Thrombin Generation and Activity During Coronary Angioplasty: Influence of Angiographic Lesion Morphology

OBJECTIVE: To investigate the relationships between coronary atherosclerotic plaque injury, lesion morphology, and activation of the coagulation cascade. BACKGROUND: Balloon angioplasty of coronary lesions may result in intracoronary thrombin generation and activity. It is unknown whether the angiographic morphology of the lesion prior to intervention, an indicator of the presence of thrombus in the lesion, is a determinant of the degree of coagulation cascade activation. METHODS AND RESULTS: Biochemical markers of thrombin generation (prothrombin fragment F1+2) and thrombin activity (fibrinopeptide A; FPA) were measured in coronary blood before, 1 and 10 minutes after percutaneous transluminal coronary angioplasty (PTCA) in 24 patients with an angiographically complex lesion morphology and 24 patients with an angiographically simple lesion morphology. Using previously defined criteria, 18 of the 48 patients (38%) demonstrated a significant rise in coronary plasma F1+2; 8 of these 18 (44%) had simple and 10 of 18 (55%) had complex angiographic lesion morphologies (p=NS). With respect to thrombin activity, 15 of the 48 patients (31%) demonstrated a significant rise in coronary plasma FPA; 7 of these 15 patients (47%) had a simple lesion morphology and 8 (53%) had a complex morphology (p=NS). When analyzed as a group, patients with complex lesion morphologies demonstrated a small elevation in coronary plasma levels of FPA 10 minutes post-PTCA (median 3.2 ng/ml, 95% CI 2.4D5.8 ng/ml) in comparison to the levels measured proximal to the lesion pre-PTCA (median 2.1 ng/ml, 95% CI 1.6D3.5 ng/ml; p=0.05). In contrast, in the group of patients with simple lesion morphologies, the plasma FPA levels proximal to the lesion pre-PTCA (median 2.1 ng/ml, 95% CI 1.5 to 3.9 ng/ml) were similar to those measured 10 minutes after the procedure (median 2.0 ng/ml, 95% CI 1.5 to 6.3 ng/ml; p=NS). CONCLUSIONS: In comparison to patients with angiographically complex lesions, patients with angiographically simple lesions demonstrate a similar incidence (~33%) of elevated coronary plasma thrombin generation (F1+2) and activity (FPA) after PTCA. As a group, patients with angiographically complex lesions (irregular borders, overhanging edges, filling defects) demonstrate a slightly greater increase in thrombin activity in comparison to patients with simple lesion morphologies. Percutaneous coronary interventions of lesions with a wide variety of angiographic morphologies are prone to result in activation of the coagulation cascade.