng/kg endotoxin on day 8. ASA attenuated the endotoxin-induced platelet plug formation (measured by PFA-100) significantly better than NCX 4016 and placebo (p < 0.004), while there was no difference in soluble P-selectin or VWF-levels. Urine 11-dehydro-thromboxane B(2) levels were significantly lower in the ASA and NCX 4016 groups as compared to placebo (p < 0.05). Neither ASA nor NCX 4016 significantly changed prothrombin fragment(1 + 2), D-Dimer or tissue factor (TF)-mRNA levels. In summary, NCX 4016 had no effect on VWF release, platelet activation as measured by soluble P-selectin or TF gene expression. NCX 4016, at the dose tested, unlike ASA, had no effect on platelet collagen/epinephrine induced plug formation under high shear rates.

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Section: Discussionmentioning

confidence: 99%

“…C-reactive protein (CRP) values were determined by nephelometry (Tina-quant Õ CRP, Boehringer Mannheim/Hitachi, FRG). VWF is an established cardiovascular risk marker [16][17][18]. VWF:RCo was assayed by turbidometry using a commercial kit from Behring (Marburg, Germany) consisting of lyophilized platelets and ristocetin [18].…”

Section: Main Trial (Part Ii)mentioning

confidence: 99%

Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia

Derhaschnig

Schweeger-Exeli²,

Marsik³

et al. 2010

Platelets

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“…Nevertheless, the relationship between PON1 activity (paraoxonase and arylesterase activity) and non-diabetic SCAD remains poorly understood. Von Willebrand factor (VWF) may be a signal of endothelial impairment because it can be released from endothelial cells to facilitate platelet adhesion and aggregation at sites of injury [ 10 , 11 ]. VWF is released predominantly in response to a rise in cytosolic free calcium and cyclic adenosine monophosphate (cAMP) levels.…”

Section: Introductionmentioning

confidence: 99%

Low Paraoxonase 1 Arylesterase Activity and High von Willebrand Factor Levels are Associated with Severe Coronary Atherosclerosis in Patients with Non-Diabetic Stable Coronary Artery Disease

et al. 2014

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BackgroundParaoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes.Material/MethodsNon-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative.ResultsBoth PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all P<0.001). PON1 paraoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase.ConclusionsPON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.

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“…Under healthy conditions, vascular endothelium releases prostacyclins and nitric oxide, which attenuate platelet response. In acute plaque rupture, injury to vascular endothelium occurs, thereby exposing subendothelial proteins, including collagen and von Willebrand factor that recruit localised platelets and promote platelet activation (2,3). Tissue factor is released resulting in coagu-lation activation (4).…”

Section: Clopidogrel: Mechanism Of Actionmentioning

confidence: 99%

Clopidogrel in acute coronary syndromes: Where are we now?

Bainey

Lai²,

Mehta³

2011

Thromb Haemost

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Assessment of platelets and the endothelium in patients presenting with acute coronary syndromes – is there a future?

Cited by 11 publications

References 66 publications

Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia

Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia

Low Paraoxonase 1 Arylesterase Activity and High von Willebrand Factor Levels are Associated with Severe Coronary Atherosclerosis in Patients with Non-Diabetic Stable Coronary Artery Disease

Clopidogrel in acute coronary syndromes: Where are we now?

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