Indwelling pleural catheters (IPCs) are effective management options for malignant pleural effusion. Symptomatic fluid loculation is a recognized complication of IPC use and is usually managed with intrapleural instillation of fibrinolytic drugs, such as tissue plasminogen activator (tPA). A previous multicentre observational study showed significant heterogeneity among centres in their dosing regimen for tPA (from 2 to 20 mg) in treating symptomatic loculations. Potential pleural bleeding, especially in high-risk patients, often deters clinicians from initiating intrapleural fibrinolytic therapy. Lower doses of tPA may reduce bleeding risks. This case report describes the successful use of 0.5 mg (the lowest reported dose) of tPA in a patient with significant bleeding risks whose IPC was complicated by symptomatic loculation.