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

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

Publication History

Received: 23 May 2024

Accepted: 20 December 2024

Accepted Manuscript online:
24 December 2024

Article published online:
16 January 2025

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