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.(ABSTRACT TRUNCATED AT 250 WORDS)

High circulating D-dimers are associated with ascites and hepatocellular carcinoma in liver cirrhosis

“…Some authors suggest the exchange of some coagulation and fibrinolytic proteins between plasma and ascitic fluid [1,11] . Violi et al propose that hyperfibrinolysis in cirrhotic patients might represent a state of low grade disseminated intravascular coagulation secondary to the passage of gut absorbed bacterial material into the systemic circulation [12] . On the basis of this finding, Piscaglia et al argue that the association between high plasma D-dimers and ascites might be due only to more advanced liver disease with portal hypertension favouring bacterial translocation.…”

Fibrinolysis in patients with fulminant hepatic failure

“…However, it is uncertain whether this is a primary event or secondary to coagulation activation. 1 We report evidence showing the consumption of coagulation factors causes some of the coagulation defects observed in patients with severe loss of hepatic function. Antithrombin-III (AT-III) and thrombin-antithrombin (TAT) serum levels were measured in 10 consecutive patients with fulminant hepatic failure who had impaired coagulation, shown by a markedly elevated prothrombin time.…”

Hyperfibrinolysis and the risk of hemorrhage in stable cirrhotic patients

“…PAI-1 may be unchanged, reduced, or elevated [3,16,17]. This partly depends on the deterioration of liver functions and the acute phase reactions that can decrease [18] and increase [19] the PAI-1 levels, respectively. Furthermore, the fibrinolytic tests have been wellknown for their variability including the diurnal variation.…”