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<p>The Fontan procedure, the standard palliation for single-ventricle congenital heart disease, is associated with a high burden of thromboembolic complications of unclear etiology. We investigated whether increased circulating lipopolysaccharide (LPS) related to a compromised intestinal barrier is involved in thromboembolic manifestations and markers in the Fontan population. We examined 48 stable adults with Fontan circulation (median age 23 years; range 18–40) and 31 age-matched controls. We assessed serum LPS, and zonulin (marker of increased gut permeability), along with coagulation factors (F; prothrombin, FV, FVII-FX), thrombin generation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes), endogenous anticoagulants (antithrombin, free protein S, tissue factor pathway inhibitor), markers of fibrinolysis (α2-antiplasmin, clot lysis time, plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor), platelet activation (P-selectin, sCD40L), and endothelial injury (von Willebrand factor (vWF), thrombomodulin). Compared with controls, patients with Fontan circulation exhibited higher LPS (+ 207%) and zonulin (+ 125%), which were strongly correlated (<i>r</i> = 0.63; <i>P</i> &lt; 0.001). In the Fontan group, LPS was positively associated with vWF (<i>r</i> = 0.76; <i>P</i> &lt; 0.001), and inversely with free protein S (<i>r</i> = − 0.30; <i>P</i> = 0.04), but not with any other markers. Ten patients (21%) with prior thromboembolic events had higher adjusted (age, sex, BMI) LPS (+ 198%; <i>P</i> &lt; 0.001) and zonulin (+ 147%; <i>P</i> &lt; 0.001) compared with remainder, accompanied by higher vWF (+ 119%), P-selectin (+ 137%), sCD40L (+ 139%), as well as lower FVIII (− 20%) and protein S (− 22%). We are the first to report that patients with Fontan circulation exhibit higher LPS levels related to increased intestinal permeability, which may predispose to thromboembolism and have practical implications.</p> Graphical abstract <p></p>

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Low-grade endotoxemia as an additional prothrombotic mechanism in adults with Fontan circulation

  • 期刊论文

  • 发表日期：

    2026年4月6日

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  • Paweł Skorek,
  • Lidia Tomkiewicz-Pająk,
  • Agnieszka Bartczak-Rutkowska,
  • Mirosław Kowalski,
  • Anetta Undas

摘要

The Fontan procedure, the standard palliation for single-ventricle congenital heart disease, is associated with a high burden of thromboembolic complications of unclear etiology. We investigated whether increased circulating lipopolysaccharide (LPS) related to a compromised intestinal barrier is involved in thromboembolic manifestations and markers in the Fontan population. We examined 48 stable adults with Fontan circulation (median age 23 years; range 18–40) and 31 age-matched controls. We assessed serum LPS, and zonulin (marker of increased gut permeability), along with coagulation factors (F; prothrombin, FV, FVII-FX), thrombin generation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes), endogenous anticoagulants (antithrombin, free protein S, tissue factor pathway inhibitor), markers of fibrinolysis (α2-antiplasmin, clot lysis time, plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor), platelet activation (P-selectin, sCD40L), and endothelial injury (von Willebrand factor (vWF), thrombomodulin). Compared with controls, patients with Fontan circulation exhibited higher LPS (+ 207%) and zonulin (+ 125%), which were strongly correlated (r = 0.63; P < 0.001). In the Fontan group, LPS was positively associated with vWF (r = 0.76; P < 0.001), and inversely with free protein S (r = − 0.30; P = 0.04), but not with any other markers. Ten patients (21%) with prior thromboembolic events had higher adjusted (age, sex, BMI) LPS (+ 198%; P < 0.001) and zonulin (+ 147%; P < 0.001) compared with remainder, accompanied by higher vWF (+ 119%), P-selectin (+ 137%), sCD40L (+ 139%), as well as lower FVIII (− 20%) and protein S (− 22%). We are the first to report that patients with Fontan circulation exhibit higher LPS levels related to increased intestinal permeability, which may predispose to thromboembolism and have practical implications.

Graphical abstract