Thromboembolic complications in Fontan patients: population-based prevalence and exploration of the etiology

After the Fontan procedure, patients face an increased risk for thromboembolic events (TE). The etiology for this increased thrombogenecity is incompletely understood. This study aimed to determine the prevalence of TE in Danish Fontan patients and to bring new insights into the etiology of TE. Using a population-based design, we retrospectively identified all TEs in 210 Fontan patients. Whole blood assays (thromboelastography, thromboelastography functional fibrinogen and Multiplate) reflecting global hemostasis, clot strength and platelet aggregation were analyzed prospectively in 112 patients and plasma was analyzed in 76 patients for biomarkers reflecting endothelial-, glycocalyx-, platelet-, and fibrinolysis function (histone-complexed DNA fragments, Protein C, soluble CD40 ligand, soluble thrombomodulin, syndecan-1, tissue-type plasminogen activator). The results were compared in groups stratified according to age, antithrombotic therapy, TE, and glycocalyx degradation (syndecan-1 < or ≥ median). Correlation between biomarkers and demographic-, anatomical-, clinical- and biochemical parameters was investigated. The prevalence of TE was 8.1 % after a mean follow-up of 8.4 years. None of the stratified groups demonstrated evidence of hypercoagulability in the whole blood assays and no unexpected significant differences were found between the groups. All biomarkers, except protein C, correlated with one another and after stratification of glycocalyx degradation only syndecan-1 levels ≥ median correlated with other biomarkers. The prevalence of TEs was 8.1 % after mean follow-up of 8.4 years. Overall, the hemostatic profile appeared normal, however, in a subset of patients, evidence of some endothelial activation/damage including glycocalyx degradation and fibrinolysis was found, identifying a potentially more thrombogenic group.