Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity

Lisman, Ton; Bongers, T.N.; Adelmeijer, Jelle; Janssen, Harry L.A.; Maat, Moniek P.M. de; Groot, Philip G. de; Leebeek, Frank W.G.

doi:10.1002/hep.21231

Cited by 541 publications

(533 citation statements)

References 32 publications

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“…In these patients, the rate of spontaneous recanalization of portal veins was exceptionally high (70%), compared with only 1/41 in the prospective study by Luca et al [202]. Retrospective studies [43,181,203,205] yielded discordant data but overall indicated poorer survival in patients with stable or progressive PVT, if left untreated [2,4,5]. In addition, PVT in liver transplant candidates correlated with increased mortality after liver transplantation [206].…”

Section: Impact Of Portal Vein Thrombosis On the Natural History Of Cmentioning

confidence: 93%

“…Patients with cirrhosis present with variable degrees of thrombocytopenia [11] and increased levels of the adhesive protein von Willebrand factor (VWF) which facilitates in vitro platelets to adhere and aggregate normally [2]. When the platelet count was adjusted to a standard value of 100 × 10 9 /L, platelet-rich plasma from patients with cirrhosis generated in vitro as much thrombin as that of healthy subjects [12].…”

Section: Platelet Countmentioning

confidence: 99%

“…The net effect of these changes is a rebalanced hemostasis. However, this hemostatic profile is unstable, and patients can be tipped toward both bleeding and thrombosis under certain conditions [1][2][3][4][5]. Thus, there is growing evidence that proper understanding of the hemostatic pathways in liver disease requires a global perspective which account for the complexity of hemostasis, with dynamic interactions between pro-coagulant and anti-coagulant factors.…”

Section: Introductionmentioning

confidence: 99%

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Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

Andriulli

Tripodi

Angeli

et al. 2016

Digestive and Liver Disease

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a b s t r a c tPatients with cirrhosis present with hemostatic alterations secondary to reduced availability of procoagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent jury. The statements presented here highlight strengths and weaknesses of current laboratory tests to assess bleeding and thrombotic risk in cirrhotic patients, the pathophysiology of hemostatic perturbations in this condition, and outline the optimal management of bleeding and thrombosis in patients with liver cirrhosis.

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Section: Impact Of Portal Vein Thrombosis On the Natural History Of Cmentioning

confidence: 93%

Section: Platelet Countmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

Andriulli

Tripodi

Angeli

et al. 2016

Digestive and Liver Disease

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“…23 However, the platelet defects get balanced by increased levels of factor VIIIa/vWF, which increases platelet adhesion. 24 Three recent independent studies have been published specifically evaluating the prevalence of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with cirrhosis. [25][26][27] The incidence of DVT/PE ranged from 0.5% to 1.87% in these studies.…”

Section: Pathophysiologymentioning

confidence: 99%

Portal Vein Thrombosis in Cirrhosis

Raja

Jacob

Asthana

2014

Journal of Clinical and Experimental Hepatology

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Portal vein thrombosis (PVT) is being increasingly recognized in patients with advanced cirrhosis and in those undergoing liver transplantation. Reduced flow in the portal vein is probably responsible for clotting in the spleno-porto-mesenteric venous system. There is also increasing evidence that hypercoagulability occurs in advanced liver disease and contributes to the risk of PVT. Ultrasound based studies have reported a prevalence of PVT in 10-25% of cirrhotic patients without hepatocellular carcinoma. Partial thrombosis of the portal vein is more common and may not have pathophysiological consequences. However, there is high risk of progression of partial PVT to complete PVT that may cause exacerbation of portal hypertension and progression of liver insufficiency. It is thus, essential to accurately diagnose and stage PVT in patients waiting for transplantation and consider anticoagulation therapy. Therapy with low molecular weight heparin and vitamin K antagonists has been shown to achieve complete and partial recanalization in 33-45% and 15-35% of cases respectively. There are however, no guidelines to help determine the dose and therapeutic efficacy of anticoagulation in patients with cirrhosis. Anticoagulation therapy related bleeding is the most feared complication but it appears that the risk of variceal bleeding is more likely to be dependent on portal pressure rather than solely related to coagulation status. TIPS has also been reported to restore patency of the portal vein. Patients with complete PVT currently do not form an absolute contraindication for liver transplantation. Thrombectomy or thromboendovenectomy is possible in more than 75% of patients followed by anatomical end-to-end portal anastomosis. When patency of the portal vein and/or superior mesenteric vein is not achieved, only non-anatomical techniques (reno-portal anastomosis or cavo-portal hemitransposition) can be performed. These techniques, which do not fully reverse portal hypertension, are associated with higher morbidity and mortality risks in the short term. ( J CLIN EXP HEPATOL 2013;4:320-331)

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“…VWF collagen binding activity was determined with an in-house ELISA assay (intra-and inter-assay CV of 2.9% and 3.8%) as described previously (12). The collagen binding activity of pooled normal plasma was set at 100% and the activity measured in patient samples was expressed as a percentage of pooled normal plasma.…”

Section: Vwf and Adamts13 Assaysmentioning

confidence: 99%

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

Hugenholtz

Ruitenbeek

Adelmeijer

et al. 2015

American Journal of Transplantation

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An unbalance between the platelet‐adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off‐pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation‐specific effects from those generally accompanying open‐chest surgeries by comparing results with 11 patients undergoing off‐pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra‐large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft.

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Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity

Cited by 541 publications

References 32 publications

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference

Portal Vein Thrombosis in Cirrhosis

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

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