Plasma von Willebrand factor levels predict in-hospital survival in patients with acute-on-chronic liver failure.
OBJECTIVE
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.
Department of Hepatology, Christian Medical College, Vellore, 632 004, India.
K S
KS
Prasanna
Department of Hepatology, Christian Medical College, Vellore, 632 004, India.
Ashish
A
Goel
Wellcome Biochemistry, Christian Medical College, Vellore, 632 004, India.
G Jayakumar
GJ
Amirtharaj
Wellcome Biochemistry, Christian Medical College, Vellore, 632 004, India.
Anup
A
Ramachandran
Wellcome Biochemistry, Christian Medical College, Vellore, 632 004, India.
K A
KA
Balasubramanian
Haemostasis Research Unit, Haematology Department, University College London, London, UK.
Ian
I
Mackie
Department of Hepatology, Christian Medical College, Vellore, 632 004, India.
Uday
U
Zachariah
Department of Hepatology, Christian Medical College, Vellore, 632 004, India.
K G
KG
Sajith
Department of Hepatology, Christian Medical College, Vellore, 632 004, India.|Liver Unit, University Hospital Birmingham, Birmingham, UK.
Elwyn
E
Elias
Department of Hepatology, Christian Medical College, Vellore, 632 004, India. eapen@cmcvellore.ac.in.
C E
CE
Eapen
D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D013534:Survival; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D014841:von Willebrand Factor
ADAMTS13; Endothelial activation; Von Willebrand factor