The individual fibrinolytic capacity predicts the efficacy of ultrasound-assisted catheter-directed thrombolysis in patients with acute pulmonary embolism

Background: Ultrasound-assisted catheter-directed thrombolysis (USAT) is nowadays available as an alternative reperfusion approach for acute pulmonary embolism (PE). The lytic agent recombinant tissue-type plasminogen activator (rt-PA) activates the effector protease plasmin to induce fibrinolysis. Objectives: The aim of this study was to identify predictive markers for the efficacy of USAT in patients with acute PE. Methods: In a single-center cohort study of USAT for intermediate-high or high-risk PE, pulmonary-arterial hemodynamic measurements were performed, and plasma samples were obtained from 35 patients before treatment start, at 6 hours (during infusion of rt-PA), and at 24 hours after treatment start (postlysis). The hemostatic properties were evaluated with thromboelastometry, and fibrinolytic markers and the ex vivo capacity of rt-PA-spiked plasma to generate the plasmin-antiplasmin complex were assessed. Results: Patients presented with an elevated mean pulmonary artery pressure (32.9 +/- 7.6 mm Hg), with an average postlysis reduction of 9.4 +/- 8.3 mm Hg, yet the treatment response varied markedly across individuals. The endogenous fibrinolytic capacity, as represented by the plasmin-antiplasmin complex and D-dimer, as well as consumption of the endogenous fibrinolysis inhibitor alpha 2-antiplasmin at 6 hours, predicted the individual treatment efficacy, indicated by the reduction in mean pulmonary artery pressure (all P < .05). Furthermore, ex vivo assessment of the fibrinolytic potential before the start of USAT also predicted efficacy. Both maximum clot lysis INTEM and the novel parameter fibrin-sensitivity ratio were identified as predictors of USAT responsiveness (both P < .05). Conclusion: Markers of fibrinolysis may be harnessed to predict treatment responsiveness to USAT in patients with acute PE.