Understanding the systemic effects of intrapleural tPA and DNase by evaluating effects on coagulation

Complicated parapneumonic effusions and empyemas are common presentations that carry significant morbidity and mortality. Standard therapy includes antibiotics and chest tube placement. Due to the nature of the fluid, it is often difficult to drain completely using a chest tube. As outlined in multiple studies, intrapleural tissue plasminogen activator (tPA) and dornase alfa (DNase) are effective at helping clear these effusions and the avoidance of surgery. Despite research to better understand the effectiveness of the treatment and possible side effects, there continues to be a lack of data on potential systemic effects.

This prospective observational pilot study was conducted from May 2021 until June 2022. Basic demographics, complications, prothrombin time, activated partial thromboplastin time, D-Dimer, fibrinogen, and thromboelastography scans were measured both before and after infusion of chest tube tPA and DNase to assess for differences in coagulation using Signed Rank tests.

A total of 17 patients were enrolled in the study. Two patients were excluded due to protocol deviations. The median change score for lysis of clot at 30 minutes (Ly30), our primary outcome of interest, was 0 (P=0.88). There were no significant changes in other coagulation measures when comparing pre and post treatment. One patient (5.9%) had intrapleural bleeding associated with therapy. Three patients (17.6%) underwent surgical intervention to further treat their complicated pleural effusion.

This is the first study to evaluate measurable changes in systemic coagulation after intrapleural tPA and DNase. Our data demonstrates no significant difference in coagulation after intrapleural tPA and DNase infusion, suggesting that there may not be clinically significant absorption.