The aim of this study was to evaluate whether there plain, for instance, the so-called hyperdynamic circulais endothelial dysfunction in patients with cirrhosis and tion, which is characterized by hypotension, low vascuto detect the mechanism that may account for it. We lar resistance, and increased cardiac output and is measured plasma levels of von Willebrand factor (vWF), thought to be attributable to increased vascular release a marker of endothelial perturbation, and endotoxin, of nitric oxide, 3,4 a vasodilating substance secreted by which releases vWF from endothelial cells in vitro, in endothelial and vascular smooth muscle cells.5 Endo-32 patients (18 men, 14 women, aged 39-70 years) with thelial perturbation might also explain the coagulation cirrhosis classified as mild (class A, n Å 10), moderate changes seen in cirrhosis. It is known that the clinical In cirrhosis, changes in hemostasis might be medibetween vWF antigen and endotoxemia (r Å .92; P ated by endotoxemia, which is elevated perhaps as a Å .0001). In 20 selected patients, vWF antigen and endoresult of reduced hepatic clearance.12 There is evidence toxemia were measured before and after 7 days of stanthat endotoxemia induces vascular secretion of nitric dard therapy (n Å 10) or standard therapy plus nonabsorbable antibiotics. There was a significant decrease of oxide and enhances activation of clotting. An in vitro vWF antigen (P õ .02) concomitantly with the decrease study demonstrated that endotoxin enhances nitric oxof endotoxemia (P õ .006) in patients taking nonabsorb-ide synthase expression in endothelial cell, 13 whereas able antibiotics. Human umbilical vein endothelial cells an in vivo study showed that in cirrhotic patients the incubated in vitro with 125 to 500 pg/mL endotoxin re-reduction of endotoxemia by nonabsorbable antibiotics leased vWF antigen into the medium dose dependently. is associated with a significant decrease of serum levels These results demonstrate that there is endothelial per-of nitrite and nitrate.2 In addition, in experimental turbation in cirrhosis and that endotoxemia may play a studies in which endotoxin was infused into humans, key role in its occurrence. (HEPATOLOGY 1996;23:1377-there was a significant increase of the prothrombin 1383.) fragment 1 / 2, 14 a marker of in vivo thrombin generation, suggesting that endotoxin may heighten coagulaThere is indirect evidence that there may be endothetion enzyme activity. lial perturbation in cirrhosis, which might explain All of these data indicate that endotoxemia is the some clinical and biological changes occurring in this trigger of a sequence of events inducing endothelial, clinical setting. karyocytes, which is considered to be a marker of endoAddress reprint requests to: Francesco Violi, M.D., I Clinica Medica, Polithelial perturbation. 15 We also attempted to reduce the

No abstract

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 micrograms/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 less than 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p less than 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p less than 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p less than 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p less than 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

This study shows that in SLE patients, aPL positivity is associated with an ongoing prothrombotic state only in the presence of endothelial perturbation. Our findings also suggest that aPLs and TNF-alpha might cooperate in inducing endothelial perturbation.

SummaryCirrhotic patients with decompensated state and high serum levels of fibrin(ogen) degradation products are at high risk of bleeding. The aim of this study was to further analyse the relationship between hyperfibrinolysis and bleeding in cirrhosis by measuring plasma values of D-dimer and tissue plasminogen activator (t-PA) activity. One-hundred-twelve cirrhotic patients with oesophageal varices and without previous upper-gastrointestinal bleeding entered the study and were followed-up for 3 years. Patients were considered to have hyperfibrinolysis if they concomitantly had high values of D-dimer and t-PA activity. During the follow-up 34 (30%) patients bled. They had more severe liver failure (p = 0.0001) and variceal size (p = 0.0031) and higher prevalence of ascites (p = 0.0003), varices with red signs and hyperfibrinolysis (p = 0.0001) than patients who did not bleed. Multivariate analysis disclosed hyperfibrinolysis as the only marker predictive of bleeding (Hazard Ratio = 42.5, p <0.001). Our findings suggest that screening for hyperfibrinolysis may be useful to identify cirrhotic patients at risk of bleeding.