PB1343 - Systemic and portal venous contact and intrinsic pathway activation in liver cirrhosis

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Elena Campello, PhD

Assistant Professor
General Internal Medicine Unit and Thrombotic and Hemorrhagic Disease Unit, Department of Medicine, Padova University Hospital, Padova, Italy
Padova, Veneto, Italy

Co-Author(s)

AZ

Alberto Zanetto

Researcher
Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
Padova, Veneto, Italy
AI

Anton Ilich

Postdoctoral Research Associate
UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
YP

Yuriy Prokopenko

Postdoctoral Research Associate
UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
NK

Nigel S. Key

Professor
Division of Hematology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
MS

Marco Senzolo

MD
Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
Padova, Veneto, Italy
Paolo Simioni, MD, PhD

Head of Department of Medicine
University of Padova, Padova University Hospital
Padova, Veneto, Italy

Background: Portal vein thrombosis (PVT) is the most common thrombotic complication in cirrhosis; however, local risk factors involved in its pathogenesis are still not well understood.

Aims: To quantify contact and intrinsic pathway activation in peripheral and portal vein plasma in patients with cirrhosis and portal hypertension.

Methods: Adult patients with liver cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) underwent blood sampling from a peripheral vein and the portal vein the same day. Complexes of proteases with their respective inhibitors were measured by ELISA to quantify contact system (PKa:C1 [kallikrein:C1-esterase inhibitor] and FXIIa:C1) and intrinsic pathway activation (FXIa:C1, FXIa:α1at [alpha-1 antitrypsin], FXIa:AT [antithrombin], and FIXa:AT). Complex levels were compared with peripheral blood levels in healthy controls. Additionally, peripheral complex levels were compared with portal vein levels and potential association of patient- and cirrhosis-specific characteristics with complex levels were evaluated.

Results: Twenty patients with cirrhosis (mean age 55 ± 7 years, M=58%) and 25 healthy controls (45 ± 12 years, M=60%) were enrolled. Indications for TIPS were refractory ascites (n = 12), secondary prophylaxis for recurrent variceal bleeding (n = 8). Log-transformed peripheral levels of all complexes were significantly higher in patients compared with controls. Interestingly, levels of FXIa:AT and FIXa:AT were significantly higher in portal than peripheral plasma (p 0.013 and 0.0011, respectively). PKa:C1, FXIIa:C1, FXIa:C1 and FXIa:α1at were similar in peripheral and portal venous blood (Figure 1). FXIa:C1 complexes correlated with FXIIa:C1 and PKa:C1 and with FIX:AT complexes (Figure 2). FXIa complexes (FXIa:C1, FXIa:AT, and FXIa:α1at) significantly correlated with albumin levels (r -0.56 p0.04, r -0.70 p 0.005, r -0.77 p 0.0004).

Conclusion(s): Markers of contact and intrinsic pathway activation are significantly higher in patients with liver cirrhosis vs. controls. Complexes of FXIa and FIXa with AT are significantly higher in the portal than in peripheral plasma, possibly indicating heparan-mediated activation.