High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: Relationship to endotoxemia

✍ Scribed by D Ferro; C Quintarelli; A Lattuada; R Leo; M Alessandroni; P M Mannucci; F Violi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 229 KB
• Volume: 23
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510230613

✦ Synopsis

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 (class B, n Å 16), or severe (class C, n Å 6) according to course of cirrhosis is complicated by a hyperfibrinolytic Child-Pugh's classification. vWF antigen (P õ .0001) and

state, 6 primary or secondary to intravascular activaendotoxemia (P õ .0001) progressively increased from A to class C; but the increase of vWF antigen was not tion of coagulation. 7,8 Endothelial cells may play a role strictly related to liver failure, as shown by the lack of in the pathogenesis of this state, because they secrete correlation between vWF and several indexes of liver fibrinolytic substances such as tissue plasminogen actiprotein synthesis. Analysis of the vWF subunit showed vator, 9 procoagulant substances such as tissue factor, 10 no sign of proteolytic fragmentation of the molecule. or adhesive proteins such as von Willebrand factor Multimeric analysis indicated intact vWF multimeric (vWF). 11 structure. In all patients, there was a strong correlation

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 nonabsorbide 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 rereduction 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 perof 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;23:1377there was a significant increase of the prothrombin

1383.)

Abbreviations: vWF, von Willebrand factor; RiCof, ristocetin cofactor. in patients with cirrhosis has never been explored. We