Thrombin-Activatable Fibrinolysis Inhibitor Deficiency in Cirrhosis Is Not Associated With Increased Plasma Fibrinolysis

Lisman, Ton; Leebeek, Frank W.G.; Mosnier, Laurent O.; Bouma, Bonno N.; Meijers, Joost C. M.; Janssen, Harry L.A.; Nieuwenhuis, H. K.; Groot, Philip G. de

doi:10.1053/gast.2001.25481

Cited by 267 publications

(244 citation statements)

References 36 publications

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“…Recent studies have documented the limitations of conventional tests of hemostasis. 21,22,[34][35][36] Accurate assessment of hemostatic mechanisms would require the use of more global tests, such as the endogenous thrombin generation potential, 34,35 thromboelastogram 37 and thrombin-activatable fibrinolysis inhibitor 36 rather than prothrombin time, factor levels, or platelet counts. Use of rFVIIa can be an expensive intervention in a setting such as the one used in this trial.…”

Section: Discussionmentioning

confidence: 99%

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

et al. 2008

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on behalf of the International Study Group on rFVIIa in UGI Hemorrhage A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B ‫؍‬ 26%, C ‫؍‬ 74%) were randomized equally to: placebo; 600 g/kg rFVIIa (200 ؉ 4؋ 100 g/kg); or 300 g/kg rFVIIa (200 ؉ 100 g/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P ‫؍‬ 0.37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 g/kg rFVIIa compared with placebo (odds ratio 0.31, 95% confidence interval ‫؍‬ 0.13-0.74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 g/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. Conclusion: Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups. (HEPATOLOGY 2008;47:1604-1614

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Section: Discussionmentioning

confidence: 99%

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

et al. 2008

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“…Cirrhosis has been associated with laboratory changes suggesting hyperfibrinolysis (i.e., increased t-PA and reduced PI or TAFI), but also with changes suggesting hypofibrinolysis (i.e., reduced plasminogen and increased PAI). Despite conflicting data, the balance of fibrinolysis is likely restored by concomitant changes in the pro-and anti-fibrinolytic drivers [3,32,33].…”

Section: Fibrinolysismentioning

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%

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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“…This is found to be well correlated with proneness towards stroke, IHD, thrombo-embolic diseases and is an independent predictor of both fatal and nonfatal IHD [4][5][6]. Thus assessment of fibrinolysis time is one of the most important markers of cardiovascular health [7].…”

Section: Introductionmentioning

confidence: 99%

Fibrinolytic Activity of Blood and its Determinants in Healthy Medical Students

Siddqui

Shoeb²,

Bose

2015

JCDR

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Thrombin-Activatable Fibrinolysis Inhibitor Deficiency in Cirrhosis Is Not Associated With Increased Plasma Fibrinolysis

Cited by 267 publications

References 36 publications

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial

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

Fibrinolytic Activity of Blood and its Determinants in Healthy Medical Students

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