title: 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.
abstract: OBJECTIVE
  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 FiO(2) 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.
authors.affiliation: Labatt Family Heart Centre, Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. brian.mccrindle@sickkids.ca
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.forename: Andrew
authors.initials: A
authors.lastname: Cochrane
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.forename: Marina
authors.initials: M
authors.lastname: Hughes
authors.forename: Barbara
authors.initials: B
authors.lastname: Szechtman
authors.forename: Robert
authors.initials: R
authors.lastname: Weintraub
authors.forename: Maureen
authors.initials: M
authors.lastname: Andrew
authors.forename: Paul
authors.initials: P
authors.lastname: Monagle
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects*; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control; D013927:Thrombosis / Q000517:prevention & control*; D018785:Tricuspid Atresia / Q000601:surgery; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin