Safety and efficacy of fondaparinux in pediatric venous thromboembolism: A retrospective cohort study.

BACKGROUND: Pediatric venous thromboembolism (VTE) lacks robust, age-specific evidence to guide parenteral anticoagulation. Prior FondaKIDS studies suggested feasibility of fondaparinux but were limited by small samples, heterogeneous endpoints, and non-standardized assessments. OBJECTIVE: To assess long-term, real-world evidence on the safety, efficacy, and pharmacokinetics of fondaparinux in pediatric VTE using standardized dosing and harmonized outcome definitions. METHODS: This retrospective cohort study at Children's Hospital Los Angeles included patients <18 years receiving at least one dose of fondaparinux (n = 366). A weight-based dosing algorithm targeting anti-Xa 0.5-1.0 mg/L was applied. Endpoints were aligned with International Society on Thrombosis and Hemostasis (ISTH) pediatric standards, with imaging at Month 1 and Month 3 (±15 days) and "any time" analyses. Efficacy outcomes included clot resolution and recurrence. Safety outcomes included major bleeding, post-thrombotic syndrome (PTS), mortality, and adverse events of special interest. RESULTS: Therapeutic anti-Xa levels were achieved in 92.6% within a median of 3 days, with ~55% requiring no dose adjustment. At 3 months, complete resolution occurred in 44.9% (primary VTE) and 44.0% (all VTEs); 66.2% achieved complete or partial resolution. Overall, 75.1% achieved resolution at any time, consistent across subgroups. One-year VTE recurrence was ~8%. Major bleeding occurred in 1.9% (no fatalities); PTS in 1.6%. Mortality of 8.7% was driven by comorbidities. CONCLUSIONS: This largest pediatric fondaparinux cohort demonstrates rapid therapeutic anticoagulation, clinically meaningful clot resolution, and low bleeding risk using standardized dosing and ISTH-harmonized endpoints, supporting its role as a once-daily parenteral option when DOACs are unsuitable and informing pediatric labeling.