High rate of recurrent venous thromboembolism in children and adolescents with unprovoked venous thromboembolism

J Thromb Haemost. 2023 Jan;21(1):47-56. doi: 10.1016/j.jtha.2022.11.031. Epub 2022 Dec 22.

Abstract

Background: Unprovoked venous thromboembolism (VTE) is rare in pediatrics. Current recommendations for anticoagulation duration after unprovoked VTE differ for pediatric and adult populations.

Objectives: This single-center, retrospective cohort study aimed to determine the incidence rate of recurrent VTE in children and adolescents with unprovoked VTE, evaluate the potential risk factors for recurrence, and describe the anticoagulation regimens and bleeding in this population.

Methods: Children with an index, unprovoked VTE at the age of 1 to <21 years between 2003 and 2021 were included. The time to recurrent VTE and anticoagulation duration were summarized using Kaplan-Meier estimators. Clinical covariates were assessed for association with recurrence using stratified Kaplan-Meier curves and univariate Cox proportional hazards regression.

Results: Eighty-five children met the inclusion criteria, and there were 26 recurrent events in 250 person-years of follow-up (incidence rate = 104 [95% CI, 71-153] per 1000 person-years). An age of ≥12 years at index VTE (hazard ratio [HR], 7.56; 95% CI, 1.60-35.83) and inherited thrombophilia (HR, 2.28; 95% CI, 1.05-4.95) were significantly associated with recurrent VTE. Female sex had a nonstatistically significant decreased hazard of recurrence (HR, 0.56; 95% CI, 0.25-1.27). Duration of anticoagulation was variable, with a median duration of 274 days (IQR, 101-2357) for outpatient therapeutic anticoagulation. Twelve of the 26 (46%) recurrent events occurred while anticoagulation was prescribed.

Conclusion: The incidence rate of recurrent VTE in pediatric patients with a prior unprovoked VTE is high, particularly for adolescents and those with inherited thrombophilia. Therefore, future research should focus on the efficacy of prolonged anticoagulation for this population.

Keywords: anticoagulants; pediatrics; recurrence; thrombosis; venous thromboembolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anticoagulants / therapeutic use
  • Blood Coagulation
  • Child
  • Female
  • Humans
  • Infant
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Thrombophilia* / complications
  • Thrombophilia* / diagnosis
  • Thrombophilia* / drug therapy
  • Venous Thromboembolism* / diagnosis
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / epidemiology

Substances

  • Anticoagulants

Supplementary concepts

  • Thrombophilia, hereditary