An assay that informs precision-based intrapleural fibrinolytic therapy (IPFT) is disclosed. Provided is a simple assay based on measurement of the Fibrinolytic Potential (FP)—total fibrinolytic activity in pleural fluid when plasminogen activator inhibitors (PAIs) are neutralized and endogenous plasminogen (PLG) is activated. The assay is used to determine FP in baseline pleural fluids of patients undergoing IPFT with agents such as tPA or scuPA to determine the dose and dose intervals for the particular patient. Pleural fluids are also collected after IPFT to confirm that intrapleural fibrinolysis is inhibited and endogenous PLG accumulates in the pleural fluid. Inhibition of intrapleural fibrinolysis in combination with its increase after supplementation of pleural fluid with a plasminogen activator indicates whether or not the subject should be treated with more or higher doses of an IPFT drug.