Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients

Background Fontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains unclear. Objective To correlate liver dysfunction and haemostatic profiles with clinical outcomes in the Fontan population. Patients/methods Patients were enrolled in a multicentre, cross-sectional study in Australia and New Zealand. Hepatic structure and function were assessed using serum-based calculations (Fibrotest and model for end-stage liver disease excluding international normalised ratio scores). Haemostatic profiles were assessed by Thrombin Generation. Platelet function was assessed via Platelet Factor 4 (PF4) and P-selectin (P-SEL). Clinical outcomes were obtained from the Australian and New Zealand Fontan Registry. Results Seventy-three patients participated in the study (mean age 18.9 +/- 8.5 years with a mean of 13.5 +/- 6.9 years post-Fontan). The Endogenous Thrombin Potential (ETP) for patients who suffered thrombotic events (TE) (1366.4 +/- 66.2 nM/min) was higher compared with patients with major bleeding events (1011.1 +/- 138.4 nM/min) (p=0.03). Except for a negative correlation between Fibrotest-score and PF4 (p=0.045), PF4 and P-SEL concentrations did not correlate with markers of hepatic dysfunction or structural abnormality. Conclusions Increased ETP is associated with TE during clinical follow-up after Fontan. This study reinforces that hepatic dysfunction may contribute to the derangement of coagulation factors, impacting the individual risk of haemostatic complications for the Fontan population.