Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis

Abstract

This study explored the relationship between clotting activation and tissue plasminogen activator and its inhibitor in cirrhotic patients with different degrees of liver failure. Sixty-seven patients (40 men, 27 women; age = 31–77 yr) with cirrhosis diagnosed by liver biopsy were divided into three subgroups (A, B and C) on the basis of Child-Pugh classification. Tissue plasminogen activator antigen and activity, plasminogen activator inhibitor antigen and activity, fibrin/fibrinogen degradation products, and D-dimer were measured in each patient. Forty-two patients with normal levels of fibrin/fibrinogen degradation products and D-dimer showed significant progressive decreases of plasminogen activator inhibitor antigen levels (p < 0.01) and activity (p < 0.0001) from class A to class C. This decrease was significantly related to prothrombin time (p < 0.003). Tissue plasminogen activator values were not different in the three Child classes. Twenty-five patients (7 class B and 18 class C) with high circulating values of fibrin/fibrinogen degradation products and D-dimer had higher values of tissue plasminogen activator antigen (20.0 ± 10.1 ng/ml vs. 5.9 ± 3.0 ng/ml; p < 0.0001) and activity (6.9 ± 2.2 U/ml vs. 2.1 ± 1.3 U/ml;p < 0.0001) and lower values of plasminogen activator inhibitor antigen (6.9 ± 4.1 ng/ml vs. 14.8 ± 5.6 ng/ml; p < 0.0001) and activity (4.1 ± 2.8 U/ml vs. 9.8 ± 3.7 U/ml; p < 0.0001) than did patients with normal values of fibrin/fibrinogen degradation products and D-dimer. We conclude that cirrhotic patients without systemic signs of hyperfibrinolysis exhibited progressive decreases of plasminogen activator inhibitor levels, suggesting that its blood levels are strongly related to liver function. The clear-cut imbalance between tissue plasminogen activator and plasminogen activator inhibitor in patients with high circulating levels of D–dimer indicates that hyperfibrinolysis may be due mainly to clotting activation. (HEPATOLOGY 1993;17:78–83.)