Abstract / Summary
Background/Objectives: Intrapleural fibrinolytic therapy (IPFT) reduces treatment failure and the need for surgery in complex pleural effusions (CPEs). Side effects, particularly systemic bleeding, are poorly characterised. The primary outcome of this review is the change in systemic coagulation/fibrinolytic markers post-IPFT with a secondary outcome of pleural and systemic complications. Methods: A systematic search was conducted up to March 2026 in Medline, Embase, and Cochrane Central (PROSPERO:CRD42024532865) to include RCTs, non-randomised studies, and case reports of adults with CPEs treated with IPFT that reported effects on systemic coagulation/fibrinolysis or complications. Quality was assessed using Cochrane tools. Results: A total of 147 studies were included: 20 RCTs, 34 prospective, 53 retrospective and 40 case reports (n = 9226; 3004 female). The majority (84%) had pleural infections. Coagulation/fibrinolytic markers pre- and post-IPFT were reported in 15 studies, of which only two case reports noted elevated coagulation markers associated with bleeding. In 82 studies using tissue plasminogen activator (n = 5402), the adverse event rates were 11.4%, 4.8%, and 0.4% for chest pain, pleural bleeding, and systemic bleeding, respectively. Fifteen case reports described severe complications including systemic haemorrhage, cerebral air embolism, or death. Chest pain, pleural bleeding and fever are the most common IPFT complications. Systemic bleeding is rare. Most studies reporting systemic bleeding did not assess coagulation/fibrinolysis markers. Conclusions: Evidence remains insufficient to determine associations between coagulation marker changes and systemic bleeding post-IPFT.