Markers of endothelial and platelet activation are associated with high on-aspirin platelet reactivity in patients with stable coronary artery disease.

Abstract

INTRODUCTION:

Aspirin inhibits the cyclooxygenase-1 (COX-1) mediated thromboxane A2 synthesis. Despite COX-1 inhibition, in patients with coronary artery disease (CAD), platelets can be activated through other mechanisms, like activation by thrombin.

MATERIALS AND METHODS:

At baseline in this cross-sectional substudy of the ASCET trial, 1001 stable CAD patients, all on single aspirin treatment, were classified by the PFA100® method, as having high on-aspirin residual platelet reactivity (RPR) or not. Markers of hypercoagulability, endothelial and platelet activation as related to RPR, were evaluated to explore the potential mechanisms behind high on-aspirin RPR.

RESULTS:

Altogether, 25.9% (n=259) of the patients were found to have high on-aspirin RPR. S-thromboxane B(2) levels were very low and did not differ between patients having high on-aspirin RPR or not. Patients with high on-aspirin RPR had significantly higher levels of von Willebrand Factor (vWF) (124 vs 100%, p<0.001, platelet count (236 vs 224 × 10(9)/l, p=0.008), total TFPI (68.4 vs 65.5 ng/ml, p=0.005) and ß-thromboglobulin (ß-TG) (33.3 vs 31.3 IU/ml, p=0.041) compared to patients with low on-aspirin RPR. No significant differences between the groups were observed in levels of endogenous thrombin generation (ETP), pro-thrombin fragment 1+2 (F1+2), D-dimer, soluble TF (sTF) or P-selectin (all p>0.05).

CONCLUSIONS:

The high on-aspirin RPR as defined by PFA100® seems not to be due to increased thrombin activity as evaluated with ETP, sTF, F1+2 or D-dimer. The elevated levels of platelet count, ß-TG, TFPI and especially vWF might be explained by increased endothelial and platelet activation in these patients.

• Authors: Alf-Åge R Pettersen, Harald Arnesen, Trine B Opstad, Vibeke Bratseth, Ingebjørg Seljeflot
• Journal: Thrombosis research (Thromb Res) Vol. 130 Issue 3 Pg. 424-8 (Sep 2012) ISSN: 1879-2472 [Electronic] United States
• PMID: 22795340 (Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• Blood Coagulation Factors
• Platelet Aggregation Inhibitors
• Aspirin

Topics

• Adult
• Aged
• Aspirin (administration & dosage)
• Biomarkers (blood)
• Blood Coagulation Factors (analysis)
• Coronary Artery Disease (blood, drug therapy, epidemiology)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Norway (epidemiology)
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Platelet Count
• Platelet Function Tests (statistics & numerical data)
• Prevalence
• Reproducibility of Results
• Sensitivity and Specificity