Efficacy and Safety of Thrombolysis for Pediatric Venous Thromboembolism: A Systematic Review and Meta-analysis Open Access

We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation versus anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in five population, intervention, comparison, outcomes (PICO) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals), and absolute effects per 1,000 patients. Certainty of evidence was assessed using GRADE. Thirteen non-randomized studies of intervention were included. No questions were addressed by randomized controlled trials. Thrombolysis might be associated with a higher major bleeding risk, clinically relevant non-major bleeding, or unspecified bleeding events with risk differences of 0.09 (-0.06, 0.23), 0.06 (-0.11, 0.22), and 0.09 (-0.04, 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in sub-massive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of post-thrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very low-certainty evidence due to confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE.