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.