Author + information
- Received May 10, 2012
- Revision received July 24, 2012
- Accepted August 13, 2012
- Published online January 22, 2013.
- Brian W. McCrindle, MD, MPH⁎,⁎ (, )
- Cedric Manlhiot, BSc⁎,
- Andrew Cochrane, MD†,
- Robin Roberts, MSc‡,
- Marina Hughes, DPhil†,
- Barbara Szechtman, BA‡,
- Robert Weintraub, MBBS†,
- Maureen Andrew, MD⁎,
- Paul Monagle, MD, MSc, MBBS†,
- Fontan Anticoagulation Study Group
- ↵⁎Reprint requests and correspondence:
Dr. Brian W. McCrindle, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada
A version of this paper was presented at the 2008 Scientific Sessions of the American Heart Association, November 8 to 12, 2008, New Orleans, Louisiana.
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)
This work was supported by a research grant from the Heart and Stroke Foundation of Ontario (grant-in-aid NA-3565), National Heart Foundation of Australia project grant, the Henderson Research Centre, Hamilton, and the CIBC World Markets Children’s Miracle Foundation. Mr. Roberts is a statistical consultant for Coaxia Inc. and Bayer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Andrew is now deceased.
- Received May 10, 2012.
- Revision received July 24, 2012.
- Accepted August 13, 2012.
- American College of Cardiology Foundation