Plasmin-mediated proteolysis of von Willebrand factor in patients with acute and chronic liver disease

Abstract

Background: In patients with acute and chronic liver disease, von Willebrand factor (VWF) antigen levels are markedly elevated, whereas a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity is often reduced. The role of VWF proteolysis by other proteases, such as plasmin, remains unclear. Objectives: To investigate whether plasmin-mediated VWF cleavage occurs in patients with acute and chronic liver disease and to assess its association with VWF parameters, ADAMTS13 activity, and fibrinolytic markers. Methods: Plasma samples from 191 patients with stable or decompensated cirrhosis, acute liver failure or acute liver injury, acute-on-chronic liver failure, or sepsis without underlying chronic liver disease and 41 healthy controls were analyzed. VWF antigen and collagen-binding activity, ADAMTS13 antigen and activity, ADAMTS13-cleaved VWF, plasmin-cleaved VWF (cVWF), plasmin-α2-antiplasmin complexes, and D-dimer were measured by ELISA. Results: VWF antigen levels were higher in all patient groups and increased with disease severity. VWF activity was also elevated but was not proportional to VWF antigen level. ADAMTS13 activity and specific activity decreased with worsening disease. cVWF was undetectable in healthy controls and patients with stable cirrhosis but was increased in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure. cVWF levels correlated with D-dimer but not with plasmin-α2-antiplasmin complexes or VWF activity. Conclusion: cVWF is detectable in patients with decompensated cirrhosis, acute liver failure or injury, and acute-on-chronic liver failure but not in those with stable cirrhosis or healthy individuals. Its association with D-dimer supports a link with fibrinolytic activation. These findings suggest that cVWF may reflect disease severity or ongoing microvascular thrombosis in patients with advanced liver disease.