Imbalance of von Willebrand factor and its cleaving protease ADAMTS13 during systemic inflammation superimposed on advanced cirrhosis. (3rd September 2014)

• Record Type: Journal Article
• Authors: Reuken, Philipp A.; Kussmann, Anna; Kiehntopf, Michael; Budde, Ulrich; Stallmach, Andreas; Claus, Ralf A.; Bruns, Tony
• Is Part Of: Liver international. Volume 35(2015)Supplement 1
• Page Start: 37
• Page End: 45
• Publication Date: 2014-09-03
• Subjects: Liver -- Periodicals; Liver -- Diseases -- Periodicals; 616.362
• DOI: 10.1111/liv.12657
• Languages: English
• ISSNs: 1478-3223

Abstract

<abstract abstract-type="main" id="liv12657-abs-0001"> <title>Abstract</title> <sec id="liv12657-sec-0001" sec-type="section"> <title>Background & Aims</title> <p>Systemic inflammation in advanced cirrhosis represents a spectrum ranging from subclinical pathological bacterial translocation and immune activation to overt bacterial infection and sepsis. We hypothesized that systemic inflammation in cirrhosis is accompanied by a failure of ADAMTS13 to control the prothrombotic function of von Willebrand factor (VWF), which is increased in portal hypertension and hepatic fibrosis.</p> </sec> <sec id="liv12657-sec-0002" sec-type="section"> <title>Methods</title> <p>Patients with Child A cirrhosis (<italic>n</italic> = 25), Child B/C cirrhosis without clinical features of systemic inflammation (<italic>n</italic> = 31), and Child B/C cirrhosis with overt bacterial infections or systemic inflammatory response syndrome (<italic>n</italic> = 24) were analysed for ADAMTS13 and associated parameters and were followed to determine transplant‐free survival.</p> </sec> <sec id="liv12657-sec-0003" sec-type="section"> <title>Results</title> <p>Plasma concentration and activity of ADAMTS13 were decreased in patients with systemic inflammation. Furthermore, ADAMTS13 inversely correlated with the extent of bacterial translocation and the severity of acute‐phase reaction. As a function of reduced ADAMTS13 activity and increased VWF antigen, plasma from patients with superimposed inflammation strongly aggregated the platelet receptor glycoprotein Ib in presence of ristocetin. VWF:RCo correlated with higher concentrations of leucocytes and lipopolysaccharide‐binding protein, organ dysfunction, augmented turnover of cross‐linked intravascular fibrin, and the occurrence of acute kidney injury during follow‐up. VWF:RCo of 390% or more predicted transplant‐free survival in univariate analysis [HR = 8.24 (3.30–20.54)] and after adjustment for MELD [HR = 3.58 (1.30–9.88)]. However, adverse outcome was not associated with the accumulation of high‐molecular weight VWF multimers.</p> </sec> <sec id="liv12657-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Systemic inflammation complicating advanced cirrhosis is accompanied by reduced activity of ADAMTS13 promoting a prothrombotic function of VWF, which can be employed to predict clinical outcome.</p> </sec> </abstract>