Is there a rationale for treatment of chronic liver disease with antithrombotic therapy?

Hugenholtz, Greg C. G.; Porte, Robert J.; Lisman, Ton

doi:10.1016/j.blre.2014.10.002

Cited by 37 publications

(49 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, previous studies have shown decreased fibrin clot permeability to be associated with both arterial and thrombotic diseases . In turn, this study supports a potential prothrombotic role of fibrin clots in patients with acute and chronic liver failure, opposing the effects of reduced production of coagulation factors . The prolonged clotting times and decreased clot permeability in both plasma and samples of purified fibrinogen suggest that structural alterations of the fibrinogen molecule itself underpin the changes in fibrin structure.…”

Section: Discussionsupporting

confidence: 81%

Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen

Hugenholtz

Macrae

Adelmeijer

et al. 2016

Journal of Thrombosis and Haemostasis

112

View full text Add to dashboard Cite

To cite this article: Hugenholtz GCG, Macrae F, Adelmeijer J, Dulfer S, Porte RJ, Lisman T, Ari€ ens RAS. Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen. J Thromb Haemost 2016; 14: 1054-66. Essentials Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however , clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. Abstract. Background and Objectives: Patients with cirrho-sis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods: We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrino-gen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results: Tissue factor and throm-bin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in tur-bidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot perme-ability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions: Delayed clot formation in cir-rhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrino-gen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition.

show abstract

Section: Discussionsupporting

confidence: 81%

Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen

Hugenholtz

Macrae

Adelmeijer

et al. 2016

Journal of Thrombosis and Haemostasis

112

View full text Add to dashboard Cite

show abstract

“…Представление о том, что при циррозе антикоагулянтный статус защищает больных от тромбозов и тромбоэмболий, является ошибочным [5]. Больные с циррозом печени имеют повышенный риск венозных тромбозов, в том числе воротной вены [6,7].…”

Section: внутренние болезниunclassified

“…При циррозе наблюдается снижение синтеза антикоагулянтов: протеина С, протеина S, антитромбина III [1,7,8]. Частичный дефицит антикоагулянтов сопровождается усилением генерации тромбина, что совместно со снижением уровня протеина С и антитромбина ведёт к прокоагулянтному статусу [7,9].…”

Section: Abstract: Liver Cirrhosis Thrombosis Thromboembolism Antunclassified

Anticoagulation in Patients with Liver Cirrhosis (Literature Review)

Енисеева

2019

Acta biomedica scientifica

View full text Add to dashboard Cite

Liver cirrhosis is accompanied by complex hemostatic disorders with an increase in the risk of both hemorrhagic and thrombotic complications. Reduced coagulation protein synthesis, such as factors II, VII, IX, X and thrombocytopenia are associated with an increased risk of bleeding. Reducing the synthesis of such anticoagulants as protein C, protein S, antithrombin III is accompanied by increased generation of thrombin, which leads to procoagulant status, increased risk of venous thrombosis, pulmonary embolism, and portal vein thrombosis. Activation of the coagulation cascade increases the risk of thrombosis, and also plays an important role in liver damage, contributing to the progression of fibrosis. Cirrhosis increases the risk of thromboembolic complications of atrial fibrillation.Anticoagulants are necessary for the prevention of thrombosis and thromboembolic complications. However, there are no large prospective studies. There is insufficient data on the safety of anticoagulant therapy in cirrhosis. There are difficulties in monitoring anticoagulation in the application of vitamin K antagonists and low molecular weight heparins.The review presents the available data on the use of warfarin, unfractionated heparin, low molecular weight heparins and direct oral anticoagulants in patients with liver cirrhosis, indicating the need for prevention of venous thrombosis in patients with risk factors, the possibility of preventing decompensation of cirrhosis, reducing the frequency of cardioembolic strokes in patients with atrial fibrillation.

show abstract

“…In patients with compensated cirrhosis, the balance between procoagulant and anticoagulant factors is relatively stable, whereas in decompensated cirrhosis, the balance tips toward a procoagulant state . In patients with decompensated cirrhosis, synthesis of anticoagulant factors such as protein C and S are decreased, and procoagulants such as factor VIII, thrombin, tissue factor, and von Willebrand factor are increased, overall resulting in a prothrombotic state …”

Section: Key Pointsmentioning

confidence: 99%

PRO: Patients With Advanced Cirrhosis and Portal Vein Thrombosis Should Receive Anticoagulation

García–Tsao

2018

Clinical Liver Disease

View full text Add to dashboard Cite

show abstract

Is there a rationale for treatment of chronic liver disease with antithrombotic therapy?

Cited by 37 publications

References 124 publications

Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen

Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen

Anticoagulation in Patients with Liver Cirrhosis (Literature Review)

PRO: Patients With Advanced Cirrhosis and Portal Vein Thrombosis Should Receive Anticoagulation

Contact Info

Product

Resources

About