Background and Aims Venous malformations (VMs) are the most prevalent subtype of congenital vascular malformations and may be complicated by localized intravascular coagulopathy or acute venous thrombosis, frequently leading to pain, edema, and functional limitations. Standard anticoagulation for these events typically involves low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs), which pose challenges in the pediatric population due to subcutaneous administration, need for monitoring, and dietary restrictions.

Rivaroxaban, an oral direct factor Xa inhibitor, has shown safety and efficacy in pediatric patients with venous thromboembolism in recent trials (e.g., EINSTEIN-Jr), and its use in the context of vascular malformations remains underreported. We present updated data from our institutional experience on the use of rivaroxaban in pediatric patients with VMs complicated by thrombosis, focusing on symptomatic improvement and safety.

Methods This is a retrospective, observational study conducted at Bambino Gesù Children's Hospital. We included patients under 18 years of age with confirmed venous malformations complicated by thrombosis, treated with rivaroxaban between September 2022 and April 2025. Patients received rivaroxaban either following acute anticoagulation (≥5 days of LMWH) or as secondary prophylaxis after a prior thrombotic event. Data on demographics, clinical presentation, radiologic findings, thrombophilia screening, treatment duration, and follow-up were collected. Primary outcomes were symptomatic improvement (primarily pain) and safety profile. Secondary outcomes included recurrence and radiological evolution of thrombosis.

Results A total of 60 patients were included, with a median age of 13.4 years. Rivaroxaban was initiated for treatment of acute thrombosis in 54 patients (90%) after at least 5 days of LMWH, and for secondary prophylaxis in 6 (10%) with a history of prior thrombotic events.

At the time of analysis, all patients had completed at least 3 months of follow-up. Pain and functional impairment, the predominant clinical symptoms, improved significantly in the entire cohort: 85% (n=51) reported complete resolution within the first 3 months, while the remaining 15% (n=9) experienced partial improvement. None reported worsening symptoms. No thrombotic recurrences were documented during follow-up.

A subset of patients received rivaroxaban for more than one year, with sustained improvement in pain and functional impairment and no thrombotic recurrence.

Treatment was well tolerated in the vast majority. No major or clinically relevant non-major bleeding events were reported. One patient discontinued treatment after 6 months due to alopecia. Minor gastrointestinal discomfort (nausea or abdominal pain) occurred in 3 patients and resolved spontaneously or with temporary dose adjustment.

Menorrhagia was reported in three female patients during the first months of treatment; in these cases, a temporary dose reduction was implemented with good clinical response.

Radiologic follow-up is ongoing. Among the patients with available imaging at 6 or 12 months (n=40), 45% showed complete recanalization, 35% had partial resolution or improved flow, and 20% showed stable findings without progression. No new thrombi were identified during treatment.

Thrombophilia screening was performed in the majority of patients; the data is currently under analysis to determine clinical relevance.

Conclusions Our updated experience suggests that rivaroxaban is a safe and well-tolerated alternative to standard anticoagulation in pediatric patients with venous malformations complicated by thrombosis. In addition to its favorable safety profile, oral administration and lack of monitoring requirements make rivaroxaban a practical option in this population. Further prospective studies are needed to validate its efficacy in symptom control and thrombosis resolution in this unique patient group.

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2025
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