Safety and Effectiveness of a High‐Dose, Tailored Tissue Plasminogen Activator Therapy Protocol: A Joint Pediatric Hematology and Cardiac ICU Quality Improvement Initiative Analysis

BACKGROUND: Pediatric thromboembolism is increasingly encountered in critical care. Systemic thrombolysis with tissue plasminogen activator (tPA) facilitates vessel or valve patency, yet pediatric-specific protocols remain undefined, and safety concerns persist. OBJECTIVE: To evaluate the efficacy and safety of a tailored, prolonged systemic tPA protocol for vessel thrombosis and mechanical valve obstruction in infants and children, and to characterize D-dimer kinetics by indication. METHODS: This retrospective cohort study was performed in a tertiary pediatric cardiac ICU (from July 2014 to March 2024). Extracted data included demographics, tPA dosing, laboratory trends, transfusion requirements, imaging-confirmed success, and adverse events. D-dimer trajectories were analyzed using Welch's t-test. RESULTS: Twenty-two patients received systemic tPA during the study period. Median age was 287 days (IQR: 64.8-940); 32% were less than 90 days old. Indications included stuck mechanical valve (n = 10), central venous thrombosis with chylothorax (n = 7), large venous thrombosis (n = 3), coronary thrombosis (n = 1), and arterial ischemic stroke (n = 1). Median initial tPA dose was 0.1 mg/kg/h (IQR: 0.06-0.1), with escalation up to 0.5 mg/kg/h in selected cases; mean treatment duration was 3.9 ± 2.8 days. Valve mobility was restored in 80%. Complete thrombus resolution was achieved in all venous, coronary, and stroke cases. Minor bleeding occurred in 23%; one subdural hemorrhage (5%) was observed. All patients survived to discharge. D-dimer kinetics differed significantly between vessel thrombosis and mechanical valve obstruction (p < 0.01), demonstrating distinct fibrinolytic profiles. CONCLUSIONS: Tailored prolonged systemic tPA appears effective with minimal adverse effects when administered under strict monitoring. Distinct D-dimer patterns may aid treatment guidance. Multicenter studies are needed to validate standardized pediatric protocols.