Fibrinolysis in Patients with Liver Disease

Abstract Patients with liver disease acquire complex changes in their hemostatic system. Historically, these patients were considered to have a bleeding tendency related, in part, to a hyperfibrinolytic state. However, studies using more modern fibrinolysis tests have questioned the presence of a hyperfibrinolytic state in patients with liver disease and its association with bleeding risk. It may be that the sickest patients with liver disease do have fibrinolytic abnormalities. However, the debate on the fibrinolytic state of patients with (decompensated) cirrhosis or critically ill liver disease is complicated by the fact that hypo- and hyperfibrinolysis have been poorly defined. This could, in part, be explained by the lack of reliable tests that assess a patient's fibrinolytic status. Moreover, large clinical studies on the relationship between bleeding and fibrinolysis in patients with liver disease are scarce. Here, we provide an overview of the current knowledge on fibrinolysis in various types of liver diseases and possible implications as a target for therapeutic strategies in liver disease. As antifibrinolytic therapy has been shown to be safe and effective during liver transplantation, it could potentially be of use in patients with (either laboratory-established or suspected) hyperfibrinolysis-related bleeding.

• Publication year

  2021

• Venue

  Seminars in Thrombosis and Hemostasis

• Publication date

  2021-03-26

• Fields of study

  Medicine

• Identifiers
  DOI 10.1055/s-0040-1718924PMID 33772480
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

  2020cited by this paper
• Systematic review with meta‐analysis: the efficacy of tranexamic acid in upper gastrointestinal bleeding

  2020cited by this paper
• VWF/ADAMTS13 Imbalance, But Not Global Coagulation or Fibrinolysis, Is Associated With Outcome and Bleeding in Acute Liver Failure

  2020cited by this paper
• Decreased Fibrinolytic Capacity in Cirrhosis and Liver Transplantation Outcomes

  2019cited by this paper
• Haemostatic Profiles are Similar across All Aetiologies of Cirrhosis

  2019cited by this paper
• Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

  2019cited by this paper
• Inherited disorders of the fibrinolytic pathway.

  2019cited by this paper
• AGA Clinical Practice Update: Coagulation in Cirrhosis.

  2019cited by this paper
• The D‐dimer assay

  2019cited by this paper
• Increased risk of venous thromboembolism in hospitalized patients with cirrhosis due to non-alcoholic steatohepatitis

  2018cited by this paper
• Primary hyperfibrinolysis: Facts and fancies.

  2018cited by this paper
• Plasminogen Activator Inhibitor-1 Reduces Tissue-Type Plasminogen Activator-Dependent Fibrinolysis and Intrahepatic Hemorrhage in Experimental Acetaminophen Overdose.

  2018cited by this paper
• Bleeding complications in acute liver failure

  2018cited by this paper
• Balanced haemostasis with both hypo‐ and hyper‐coagulable features in critically ill patients with acute‐on‐chronic‐liver failure

  2018cited by this paper
• Coagulation Failure in Patients With Acute‐on‐Chronic Liver Failure and Decompensated Cirrhosis: Beyond the International Normalized Ratio

  2018cited by this paper
• Hemorrhagic disorders of fibrinolysis: a clinical review

  2018cited by this paper
• Prevention and Management of Bleeding Risk Related to Invasive Procedures in Cirrhosis

  2018cited by this paper
• Current and Emerging Options for the Management of Inherited von Willebrand Disease

  2017cited by this paper
• Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial.

  2017cited by this paper
• Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases

  2017cited by this paper
• Fibrinolysis shutdown is associated with a fivefold increase in mortality in trauma patients lacking hypersensitivity to tissue plasminogen activator

  2017cited by this paper
• Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity

  2016cited by this paper
• Preserved hemostatic status in patients with non-alcoholic fatty liver disease.

  2016cited by this paper
• Bleeding complications in critically ill patients with liver cirrhosis

  2016cited by this paper
• Coagulation parameters and major bleeding in critically ill patients with cirrhosis

  2016cited by this paper
• Bleeding related to disturbed fibrinolysis

  2016cited by this paper
• Pathophysiology and management of hemostatic alterations in cirrhosis and liver transplantation

  2016cited by this paper
• Decreased Plasma Fibrinolytic Potential As a Risk for Venous and Arterial Thrombosis

  2016cited by this paper
• Increased plasminogen activator inhibitor results in a hypofibrinolytic state in adolescents with obesity: in vivo and ex vivo evidence

  2016cited by this paper
• [Tranexamic acid for upper gastrointestinal bleeding].

