von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia

Georgios N Kalambokis; Aikaterini Oikonomou; Leonidas Christou; Nikolaos I Kolaitis; Epameinondas V Tsianos; Dimitrios Christodoulou; Gerasimos Baltayiannis

doi:10.1016/j.jhep.2016.06.002

von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia

J Hepatol. 2016 Nov;65(5):921-928. doi: 10.1016/j.jhep.2016.06.002. Epub 2016 Jun 11.

Authors

Georgios N Kalambokis¹, Aikaterini Oikonomou², Leonidas Christou³, Nikolaos I Kolaitis², Epameinondas V Tsianos⁴, Dimitrios Christodoulou⁵, Gerasimos Baltayiannis⁵

Affiliations

¹ 1st Division of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece. Electronic address: gkalambo@cc.uoi.gr.
² Hematology Laboratory Unit of Molecular Biology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
³ 1st Division of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece.
⁴ 1st Division of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece; Division of Gastroenterology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
⁵ Division of Gastroenterology, Medical School, University of Ioannina, 45110 Ioannina, Greece.

PMID: 27297911
DOI: 10.1016/j.jhep.2016.06.002

Abstract

Background & aims: Several lines of evidence suggest that the hemostatic disorders of cirrhosis may have a significant clinical impact. We investigated the independent predictive value of components of the hemostatic system on the occurrence of ascites, variceal bleeding (VB), and survival.

Methods: One hundred and two patients with thrombocytopenia (Child-Pugh class A/B/C: 34/34/34) were enrolled. Platelet counts, factors (F) II, V, VII, and VIII, antithrombin, protein C (PC), FVIII-to-PC ratio as an index of procoagulant imbalance, von Willebrand factor antigen (vWF-Ag), and model for end-stage liver disease (MELD) were evaluated. Two multivariate analyses were performed: one excluding (model 1) and one including MELD (model 2).

Results: Higher vWF-Ag levels and FVIII-to-PC ratios were the most prominent hemostatic disorders in patients with cirrhosis. Increased levels of vWF-Ag and FVIII, and higher FVIII-to-PC ratios independently predicted the presence of ascites and varices at baseline. Independent predictors of ascites and VB during follow-up were vWF-Ag (model 1/2: p=0.001/p=0.009 and p=0.008/p=0.01, respectively) and FVIII-to-PC ratio (model 1/2: p=0.003/p=0.02 and p=0.01/p=0.03, respectively). vWF-Ag (model 1/2: p=0.007/p=0.002), FVIII-to-PC ratio (model 1/2: p=0.001/p=0.01), and MELD (p=0.02) independently predicted mortality. Patient groups with significantly higher probability of new-onset ascites, VB, and mortality were identified by certain cut-offs of vWF-Ag (213%, 466%, and 321%, respectively) and FVIII-to-PC ratio (1.99, 3.29, and 2.36, respectively). vWF-Ag and FVIII-to-PC ratio equaled MELD in mortality prediction.

Conclusions: Advanced cirrhosis is characterized by increased thrombotic potential. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, VB, and mortality. Targeting hypercoagulability could improve the outcome of patients with cirrhosis.

Lay summary: Higher von Willebrand factor antigen (vWF-Ag) levels and factor VIII-to-protein C (FVIII-to-PC) ratio are the prominent hemostatic disorders in patients with cirrhosis. vWF-Ag and FVIII-to-PC ratio independently predict new-onset ascites, variceal bleeding, and mortality in these patients.

Keywords: Cirrhosis; Decompensation; Mortality; Procoagulant imbalance; von Willebrand factor antigen.

MeSH terms

Esophageal and Gastric Varices
Factor VIII
Gastrointestinal Hemorrhage
Humans
Liver Cirrhosis*
Thrombocytopenia*
von Willebrand Factor

Substances

von Willebrand Factor
Factor VIII