Abstract
Introduction: Fibrin is a major component of intracoronary thrombus obtained during ST-elevation myocardial infarction (STEMI). Apart of the time of ischemia determinants of intracoronary thrombus composition are largely unknown. Hypothesis: We sought to investigate whether ex-vivo measured plasma fibrin clot properties are associated with intracoronary thrombus ultrastructure. Methods: In the intracoronary thrombus aspirated from 80 of the 156 consecutive STEMI patients within 12 hours since symptom onset, we assessed the content of fibrin, erythrocytes and platelets and thrombus heterogeneity by scanning electron microscopy. On admission plasma fibrin clot permeability (Ks), which indicates pore size, clot lysis time (t50%), platelet reactivity index (PRI) and aggregation induced by 5 μM of adenosine diphosphate (ADP) were correlated with intracoronary thrombus composition. Results: All patients received 300 mg of aspirin and 45 (56.3%) 600 mg of clopidogrel, 70 (41-120) min prior to aspiration. PRI inversely correlated (r=-0.24, P=0.035) with the time elapsed since clopidogrel pretreatment. The median content of fibrin, erythrocytes and platelets in intracoronary thrombus was 49.1 (25.0-72.6)%, 29.0 (4.8-57.7)% and 6.8 (1.0-15.1)%, respectively. Fibrin content was correlated with baseline Ks (r=-0.45, P<0.0001), t50% (r=0.32, P<0.0001), fibrinogen (r=0.32, P<0.0001), the time to opening of infarct-related artery (r=0.24, P<0.001), reference lumen diameter of infarct-related artery (r=0.15, P<0.001), but not with PRI and ADP-induced platelet aggregation. Fibrin content was higher in patients without pre-hospital loading with clopidogrel (58 vs. 43%, P<0.0001), treated with aspirin prior to STEMI (62 vs. 47%, P<0.0001) or with positive family history of coronary artery disease (62 vs. 46%, P=0.0004). Multiple regression analysis adjusted for age and fibrinogen showed that Ks, time of ischemia and clopidogrel pretreatment independently predicted fibrin content in intracoronary thrombus (R2=0.44, P<0.0001). Conclusion: Formation of denser fibrin clots displaying resistance to lysis, and clopidogrel pretreatment contributed to fibrin content within the intracoronary thrombus during an acute phase of STEMI.
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