Abstract
BackgroundAspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF.MethodsWe included 177 stable coronary artery disease patients on aspirin monotherapy. Among these, 116 (66%) had ATF defined as myocardial infarction (MI) whilst on aspirin. Platelet aggregation was assessed by Multiplate® aggregometry and VerifyNow®, whereas turbidimetric assays and scanning electron microscopy were employed to study fibrin clot characteristics.ResultsEnhanced platelet aggregation was observed in patients with ATF compared with non-MI patients following stimulation with arachidonic acid 1.0 mM (median 161 (IQR 95; 222) vs. 97 (60; 1776) AU*min, p = 0.005) and collagen 1.0 µg/mL (293 (198; 427) vs. 220 (165; 370) AU*min, p = 0.03). Similarly, clot maximum absorbance, a measure of fibrin network density, was increased in patients with ATF (0.48 (0.41; 0.52) vs. 0.42 (0.38; 0.50), p = 0.02), and this was associated with thinner fibres (mean ± SD: 119.7±27.5 vs. 127.8±31.1 nm, p = 0.003) and prolonged lysis time (552 (498; 756) vs. 519 (468; 633) seconds; p = 0.02). Patients with ATF also had increased levels of C-reactive protein (CRP) (1.34 (0.48; 2.94) and 0.88 (0.32; 1.77) mg/L, p = 0.01) compared with the non-MI group. Clot maximum absorbance correlated with platelet aggregation (r = 0.31–0.35, p-values<0.001) and CRP levels (r = 0.60, p<0.001).ConclusionsPatients with aspirin treatment failure showed increased platelet aggregation and altered clot structure with impaired fibrinolysis compared with stable CAD patients without previous MI. These findings suggest that an increased risk of aspirin treatment failure may be identified by measuring both platelet function and fibrin clot structure.
Highlights
Rupture of an atherosclerotic plaque causes platelet aggregation and activation of the coagulation cascade with formation of thrombin prompting conversion of fibrinogen to fibrin
Patients with previous myocardial infarction (MI) whilst on aspirin were three years older than patients without previous MI, and they more frequently had a history of percutaneous coronary intervention and treatment with ACE inhibitors and insulin
Serum thromboxane B2 (TXB2) did not differ between nonMI patients and patients with previous MI neither before nor after adjustment for age, fibrinogen, platelet count, ACE inhibitors, diuretics, and insulin (p = 0.19 and p = 0.20, respectively)
Summary
Rupture of an atherosclerotic plaque causes platelet aggregation and activation of the coagulation cascade with formation of thrombin prompting conversion of fibrinogen to fibrin. Studies have shown that altered structure of fibrin clots is associated with coronary artery disease (CAD) and myocardial infarction (MI) [3,4,5,6,7,8]. Increased plasma levels of fibrinogen directly modulate fibrin clot properties and compromise fibrinolysis, representing one mechanism explaining the association between fibrinogen levels and cardiovascular disease. Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF
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