  2016cited by this paper
• Fibrinolysis and the control of blood coagulation.

  2015cited by this paper
• Impact of anticoagulation on upper‐gastrointestinal bleeding in cirrhosis. A retrospective multicenter study

  2015cited by this paper
• Classical Notions of Coagulation Revisited in Relation with Blood Losses, Transfusion Rate for 700 Consecutive Liver Transplantations

  2015cited by this paper
• Tranexamic acid for upper gastrointestinal bleeding.

  2014cited by this paper
• Prophylactic anticoagulation for venous thromboembolism in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding

  2014cited by this paper
• Featured Articles for CME Credit December 2014 Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: The spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy

  2014cited by this paper
• Clinical Application of Fibrinolytic Assays

  2014cited by this paper
• No increase in blood transfusions during liver transplantation since the withdrawal of aprotinin

  2014cited by this paper
• Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography

  2013cited by this paper
• The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.

  2013cited by this paper
• Variceal and other portal hypertension related bleeding.

  2013cited by this paper
• Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

  2012cited by this paper
• Bleeding and thrombosis in cirrhotic patients: what really matters?

  2012cited by this paper
• Evidence for an enhanced fibrinolytic capacity in cirrhosis as measured with two different global fibrinolysis tests

  2012cited by this paper
• Fibrin(ogen)-independent role of plasminogen activators in acetaminophen-induced liver injury.

  2012cited by this paper
• Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis.

  2012cited by this paper
• Sepsis, thrombosis and organ dysfunction.

  2012cited by this paper
• Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1.

  2010cited by this paper
• Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences.

  2010cited by this paper
• Thrombocytopenia associated with chronic liver disease.

  2008cited by this paper
• A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.

  2008cited by this paper
• The two tales of coagulation in liver transplantation

  2008cited by this paper
• Fibrinolysis and the risk of venous and arterial thrombosis

  2007cited by this paper
• Plasminogen deficiency

  2007cited by this paper
• Role of the coagulation system in acetaminophen‐induced hepatotoxicity in mice

  2007cited by this paper
• Efficacy and Safety of Antifibrinolytic Drugs in Liver Transplantation: A Systematic Review and Meta‐Analysis

  2007cited by this paper
• Coagulopathy Does Not Fully Protect Hospitalized Cirrhosis Patients from Peripheral Venous Thromboembolism

  2006cited by this paper
• Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: implication in the pathogenesis of thrombotic disorders in the elderly.

  2005cited by this paper
• Regulation of local availability of active tissue‐type plasminogen activator in vivo in man

  2004cited by this paper
• Deficiency of thrombin activatable fibrinolysis inhibitor in cirrhosis is associated with increased plasma fibrinolysis

  2003cited by this paper
• Haemostatic abnormalities in patients with liver disease.

  2002cited by this paper
• Gastroesophageal variceal hemorrhage.

  2001cited by this paper
• Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis.

  2001cited by this paper
• Hyperfibrinolytic activity in hospitalized cirrhotic patients in a referral liver unit

  2000cited by this paper
• Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group.

  2000cited by this paper
• AICF and DIC in Liver Cirrhosis: Expressions of a Hypercoagulable State

  1999cited by this paper
• d-Dimer Assay.

  1998cited by this paper
• High plasma levels of von Willebrand factor as a marker of endothelial perturbation in cirrhosis: Relationship to endotoxemia

  1996cited by this paper
• Outcomes

  1995cited by this paper
• Endothelium releases more von Willebrand factor and tissue-type plasminogen activator upon venous occlusion in patients with liver cirrhosis than in normals.

  1993cited by this paper
• Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis

  1992cited by this paper
• Disseminated intravascular coagulation in liver cirrhosis.

  1992cited by this paper
• Evidence that postoperative fibrinolytic shutdown is mediated by plasma factors that stimulate endothelial cell type I plasminogen activator inhibitor biosynthesis.

