The interaction of fibrinolysis and the complement system in patients with acute pulmonary embolism, treated with ultrasound-assisted catheter-directed thrombolysis

Ultrasound-assisted catheter-directed thrombolysis (USAT) with recombinant tissue-type plasminogen activator (rt-PA) is widely used as a reperfusion approach for acute pulmonary embolism (PE). The fibrinolytic effector protease plasmin is known to be a potent activator of the complement system. The aim of this study was to better characterize the extent of complement activation during USAT, and its relationship with the fibrinolytic system.In this single-center cohort study of USAT for PE, pulmonary-arterial hemodynamic measurements were performed, and plasma samples obtained from 35 patients before treatment start and at 6 hours (during infusion of rt-PA). Hemostatic properties were evaluated with thromboelastometry and assessment of fibrinolytic markers. In addition, levels of the complement components C3a, C4a, C5a, soluble C5b-9 (sC5b-9), Ba, Bb, factor H and factor I at these time points were determined.Several complement components, including the anaphylatoxin C3a, showed a reduction during USAT. We found a positive correlation of the plasmin-antiplasmin complex (plap complex) with factor H, yet a negative correlation with both Ba and Bb, C5a and sC5b-9. The potent plasmin-inhibitor, α2-antiplasmin, displayed a positive correlation with Ba and Bb, factor I and factor H. In addition, the anaphylatoxin C5a negatively, and Ba positively predicted treatment responsiveness to USAT.In conclusion, in the setting of acute PE and reperfusion therapy with USAT, there appears to be a competing effect between plasmin-mediated complement activation and a reduction of the inflammatory trigger by resolution of obstruction and ischemia. Complement activation in PE is downregulated during USAT, an effect exceeding the complement-activating properties of plasmin.