PLATELETS FROM PATIENTS WITH LIVER-CIRRHOSIS EXHIBIT A DEFECT IN THE VONWILLEBRAND FACTOR-BINDING DOMAIN

In this study, we examined the platelet von Willebrand factor (vWF)-binding domain in patients with liver cirrhosis. Direct binding studies were performed with the monoclonal antibody (mab) AN51 with specificity for the glycoprotein (GP) lbalpha. Specific binding of AN51 to intact washed platelets was monitored by an enzyme-linked immunoassay (ELISA). Half-maximum binding to intact washed platelets occurred at concentrations as low as 94 +/- 24 ng/ml; N = 12). Binding saturation analysis of with AN51 revealed a more than fifty percent reduction of AN51-binding sites (p < 0.001) in cirrhosis (N = 13) as compared to sex- and age-matched healthy controls (N = 12). These data demonstrate an impairment of the platelet surface vWF-binding domain in patients with liver cirrhosis. The resulting defect in primary haemostasis, i.e. the vWF-mediated attachment of platelets to the exposed subendothelium, is expected to contribute to the increased risk of haemorrhagic complications in these patients.