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Thromb Haemost
DOI: 10.1055/a-2507-2449
Original Article

Activation of the contact system and intrinsic pathway in peripheral and portal venous circulations in liver cirrhosis

Elena Campello 
1   Department of Medicine, General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Padua, Italy
,
Alberto ZAnetto
2   University of Padova, Padova, Italy
,
Yuriy Prokopenko
3   The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States (Ringgold ID: RIN6797)
,
Anton Ilich
3   The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States (Ringgold ID: RIN6797)
,
Chatphatai Moonla
3   The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, United States (Ringgold ID: RIN6797)
,
Cristiana Bulato
4   Department od Cardiologic, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
,
Serena Toffanin
1   Department of Medicine, General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Padua, Italy
,
Sarah Shalaby
5   Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Multivisceral Transplant Unit, Padua, Italy
,
Romilda Cardin
5   Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Multivisceral Transplant Unit, Padua, Italy
,
Giulio Barbiero
2   University of Padova, Padova, Italy
,
Sabrina Gavasso
6   University of Padua, Padua, Italy
,
Nigel S Key
7   University of North Carolina School of Medicine, Chapel Hill, Chapel Hill, United States
,
Marco Senzolo
2   University of Padova, Padova, Italy
,
Paolo Simioni
8   Dep of Cardiological, Thoracic and Vascular Sciences, University of Padua ; 2nd Chair of Internal Medicine, Padua, Italy
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Background: Portal vein system-specific risk factors contributing to portal vein thrombosis in cirrhosis are poorly investigated. Aims: To quantify contact system and intrinsic pathway activation in peripheral compared to portal venous blood in patients with decompensated cirrhosis. Methods: Adult patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt underwent simultaneous blood sampling from a peripheral vein and the portal vein. Complexes of serine proteases with their respective inhibitors were measured by ELISA to quantify contact system (PKa:C1INH [kallikrein:C1-esterase inhibitor] and FXIIa:C1INH) and intrinsic pathway activation (FXIa:C1INH, FXIa:α1at [alpha-1 antitrypsin], FXIa:AT [antithrombin], and FIXa:AT). Results: Twenty patients with cirrhosis (mean age 55 ± 7 years, M=58%, Child-Pugh A/B/C 6/11/3) and 25 healthy controls (mean age 45 ± 12 years, M=60%) were enrolled. Aetiology of cirrhosis was primarily alcohol abuse, followed by chronic viral infection. Log-transformed peripheral levels of all the complexes were significantly higher in patients compared with controls. While levels of PKa:C1 INH, FXIIa:C1 INH, FXIa:C1 INH and FXIa:α1at were similar in peripheral and portal venous blood in cirrhotic patients, FXIa:AT and FIXa:AT levels were significantly higher in portal blood (p = 0.013 and 0.011, respectively). FXIa:C1 INH significantly correlated with both contact system complexes (FXIIa:C1 INH and PKa:C1 INH) and with FIX:AT. Conclusions: Markers of contact system and intrinsic pathway activation in the systemic circulation were significantly higher in cirrhosis vs. controls. Complexes of FXIa and FIXa with AT were significantly higher in the portal than in peripheral plasma in cirrhosis, possibly indicating unique heparin-like effect in portal venous blood.



Publication History

Received: 23 May 2024

Accepted after revision: 20 December 2024

Accepted Manuscript online:
24 December 2024

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