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

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• 作者：Georgios N. Kalambokis¹ ; ^{gkalambo@cc.uoi.gr" class="auth_mail" title="E-mail the corresponding author} ; Aikaterini Oikonomou² ; Leonidas Christou¹ ; Nikolaos I. Kolaitis² ; Epameinondas V. Tsianos¹ ; ³ ; Dimitrios Christodoulou³ ; Gerasimos Baltayiannis³
• 关键词：MELD ; Model for End-stage Liver Disease ; vWF-Ag ; von Willebrand factor antigen ; PC ; protein C ; AT ; antithrombin ; FVIII ; factor VIII ; PH ; portal hypertension ; VB ; variceal bleeding ; AUC ; area under the curve
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：65
• 期：5
• 页码：921-928
• 全文大小：856 K

文摘

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.