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.