Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms

摘要

Background: The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (Al) and thin (Bl) segments of ILTs and aneurysm wall sections A (adjacent to Al) and B (adjacent to Bl) from one aneurysm sac were taken from 35 patients undergoing elective repair. Methods: Factor levels were measured using enzyme-linked immunosorbent assay of protein extract.Results: Tissue factor (TF) activities were significantly higher in thinner segments of AAA (Bl vs Al, P= .003; B vs A, P < .001; B vs Al, P< .001; B vs Bl, P= .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, Al, and Bl (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of a_2-antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P= .021) and thick ILT (Al; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (Al). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). Conclusions: These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Clinical Relevance: Intraluminal thrombus (ILT) and abdominal aortic aneurysm wall thickness vary significantly across each individual aneurysm. The study suggests that intensified coagulation and probably local fibrinolysis in thin ILT segments may be part of a chain reaction leading to the destruction of the aneurysm wall and, as a result, its rupture. Considering the significant ability of coagulative and fibrinolytic systems to construct ILT as well as to regulate extracellular matrix proteolysis of the abdominal aortic aneurysm wall, the spatiotemporal distribution of components of these two systems represents data that may improve patient-specific models of aneurysmal progression and rupture risk in the future.