Recurrence Rate and Hazard Modeling for Recurrence in Children with a First Episode of Venous Thromboembolism

Pediatric venous thromboembolism (VTE), although rare, is associated with significant morbidity and mortality. A more thorough understanding of the epidemiology of pediatric VTE is needed to advance the field. Published recurrence rates in this age group vary widely, ranging from 5.5% to 18.5%, and currently studies assessing contributing risk factors for recurrence are sparse.

To describe the recurrence rate of venous thromboembolism after a first time episode of VTE in a provincial cohort of children aged 0–17 (inclusive) and determine predictors of recurrence after incident VTE.

A retrospective cohort of children (ages 0–17 inclusive) with a first time diagnosis of VTE in the province of Quebec over an eleven-year period was obtained from a comprehensive administrative hospital database (Med-Echo). The study period began on January 1^st, 1994 and ended on December 31^st, 2004 for inclusion of incident cases. Subjects were followed from the time of their admission into the cohort (at time of incident VTE), until their first recurrence, death, emigration from the province or end of the study period (December 31^st, 2005), whichever came first. The following demographic and risk factor information were extracted for the cohort: age, age category, sex, type of VTE at initial presentation, prior major surgery, prior major infection, prior congenital heart disease, prior central line, prior trauma, cancer or recent bone marrow transplantation, and diagnosis of a chronic disease. Chronic diseases extracted included systemic lupus erythematosus, inflammatory bowel disease, cystic fibrosis, nephrotic syndrome and sickle cell disease. Recurrence rates were then calculated and univariate Cox-proportional hazard model and log rank testing were used to assess which risk factors would be incorporated into the final multivariate Cox-proportional hazard model evaluating risk of VTE recurrence.

In total, 518 incident cases of VTE in children 0–17 years of age were documented. Median follow up time in cohort was 4.4 years (range 1 day – 12 years). Overall the cohort had a recurrence rate of 2.77 per 1000 person-months (95% confidence interval (CI) 2.2–3.4) (recurrence risk of 16%). Multivariate Cox proportional hazard modeling showed a statistically significant increased risk of recurrence with the presence of a chronic disease (HR 2.40; 95% CI 1.26–4.56) and a diagnosis of portal vein thrombosis as the initial VTE presentation (HR 3.29; 95% CI 1.30–8.34). Overall all-cause mortality was 6.4% with 33 deaths in the cohort.

The risk of recurrence is comparable to those prior studies that had shown higher recurrence risks. The rate of VTE recurrence is higher in those with a pre-existing chronic illness or with an initial diagnosis of portal vein thrombosis. Overall all-cause mortality was lower in our cohort than prior large studies of VTE in this age group. Our findings highlight the need for future studies to determine effective secondary prophylaxis strategies in children at high risk for VTE recurrence.

No relevant conflicts of interest to declare.