Factors associated with thrombotic complications after the fontan procedure: A secondary analysis of a multicenter, randomized trial of primary thromboprophylaxis for 2 years after the fontan procedure

Objectives: The study sought to identify factors associated with increased risk of thrombosis after Fontan. Background: The Fontan procedure is the culmination of staged palliation for patients with univentricular physiology. Thrombosis is an important complication after this procedure. Methods: An international multicenter randomized controlled trial of acetylsalicylic acid versus warfarin for thromboprophylaxis after the Fontan procedure was conducted in 111 patients, and did not show a significant difference regarding thrombotic complications. We performed a secondary analysis of this previously published manuscript to identify factors associated with thrombosis in this population. Standardized prospective data collection included independent adjudication of all events. Results: At 2.5 years after randomization, time-related freedom from thrombosis was 69% (all venous, no arterial events), with 28% of thrombosis presenting with clinical signs or events. Hazard of thrombosis was highest immediately after Fontan with a gradual increase in risk during late follow-up. In multivariable models, factors associated with higher risk of thrombosis were pulmonary atresia with intact ventricular septum (hazard ratio [HR]: 3.64, 95% confidence interval [CI]: 1.04 to 12.70, p = 0.04), pulmonary artery distortion (HR: 2.35, 95% CI: 0.96 to 5.73, p = 0.06), lower pre-operative unconjugated bilirubin (HR: 0.84 μmol/l, 95% CI: 0.72 to 0.99, p = 0.04), use of central venous lines for >10 days or until hospital discharge (HR: 17.8, 95% CI: 3.97 to 79.30, p < 0.001), and lower FiO₂ 24 h after the procedure (HR: 0.67/10%, 95% CI: 0.45 to 1.00, p = 0.06). Patients on warfarin who consistently achieved minimum target international normalized ratio levels or those on acetylsalicylic acid had a decrease in risk of thrombosis compared with patients who often failed to meet target international normalized ratio level (HR: 3.53, 95% CI: 1.35 to 9.20, p = 0.01). Conclusions: More favorable thromboprophylaxis strategies are needed in light of the difficulties in controlling warfarin therapy and the high prevalence of thrombosis in this population (International Multi Centre Randomized Clinical Trial of Anticoagulation in Children Following Fontan Procedures; NCT00182104)