In silico thrombin and factor Xa generation profiles in adult patients after Fontan operation.

Abstract

: Single-ventricle defects are associated with increased risk of thromboembolic events. To analyze the prothrombotic potential in a long-term follow-up on Fontan patients via plasma contribution to thrombin and factor (F)Xa generation profiles. Thrombin and FXa generation was simulated from plasma concentrations of FII, FV, FVII, FVIII, FIX, FX, antithrombin and tissue factor (TF) pathway inhibitor from Fontan patients (n = 48) and healthy controls (n = 34). TF and thrombin-antithrombin complex (TAT) were measured by ELISA. Fontan patients had significantly reduced procoagulant protein concentrations and increased anticoagulant protein concentrations over controls, resulting in a lowered procoagulant potential. However, Fontan patients showed increased hemostatic activation as evidenced by increased TF and TAT. Modeling this increased TF showed a more prothrombotic profile. Observed changes in procoagulant and anticoagulant proteins may be a compensatory mechanism aimed at mitigating the underlying disease effects characterized by elevated TF and TAT.