Venous thromboembolism (VTE), a condition involving the formation of blood clots in deep veins that may lead to serious complications like pulmonary embolism, remains a significant clinical concern in children, particularly those with underlying conditions such as congenital heart disease or cancer. While acute treatment of pediatric VTE has improved over the years, there has been a lack of data regarding the safety and efficacy of extended anticoagulant therapy in children until now.
A recent long-term study published in The Lancet Haematology, led by an international team spearheaded by Christoph Male at MedUni Vienna, has addressed this gap by evaluating extended-phase anticoagulation in children who previously participated in the EINSTEIN-Jr trial. This earlier randomized controlled study had already demonstrated that rivaroxaban, a direct oral anticoagulant, was as effective and safe as standard therapies like heparin or vitamin K antagonists in treating pediatric VTE during the acute phase.
The new study followed 248 children aged 17 years or younger who completed the initial 1–3-month acute treatment period and were eligible for extended anticoagulation for up to nine months (or two months for children under two years with catheter-related VTE). Of these, 214 children received bodyweight-adjusted rivaroxaban or standard anticoagulants within the framework of the study, while 34 received extended treatment outside the trial protocol.
During the extended treatment phase, only three children (1%) experienced a recurrent VTE, corresponding to a cumulative incidence of 3.0%. Clinically relevant non-major bleeding occurred in four children (2%), with a cumulative incidence of 3.3%. Importantly, there were no cases of fatal VTE or major bleeding, and outcome rates were comparable between rivaroxaban and standard anticoagulants.
The study also explored factors influencing the decision to continue anticoagulation. Children with symptomatic initial VTE, unprovoked VTE or persistent risk factors, and those showing residual thrombosis on repeat imaging were more likely to receive extended treatment. These findings offer important clinical guidance, suggesting that the decision to prolong anticoagulation is driven by identifiable risk factors for recurrence.
This long-term data underscores the safety and efficacy of rivaroxaban for extended use in children and supports its role as an age-appropriate alternative to traditional anticoagulants. Unlike older therapies that require injections and frequent blood tests, rivaroxaban offers the practical benefits of oral administration and minimal monitoring, which is especially advantageous in pediatric care.
Rivaroxaban, an oral anticoagulant, exerts its therapeutic effect by directly inhibiting Factor Xa—both free and prothrombinase-bound—as well as Factor Xa within the prothrombinase complex. This inhibition disrupts the coagulation cascade, reducing thrombin generation and preventing fibrin clot formation. Unlike heparin, it does not require antithrombin as a cofactor. Since its initial FDA approval in 2011 for DVT prevention in adults undergoing orthopedic surgery, its indications have expanded to include treatment and secondary prevention of DVT and pulmonary embolism, stroke prevention in patients with nonvalvular atrial fibrillation, and reduction of cardiovascular events in patients with coronary artery disease or peripheral artery disease. In 2021, it was also approved for use in children for the treatment and prevention of VTE.
With these new results, rivaroxaban emerges as the first scientifically validated option for both short- and long-term anticoagulation in children. Its oral administration and minimal need for monitoring offer practical advantages over traditional therapies, making it particularly well-suited for pediatric care. The consistent safety and efficacy observed between the acute and extended phases in children align with trends seen in adult studies, providing additional reassurance for clinicians. These findings could significantly influence future treatment strategies and support the standardization of long-term anticoagulation practices in pediatric thrombosis management.
References
- Male C, Lensing AWA, Chan AKC, Kenet G, Young G, Bhat R, et al. Extended-phase anticoagulant treatment of acute venous thromboembolism in children: a cohort study from the EINSTEIN-Jr phase 3 trial. The Lancet Haematology. 2025 May 1;12(5):e357–64.
- Mitchell L, Rodriguez V. Lessons from EINSTEIN-Jr and next steps for extended-phase anticoagulation in paediatric venous thromboembolism. The Lancet Haematology. 2025 May 1;12(5):e321–3.