An Imbalance of Pro- vs Anti-Coagulation Factors in Plasma From Patients With Cirrhosis

Tripodi, Armando; Primignani, Massimo; Chantarangkul, Veena; Dell’Era, Alessandra; Clerici, Marigrazia; Franchis, Roberto de; Colombo, Massimo; Mannucci, Pier Mannuccio

doi:10.1053/j.gastro.2009.08.045

Cited by 473 publications

(481 citation statements)

References 23 publications

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“…The ratio of endogenous thrombin potential with or without thrombomodulin parallels the severity of cirrhosis, and correlates with increased levels of factor VIII, reduced levels of protein C, and their ratios [29]. These results were confirmed when, instead of thrombomodulin, Protac (a non-physiologic protein C activator) was used for testing [37].…”

Section: Thrombin Generation Assaysmentioning

confidence: 71%

“…When evaluated by TGA, patients with cirrhosis have the potential to generate as much thrombin as healthy subjects after thrombomodulin addition [1,4]. Patients with cirrhosis and relatively high levels of thrombin generation present with a hypercoagulable state in vitro [29] and may be at risk of thrombotic events. By the same token, patients with relatively low levels may be at increased hemorrhagic risk.…”

Section: Thrombin Generation Assaysmentioning

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: Thrombin Generation Assaysmentioning

confidence: 71%

Section: Thrombin Generation Assaysmentioning

confidence: 99%

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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“…The coagulation system in patients with ILF is perceived to be unstable compared with healthy individuals, who have both sufficient and properly functioning procoagulants and anticoagulants. Studies of coagulation factors in patients with cirrhosis have revealed decreased amounts and disturbed procoagulant and anticoagulant activity 21, 22. The relative deficiency of both procoagulants and anticoagulants may cause increased thrombosis or bleeding depending on the prevailing circumstantial conditions 23…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Wang

Kuo

et al. 2018

JAHA

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BackgroundPatients with impaired liver function (ILF) were excluded from clinical trials that investigated non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOACs in atrial fibrillation patients with ILF.Methods and ResultsA cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOACs and warfarin in patients with normal liver function and ILF, respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65–0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60–0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF, compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49–0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding.ConclusionsIn atrial fibrillation patients with ILF, NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

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“…The ratio of the most powerful procoagulant (factor VIII) and anticoagulant (protein C) in plasma showed a balance strongly in favor of factor VIII, which indicates hypercoagulability. 16 Factor VIII concentrations have been reported to be higher in patients with worse Child-Pugh grade. 16 A recent study reported that high levels of factor VIII were independently associated with cirrhotic PVT, with odds ratio for thrombosis being 6.0 if factor VIII levels were above 129 IU/dl.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Various clinical as well as in-vitro studies have actually shown that some patients with cirrhosis may have a thrombotic potential. 16 All procoagulant factors except factor VIII are reduced in hepatic insufficiency. By contrast, the levels of factor VIII/vWF are increased in cirrhosis.…”

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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An Imbalance of Pro- vs Anti-Coagulation Factors in Plasma From Patients With Cirrhosis

Cited by 473 publications

References 23 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

Efficacy and Safety of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study

Portal Vein Thrombosis in Cirrhosis

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