Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial

Abstract

Objectives: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. Design: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. Setting: Seven PICUs. Patients: Children less than 18 years old with newly inserted central venous catheter. Interventions: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2–0.5 international units/mL versus usual care. Measurements and Main Results: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37–2.44) in infants and 0.24 (95% credible interval, 0.04–0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78–437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7–74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 10³/mm³ (interquartile range, 17–61 × 10³/mm³). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. Conclusions: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.