Real-World Anticoagulant Use and Incidence of Venous Thromboembolism and Major Bleeding in Children

Clin Ther. 2021 Dec;43(12):2074-2087. doi: 10.1016/j.clinthera.2021.09.021. Epub 2021 Dec 3.


Purpose: Children generally have a lower risk of venous thromboembolism (VTE) than adults, but those with acute and chronic conditions requiring hospitalization and surgical procedures are at increased risk. Anticoagulant use in children has not been systematically studied, and limited data exist. This study aimed to provide data on the conditions associated with use of anticoagulants, the type of anticoagulant used in children, and the incidence of thromboembolism and major bleeding events reported in this population.

Methods: To increase understanding of the use of anticoagulant therapies in children with at-risk conditions, 3 health claims databases in the United States were analyzed to describe the characteristics of use of heparins, warfarin, and direct oral anticoagulants (DOACs). Cumulative drug exposure was determined for continuous exposure, defined as >30 days. Unadjusted event rates of VTE and major bleeding after exposure to these therapies were reported. The data were presented descriptively and are not intended for comparison or to imply any causation.

Findings: Anticoagulants were infrequently used in the pediatric population, including at any time point after Fontan surgery for congenital heart disease. Heparins were used most frequently in the population overall and especially for patients aged <12 years. DOACs were used least often and primarily for patients ages 12 to <18 years. Among pediatric patients exposed to anticoagulants, unadjusted incidence rates of VTE per 1000 person-years of exposure ranged from 30.8 to 34.0 for all DOACs, 21.6 to 46.2 for warfarin, and 6.0 to 7.3 for heparins. Rates per 1000 person-years for major bleeding ranged from 0 to 4.9 for all DOACs, 4.3 to 6.7 for warfarin, and 3.7 to 4.6 for heparins.

Implications: With results from clinical trials evaluating DOACs in the pediatric population expected in the next 2 years, these descriptive real-world data may provide a baseline understanding of current prescribing patterns and outcomes associated with the use of DOACs and other anticoagulants in routine pediatric clinical practice. This information represents the use of real-world evidence and may function as the benchmark for evaluating changes in prescription practices and potential outcomes in the future.

Keywords: Anticoagulant; bleeding; children; real-world; venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Anticoagulants / adverse effects
  • Child
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Risk Factors
  • Venous Thromboembolism* / chemically induced
  • Venous Thromboembolism* / drug therapy
  • Venous Thromboembolism* / epidemiology


  • Anticoagulants