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

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

doi:10.1016/j.jhep.2016.06.002

Cited by 76 publications

(55 citation statements)

References 55 publications

(82 reference statements)

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“…Furthermore, years ago we showed that patients with cirrhosis possess a procoagulant imbalance that can be detected in vitro as the resistance to the anticoagulant action of thrombomodulin (the physiological activator of protein C) in a modified thrombin generation procedure . This procoagulant imbalance, which was independently confirmed depends on the elevated levels of factor VIII, reduced levels of protein C and the increased factor VIII/protein C ratio, which are typical features of patients with cirrhosis. Recent studies showed that the procoagulant imbalance detected as an increased factor VIII/protein C ratio independently predicts outcome in patients with cirrhosis and that the resistance to thrombomodulin is associated with an increased risk of developing de novo portal vein thrombosis …”

Section: Discussionmentioning

confidence: 96%

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

Tripodi

D’Ambrosio

Padovan

et al. 2017

Liver International

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Treatment with DAAs in HCV-related cirrhosis results in improvement of the individual pro- and anticoagulants. It can be hypothesised that the net effect does not substantially modify their balance (as shown by the unchanged thrombin generation in the presence of thrombomodulin) but makes it more stable and less amenable to be perturbed as presumably occurs before treatment when there is a partial deficiency for both.

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Section: Discussionmentioning

confidence: 96%

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

Tripodi

D’Ambrosio

Padovan

et al. 2017

Liver International

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“…Increased plasma VWF levels are closely associated with poor outcome in patients with cirrhosis, and VWF levels are associated with fibrosis in the general population (La Mura et al , 2011; Ferlitsch et al , 2012; Maieron et al , 2014; Plompen et al , 2015; Kalambokis et al , 2016). Building on this clinical association, we provide the first experimental evidence that VWF directly contributes to liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Among the hemostatic molecules disturbed in both acute and chronic liver disease is Von Willebrand factor (VWF), a glycoprotein that functions to bridge platelets with an exposed collagen surface. Several studies report that plasma levels of VWF (Reuken et al , 2015) are increased in patients with acute liver failure, as well as cirrhosis, with high levels predictive of poor outcome in this patient population (La Mura et al , 2011; Ferlitsch et al , 2012; Hugenholtz et al , 2013; Maieron et al , 2014; Kalambokis et al , 2016). Suggesting a functional connection, VWF levels are associated with the severity of liver fibrosis in the general population (Plompen et al , 2015).…”

Section: Introductionmentioning

confidence: 99%

Von Willebrand factor deficiency reduces liver fibrosis in mice

Joshi

Kopec

Ray

et al. 2017

Toxicology and Applied Pharmacology

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Liver diseases are associated with complex changes in the hemostatic system and elevated levels of the platelet-adhesive protein Von Willebrand factor (VWF) are reported in patients with acute and chronic liver damage. Although elevated levels of VWF are associated with fibrosis in the general population, the role of VWF in acute and chronic liver injury has not been examined in depth in experimental settings. We tested the hypothesis that VWF deficiency inhibits experimental liver injury and fibrosis. Wild-type (WT) and VWF-deficient mice were challenged with carbon tetrachloride (CCl4) and the impact of VWF deficiency on acute liver injury and chronic liver fibrosis was determined. VWF deficiency did not significantly affect acute CCl4-induced hepatocellular necrosis in mice. Chronic CCl4 challenge, twice weekly for 6 weeks, significantly increased hepatic stellate cell activation and collagen deposition in livers of WT mice. Interestingly, hepatic induction of several profibrogenic and stellate cell activation genes was attenuated in VWF-deficient mice. Moreover, birefringent sirius red staining (indicating type I and III collagens) and type I collagen immunofluorescence indicated a reduction in hepatic collagen deposition in CCl4-exposed VWF-deficient mice compared to CCl4-exposed WT mice. The results indicate that VWF deficiency attenuates chronic CCl4-induced liver fibrosis without affecting acute hepatocellular necrosis. The results are the first to demonstrate that VWF deficiency reduces the progression of liver fibrosis, suggesting a mechanistic role of elevated plasma VWF levels in cirrhosis.

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“…vWf levels and the VIII factor-to-PC ratio are as predictive of mortality as MELD. Thrombogenic mechanisms that operate within the cirrhotic liver might underlie the progression of portal hypertension and adverse clinical outcomes in patients with cirrhosis[42]. …”

Section: Discussionmentioning

confidence: 99%

Serum omentin and vaspin levels in cirrhotic patients with and without portal vein thrombosis

Kukla

Waluga

Żorniak

et al. 2017

WJG

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AIMTo investigate serum omentin and vaspin levels in cirrhotic patients; and to assess the relationship of these levels with hemostatic parameters, metabolic abnormalities, cirrhosis severity and etiology.METHODSFifty-one cirrhotic patients (17 with portal vein thrombosis) were analyzed. Serum omentin and vaspin levels were measured with commercially available direct enzyme-linked immunosorbent assays (ELISAs). To assess platelet activity, the following tests were performed using a MULTIPLATE®PLATELET FUNCTION ANALYZER: (1) an ADP-induced platelet activation test; (2) a cyclooxygenase dependent aggregation test (ASPI test); (3) a von Willebrand factor and glycoprotein Ib-dependent aggregation (using ristocetin) test (RISTO test); and (4) a test for thrombin receptor-activating peptide-6 induced activation of the thrombin receptor, which is sensitive to IIb/IIIa receptor antagonists.RESULTSOmentin, but not vaspin, serum concentrations were significantly decreased in patients with portal vein thrombosis (PVT) (P = 0.01). Prothrombin levels were significantly increased in patients with PVT (P = 0.01). The thrombin receptor activating peptide (TRAP) test results were significantly lower in the PVT group (P = 0.03). No significant differences in adipokines serum levels were found regarding the etiology or severity of liver cirrhosis assessed according to the Child-Pugh or Model of End-Stage Liver Disease (MELD) scores. There was a significant increase in the TRAP (P = 0.03), ASPI (P = 0.001) and RISTO high-test (P = 0.02) results in patients with lower MELD scores. Serum omentin and vaspin levels were significantly down-regulated in patients without insulin resistance (P = 0.03, P = 0.02, respectively). A positive relationship between omentin and vaspin levels were found both when all of the patients were analyzed (r = 0.41, P = 0.01) and among those with PVT (r = 0.94, P < 0.001).CONCLUSIONSerum omentin levels are increased in patients without PVT. Cirrhosis origin and grade do not affect omentin and vaspin levels. The analyzed adipokines do not influence platelet activity.

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

Cited by 76 publications

References 55 publications

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

Evaluation of coagulation during treatment with directly acting antivirals in patients with hepatitis C virus related cirrhosis

Von Willebrand factor deficiency reduces liver fibrosis in mice

Serum omentin and vaspin levels in cirrhotic patients with and without portal vein thrombosis

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