Venous thromboembolism (VTE) is no longer a rare complication in pediatric inpatients and is emerging as a clinically relevant condition with an impact on health care delivery and organization. Far from being an isolated phenomenon, the literature shows an increase in its incidence over the past few decades. A multicenter study in children’s hospitals across the United States confirmed that the venous thromboembolism (VTE) admission rate rose from 46 cases per 10 000 admissions in 2008 to 106 per 10 000 in 2019, corresponding to a 130% increase from 2008 to 2019 and a 211% increase since 2001.1

This increase cannot be attributed solely to improved diagnostic sensitivity or the widespread use of imaging techniques. It likely reflects structural changes in contemporary pediatric medicine: improved survival rates among children with complex diseases, an increase in chronic conditions, technology dependence, and more frequent use of central venous catheters. In this context, VTE is emerging as a paradigmatic complication of modern medicine, primarily affecting critically ill children who are admitted to intensive care units (ICUs), undergoing surgical procedures, or suffering from multiple comorbidities.1

The clinical relevance of pediatric VTE lies in the fact that it is neither an incidental finding nor a minor complication. It is currently considered the second leading cause of iatrogenic harm in hospitalized children, following catheter-related infection. It can have serious repercussions, including pulmonary embolism, paradoxical embolism, stroke, loss of venous access, infection, pain, and increased hospital cost and length of stay. In addition, there may be long-term complications, such as post-thrombotic syndrome, resulting in functional impairment and decreased quality of life. From this point of view, the prevention and proper management of VTE should be considered a strategic objective in health planning and patient safety policies.

Despite its growing impact, the evidence supporting the management of pediatric VTE remains limited. For years, many pediatric guidelines and recommendations have been based on studies conducted in adults, uncritically extrapolating their conclusions to a population that has particular pathophysiological characteristics. Children cannot be viewed simply as a smaller version of adults; pediatric thrombosis has specific characteristics in terms of its etiology, clinical presentation, and recommended diagnostic and therapeutic management.2

In children, VTE tends to be secondary to acquired factors, whereas in adults it is predominantly associated with atherosclerosis, chronic comorbidities, and persistent prothrombotic states. In the pediatric population, the main risk factor is the presence of a central venous catheter, especially in newborns and critically ill patients. Other risk factors include hospitalization, infection, surgery, immobilization, and diseases such as cancer, congenital heart disease, or short bowel syndrome. A key distinguishing factor is age-related variation. Newborns have an immature hemostatic system, with physiological variations in coagulation factors, endogenous anticoagulants, and fibrinolysis, which affect both the risk of thrombosis and the interpretation of diagnostic tests. In adolescents, hormonal changes, obesity, sedentary lifestyle habits, and (in adolescent girls) the use of estrogen play a greater role.

These differences translate directly to the management of VTE. In pediatric patients, especially in newborns, developmental hemostasis significantly influences the response to anticoagulants. The physiologically lower concentrations of antithrombin, protein C, and protein S, along with variations in vitamin K-dependent factors, explain why the same drug can produce different effects depending on age. Thus, newborns and infants may exhibit an apparent “resistance” to heparins, since their effect depends on endogenous antithrombin, and the maturation of clotting factors is not complete in the early months of life.2

In this context, direct oral anticoagulants (DOACs) represent the most significant change in the treatment of pediatric VTE over the past decade. These drugs offer a long-awaited option for children and adolescents: effective oral anticoagulation with more predictable pharmacokinetics and without the burden of daily subcutaneous injections, venous access, or close laboratory monitoring. In pediatric patients, these factors have a particularly significant impact on treatment adherence, quality of life, and how the family experiences the treatment.3

The available evidence can no longer be considered preliminary. Clinical trials have demonstrated the noninferiority of rivaroxaban and dabigatran as alternatives to conventional treatment for acute VTE in children following an initial phase of parenteral anticoagulation, with low recurrence rates and no significant increase in bleeding. In addition, their indications have been expanded beyond the treatment of VTE, particularly for thromboprophylaxis in congenital heart disease, for instance, in the context of Fontan surgery, where rivaroxaban has proven useful.3 This new era in pediatric anticoagulation, which is finally founded on evidence specific to this population, has been reinforced by the recent publication of the joint guidelines from the American Society of Hematology (ASH) and the International Society on Thrombosis and Haemostasis (ISTH) in May 2025, which recommend the use of DOACs over standard-of-care anticoagulation in many pediatric VTE scenarios2.

However, enthusiasm must be tempered by caution. The trial samples do not fully represent the actual epidemiology of pediatric thrombosis. Patients with catheter-related thrombosis, very young infants, newborns, critically ill patients, and patients with complex comorbidities have been underrepresented. Furthermore, relevant questions remain regarding the role of DOACs in conditions such as antiphospholipid syndrome, cancer, arterial thrombosis, perioperative management, or menstrual bleeding, monitoring in special situations, and pharmacological reversal.

In Spain, rivaroxaban and dabigatran are approved for the treatment and secondary prevention of VTE in pediatric patients. However, public funding for DOACs is still limited to the adult population, primarily for nonvalvular atrial fibrillation and prophylaxis following major orthopedic surgery. The lack of funding for pediatric indications constitutes a significant barrier to their use and poses an additional problem for families with socioeconomic vulnerability, and it is a source of inequity in the access to evidence-based treatments.

Finally, thromboprophylaxis in pediatrics has ceased to be a secondary consideration to become a clinical and patient-safety priority. Venous thromboembolism is now the second most frequent hospital-acquired condition in children. However, in contrast to the adult population, prevention efforts continue to be guided by incomplete evidence, with no universal guidelines, and rely heavily on individual risk stratification.4 The main developments in this area stem from studies focused on specific subgroups (critically ill patients, cancer patients, patients with heart disease, or patients with central venous catheters) involving different heparin regimens as well as the emerging use of DOACs.5

In summary, in pediatric inpatients, thrombosis should be interpreted as an indicator of medical complexity and potentially preventable harm, and it evinces the urgent need for specific strategies for risk stratification, active surveillance, and prevention. Its management requires specific protocols, a multidisciplinary approach, and individualized anticoagulation that takes into account the patient’s age, risk factors, and comorbidities. This is the only way to move toward safer, more equitable, and evidence-based care in the pediatric population.