HYPERFIBRINOLYSIS INCREASES THE RISK OF GASTROINTESTINAL HEMORRHAGE IN PATIENTS WITH ADVANCED CIRRHOSIS

Sixty-one patients with different degrees of liver failure, 23 with Child-Pugh class B and 38 with Child-Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10-mu-g/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 +/- 8.7 ng/ml vs. 5.41 +/- 1.9 ng/ml; p < 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p < 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p < 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p < 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p < 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p < 0.02) than patients without hyperfibrinolysis. During the follow-up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively. Cox's multiple regression model showed that positive fibrinogen degradation products was the best bleeding predictor (beta coefficient = 3.9 +/- 0.7 S.E.M., p < 0.001). This study indicates that in cirrhosis the presence of hyperfibrinolysis should be regarded as an important warning sign of gastrointestinal bleeding.