Thrombin‐activatable fibrinolysis inhibitor in human abdominal aortic aneurysm disease

Abstract

Background Intra-luminal thrombosis is a key factor in growth of abdominal aortic aneurysms (AAAs). Patients with AAA form dense clots that are resistant to fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) has been shown to influence AAA development in murine models. Objective The aim of this study is to characterize the role of TAFI in human AAA. Methods Plasma levels of TAFI, TAFI activation peptide (TAFI-AP), activated/inactivated TAFI (TAFIa/ai) and plasmin-α2-antiplasmin complex were measured by ELISAs in patients with AAA (n=202) and controls (n=188). Results TAFIa/ai and TAFI-AP levels were higher in patients than controls (median [IQR], 20.3 [14.6-32.8]ngmL-1 vs. 14.2 [11.2-19.3]ngmL-1 and 355.0 [232.4-528.1]ngmL-1 vs. 248.6 [197.1-328.1]ngmL-1 ). TAFIa/ai was positively correlated with TAFI-AP (r=0.164). Intact TAFI levels were not different between patients and controls (13.4 [11.2-16.1]μgmL-1 vs. 12.8 [10.6-15.4]μgmL-1 ). Plasmin-α2-antiplasmin was higher in AAA patients than controls (690.0 [489.1-924.3]ngmL-1 vs. 480.7 [392.6-555.3]ngmL-1 ). Conclusions The increase in TAFIa/ai and TAFI-AP suggests an increased TAFI activation in patients with AAA. Prospective studies are required to further elucidate the role of TAFI and fibrinolysis in AAA pathogenesis.