THE INDIVIDUAL FIBRINOLYTIC CAPACITY PREDICTS EFFICACY OF ULTRASOUND-ASSISTED CATHETER-DIRECTED THROMBOLYSIS IN PATIENTS WITH ACUTE PULMONARY EMBOLISM.

Abstract

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. The aim of this study was to identify predictive markers for the efficacy of USAT in patients with acute PE.

Patients/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 obtained from 35 patients before treatment start, at 6 hours (during infusion of rt-PA), as well as at 24 hours after treatment start (post-lysis). The hemostatic properties were evaluated with thromboelastometry, assessment of fibrinolytic markers, and the ex vivo capacity of rt-PA-spiked plasma to generate the plasmin-antiplasmin (plap) complex.

Results: Patients presented with an elevated mean pulmonary artery pressure (PAPm; 32.9 ± 7.6 mmHg), with a post-lysis reduction of 9.4 ± 8.3 mmHg on average, yet the treatment response varied markedly across individuals. The endogenous fibrinolytic capacity, as represented by plap complex and D-dimer levels as well as consumption of the endogenous fibrinolysis inhibitor α2-antiplasmin at 6 hours predicted the individual treatment efficacy, indicated by the reduction in PAPm (all p<0.05). Furthermore, ex vivo assessment of the fibrinolytic potential before start of USAT also predicted efficacy. Both, ML INTEM, as well as the novel parameter fibrin-sensitivity ratio were identified as predictors for USAT responsiveness (both p<0.05).

Conclusions: Markers of fibrinolysis may be harnessed to predict treatment responsiveness to USAT in acute PE patients.