Background There has been a significant increase in pediatric VTE over the last two decades, particularly among hospitalized children. Inherited and acquired thrombophilias have been previously associated with the development and recurrence of VTE in children; however, evidence is still lacking as to whether the presence of thrombophilia influences clinical outcomes in pediatric VTE. Current recommendations for thrombophilia testing are largely based on inconclusive data, and results rarely influence VTE management decisions.

Aims To describe the prevalence of inherited and acquired thrombophilias, as well as the characteristics and outcomes of VTE in a cohort of children presenting with VTE.

Methods We analyzed clinical and laboratory data from children (<21 years old) presenting with VTE who were enrolled in a single institutional-based prospective inception cohort study of pediatric VTE between May 2013 and July 2025. Demographic information, VTE characteristics and risk factors, family history, laboratory thrombophilia findings, treatment characteristics, and VTE outcomes were prospectively collected. Thrombophilia testing included factor V Leiden (FVL) and prothrombin (F2) gene mutations, protein C (PC), S (PS), and antithrombin (AT) deficiencies, antiphospholipid antibodies (aPLs), homocysteine, and lipoprotein a (Lp(a)). Testing was performed at the time of VTE presentation and, for those with positive results, confirmatory testing was repeated during the subacute/chronic post-VTE phase (≥6 weeks post-VTE). For children with positive aPLs at the time of diagnosis, repeat testing was performed at least 12 weeks apart. Descriptive statistics were used to summarize patient characteristics and outcomes.

Results A total of 177 children were included. The median age was 7 years, 53% were female, and 75% were white. The prevalence of at least one thrombophilia was 20% (n=36), while multiple thrombophilia traits were present in 6% of children (n=10). Among those diagnosed with thrombophilia, antiphospholipid syndrome (APS) and FVL mutations were the most common diagnoses (50% and 31%, respectively), while AT deficiency and F2 mutations were the least common (6% and 3%, respectively). No patient was diagnosed with PS deficiency.

Compared to children without thrombophilia, those with thrombophilia were older (median age 5.5 vs. 12.9 years, p=0.011), and more frequently female (49% vs. 69%, p=0.038). There were no significant differences in race or ethnicity. Children with thrombophilia had a higher frequency of pulmonary embolism (17% vs. 7%) and lower extremity deep venous thrombosis (DVT) (42% vs. 28%) compared to those without thrombophilia, who more commonly had upper extremity DVT (17% vs. 34%), but these differences were not statistically significant.

Children with thrombophilia had higher rates of unprovoked (31% vs. 8%, p<0.001) and drug-related VTE (28% vs. 12%, p=0.034), and lower rates of central venous catheter (CVC)-associated DVT (39% vs. 67%, p=0.004), compared to those without thrombophilia. Additionally, family history of early-onset VTE (11% vs. 6%) and obesity-related (17% vs. 8%) VTE were more common among children with thrombophilia compared to those without, but these differences were not statistically significant.

Children with thrombophilia had a higher rate of recurrent VTE compared to those without (28% vs. 11%, p=0.014). Rates of persistent thrombus occlusion, clinically relevant bleeding, post-thrombotic syndrome, and chronic pain were similar between the two groups.

Conclusions This single-center institutional cohort study of unselected children with VTE identified a thrombophilia prevalence of 20%. Children with thrombophilia were older, more frequently female, had a higher rate of unprovoked VTE and a lower rate of CVC-related VTE compared to those without thrombophilia. Rates of recurrent VTE were higher in children with thrombophilia compared to those without. Future multicenter cohort studies and registries are needed to better understand the impact of thrombophilia status on pediatric VTE outcomes.

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2025
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