Plasma von Willebrand factor levels predict in-hospital survival in patients with acute-on-chronic liver failure
- 8 November 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Indian Journal of Gastroenterology
- Vol. 35 (6), 432-440
- https://doi.org/10.1007/s12664-016-0708-2
Abstract
Background and Aims Circulating levels of von Willebrand factor (vWF) predict mortality in patients with cirrhosis. We hypothesized that systemic inflammation in acute-on-chronic liver failure (ACLF) will stimulate endothelium, increase vWF levels, and promote platelet microthrombi causing organ failure. Methods In this prospective study, we correlated plasma vWF levels with organ failure, liver disease severity, sepsis, and systemic inflammatory response syndrome (SIRS) and also analyzed if vWF levels predicted in-hospital composite poor outcome (i.e. death/discharged in terminal condition/liver transplantation) in consecutive ACLF patients. Results Twenty-one of the 50 ACLF patients studied had composite poor outcome. ACLF patients had markedly elevated vWF antigen and activity (sevenfold and fivefold median increase, respectively) on days 1 and 3. Median ratio of vWF to a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) activity on day 1 was significantly higher in ACLF patients (11.2) compared to 20 compensated cirrhosis patients (3.3) and healthy volunteers (0.9). On day 1, area under ROC curve (AUROC) to predict composite poor outcome of hospital stay for ACLF patients for vWF antigen, vWF activity, and model for end-stage liver disease (MELD) score were 0.63, 0.68, and 0.74, respectively. vWF activity correlated better with liver disease severity (MELD score, ACLF grade) and organ failure (Sequential Organ Failure Assessment [SOFA] score) than vWF antigen; in contrast, neither vWF antigen nor activity correlated with platelet count, sepsis, or SIRS. Conclusions vWF levels are markedly elevated, correlate with organ failure, and predict in-hospital survival in ACLF patients. This data provides a mechanistic basis for postulating that vWF-reducing treatments such as plasma exchange may benefit ACLF patients.Keywords
Funding Information
- Science and Engineering Research Board (EMR/2015/000570)
This publication has 49 references indexed in Scilit:
- Prognostic significance of von willebrand factor in cirrhosis: A possible mechanismJournal of Hepatology, 2013
- Acute-on chronic liver failureJournal of Hepatology, 2012
- N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and miceJCI Insight, 2011
- Prediction value of model for end‐stage liver disease scoring system on prognosis in patients with acute‐on‐chronic hepatitis B liver failure after plasma exchange and lamivudine treatmentJournal of Gastroenterology and Hepatology, 2008
- Comprehensive analysis of ADAMTS13 in patients with liver cirrhosisThrombosis and Haemostasis, 2008
- Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchangeBest Practice & Research Clinical Haematology, 2006
- Changes in ADAMTS13 (von-Willebrand-factor-cleaving protease) activity after induced release of von Willebrand factor during acute systemic inflammationThrombosis and Haemostasis, 2005
- Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpuraBlood, 2004
- Changes in von Willebrand factor–cleaving protease (ADAMTS13) activity after infusion of desmopressinBlood, 2003
- The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failureIntensive Care Medicine, 1996