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Thromb Haemost
DOI: 10.1055/a-2507-2449
Coagulation and Fibrinolysis

Activation of the Contact System and Intrinsic Pathway in Peripheral and Portal Venous Circulations in Liver Cirrhosis

Elena Campello 
1   Internal Medicine 1, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
,
Alberto Zanetto
2   Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
,
Yuriy Prokopenko
3   Division of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, United States
,
Anton Ilich
3   Division of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, United States
,
Chatphatai Moonla
3   Division of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, United States
,
Cristiana Bulato
1   Internal Medicine 1, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
,
Serena Toffanin
1   Internal Medicine 1, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
,
Sarah Shalaby
2   Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
,
Romilda Cardin
2   Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
,
Giulio Barbiero
4   Radiology Unit, Department of Medicine, Padova University Hospital, Padova, Italy
,
Sabrina Gavasso
1   Internal Medicine 1, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
,
Nigel S. Key
3   Division of Hematology and Blood Research Center, Department of Medicine, University of North Carolina, Chapel Hill, United States
,
Marco Senzolo
2   Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
,
Paolo Simioni
1   Internal Medicine 1, Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy
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Abstract

Background Portal vein system-specific risk factors contributing to portal vein thrombosis in cirrhosis are poorly investigated.

Aim This study aimed to quantify contact system and intrinsic pathway activation in the 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:C1-INH [plasma kallikrein:C1-esterase inhibitor] and FXIIa:C1-INH) and intrinsic pathway activation (FXIa:C1-INH, FXIa:α1at [α-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. The etiology 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.

Conclusion Markers of contact system and intrinsic pathway activation in the systemic circulation were significantly higher in cirrhosis versus controls. Complexes of FXIa and FIXa with AT were significantly higher in the portal than in peripheral plasma in cirrhosis, possibly indicating a unique heparin-like effect in portal venous blood.

Keywords

acquired coagulopathy - antithrombin - coagulation - endothelial injury - portal vein thrombosis

Supplementary Material



Publikationsverlauf

Eingereicht: 23. Mai 2024

Angenommen: 20. Dezember 2024

Accepted Manuscript online:
24. Dezember 2024

Artikel online veröffentlicht:
16. Januar 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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