Impaired plasminogen binding in patients with venous thromboembolism : association with protein carbonylation

Abstract Introduction Venous thromboembolism (VTE) is associated with hypofibrinolysis. Its mechanisms are poorly understood. We investigated plasminogen-fibrin interaction and its association with fibrinolytic capacity and protein oxidation/carbonylation in VTE patients. Materials and methods Plasma-purified plasminogen conversion to plasmin and surface plasmon resonance employed for plasminogen-fibrin interactions were individually evaluated in all healthy controls and non-anticoagulated patients following VTE, 10–23 months since the event. We also assessed plasma fibrin clot permeability (K s ), clot lysis time (LT), activators and inhibitors of fibrinolysis together with oxidation/carbonylation markers. Results VTE patients had impaired plasminogen binding to fibrin (apparent Kd, + 290%, p  = 0.002), reduced rate of plasmin generation (− 4.7%, p  = 0.001), and longer LT (+ 18.6%, p s were similar in both groups. Apparent Kd correlated with LT ( r  = 0.43, p  = 0.037), tissue plasminogen activator-plasminogen activator inhibitor 1 (tPA-PAI-1) complexes ( r  = 0.63, p  = 0.012), and active PAI-1 ( r  = 0.49, p  = 0.03). Compared with controls, VTE patients had higher thiobarbituric acid reactive substances (TBARS), total protein carbonyl content (PC), and lower total antioxidant capacity (all p r  = 0.61, r  = 0.56, and r  = − 0.47, respectively, all p r  = 0.48, p  = 0.032) and PC ( r  = 0.54, p  = 0.013) in the whole group. Conclusions Plasminogen-fibrin interactions are altered in young and middle-aged VTE patients, without known thrombophilias, except increased factor VIII. The mechanisms underlying these phenomena remain to be established.