How I approach pharmacological thromboprophylaxis in children

The incidence of venous thromboembolism in children continues to rise, with the most recent analysis from the Pediatric Hospital Information Systems database in the United States reporting a 200-fold increase in pediatric hospitalization-related venous thromboembolism diagnoses over the past two decades. In the past decade, several pediatric venous thromboembolism risk prediction models have been published, in some cases derived from multi-institutional data and multicenter randomized clinical trials of thromboembolism prevention in specific pediatric subpopulations have been conducted. Yet, apart from children hospitalized for COVID-19, guidelines for thromboprophylaxis (TP) in children that address several distinct at-risk subpopulations and settings for venous thromboembolism are presently lacking. It is becoming increasingly apparent that approaches to pharmacological TP for hospitalized children should be risk-stratified regarding a priori risks of both venous thromboembolism and clinically-relevant bleeding. In this manuscript, we present model cases of common inpatient clinical scenarios and review the evidence related to venous thromboembolism risk models and pharmacological TP clinical trials in children, describing a pragmatic approach to pharmacological TP for each scenario. We then conclude by describing our evidence-informed, subpopulation- and setting-specific approach to pharmacological TP for the clinical scenarios and reviewing critical knowledge gaps well-suited for future pediatric trials to inform thromboprophylaxis in children.