  1992cited by this paper
• Simplification of a venous occlusion test.

  1991cited by this paper
• A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis.

  1991cited by this paper
• Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways.

  1990cited by this paper
• Systemic effects of tissue plasminogen activator-associated fibrinolysis and its relation to thrombin generation in orthotopic liver transplantation.

  1989cited by this paper
• Fibrinolysis during liver transplantation in humans: role of tissue-type plasminogen activator.

  1988cited by this paper
• Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage

  1986cited by this paper
• Clinical significance of accelerated fibrinolysis in liver disease.

  1984cited by this paper
• Fibrinolysis at Rest and after Exercise in Hepatic Cirrhosis

  1969cited by this paper
• Pooling of platelets in the spleen: role in the pathogenesis of "hypersplenic" thrombocytopenia.

  1966cited by this paper
• ABNORMAL PLASMINOGEN-PLASMIN SYSTEM ACTIVITY (FIBRINOLYSIS) IN PATIENTS WITH HEPATIC CIRRHOSIS: ITS CAUSE AND CONSEQUENCES.

  1964cited by this paper
• On Plasma Fibrinolytic Activity in Cryptogenetic Splenomegaly

  1957cited by this paper

• Direct oral anticoagulants in patients with advanced cirrhosis: is it time?

  2026cites this paper
• Advances in Perioperative Coagulation Management for Patients with Liver Cirrhosis

  2026cites this paper
• The fibrinolytic system in disease: From molecular pathways to clinical outcomes.

  2025cites this paper
• Platelet protease nexin-1 limits fibrinolysis in patients with cirrhosis

  2025cites this paper
• Patients with cirrhosis have a disbalance between coagulation and fibrinolysis resulting in a prothrombotic phenotype.

  2025cites this paper
• Coagulation Abnormalities in Chronic Liver Disease

  2025cites this paper
• Prediction and prevention of post-procedural bleedings in patients with cirrhosis

  2025cites this paper
• RETRACTED ARTICLE: Elevated FDP levels independently predict poor outcomes in HBV-ACLF patients treated with artificial liver support system therapy

  2025cites this paper
• D-dimers in advanced liver cirrhosis: useful biomarker or not?

  2024cites this paper
• Fibrinolysis-Mediated Pathways in Acute Liver Injury

  2024cites this paper
• Acquired bleeding disorders

  2024cites this paper
• Direct oral anticoagulants in cirrhosis: Rationale and current evidence

  2024cites this paper
• Anticoagulation for Stroke Prevention in Atrial Fibrillation and Treatment of Venous Thromboembolism and Portal Vein Thrombosis in Cirrhosis: Guidance from the SSC of the ISTH.

  2024cites this paper
• Effect of Anticoagulation on The Hepatic Function of Non-Malignant Portal Vein Thrombosis

  2024cites this paper
• Fibrinolytic profile depends on disease severity in pediatric patients with cirrhosis: illustration by 2 different plasma-based fibrinolysis assays

  2024cites this paper
• Fibrinogen dysfunction and fibrinolysis state in patients with hepatitis B-related cirrhosis

  2024cites this paper
• Patient sex and use of tranexamic acid in liver transplantation

  2024cites this paper
• The Prothrombotic Tendency of Metabolic-Associated Fatty Liver Disease.

  2023cites this paper
• Fibrin clot properties and thrombus composition in cirrhosis

  2023cites this paper
• How to assess hemostasis in patients with severe liver disease.

  2023cites this paper
• The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment

  2023cites this paper
• Illustrated State-of-the-Art Capsules of the ISTH 2023 Congress

  2023cites this paper
• Coagulation Management in End-Stage Liver Disease

  2022cites this paper
• Pathophysiology and management of bleeding and thrombosis in patients with liver disease

  2022cites this paper
• Effects of Inflammation on Hemostasis in Acutely Ill Patients with Liver Disease.

  2022cites this paper
• Preface: Altered Fibrinolysis—Clinical Impact and Diagnostic Challenges

  2021cites this paper
• Hemostasis and Fibrinolysis following Aneurysmal Subarachnoid Hemorrhage: A Systematic Review on Additional Knowledge from Dynamic Assays and Potential Treatment Targets

  2021cites this paper