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In patients with acute liver failure or chronic liver disease, many changes in the hemostatic system occur. The liver is the site of synthesis of nearly all coagulation factors, both pro- and anticoagulant proteins. A reduced synthesis function of the liver will lead to reduced levels of these factors in circulation. In addition, the liver is involved in the clearance of many activated coagulation factors and protein-inhibitor complexes from the circulation, which, in turn, can lead to activation of the coagulation system if liver function is impaired. Furthermore, the liver is involved in the synthesis and clearance of pro- and antifibrinolytic proteins, which may lead to a shift in the balance of the fibrinolytic system. Also primary hemostasis might be affected in liver disease because of thrombocytopenia and impaired platelet function, which is frequently encountered in these patients. It is evident that patients with liver disease have frequent bleeding episodes, mainly in the gastrointestinal tract, such as variceal bleeding. It has been a longstanding dogma that patients with liver disease are at a high risk of bleeding caused by the above mentioned hemostatic changes. However, in recent years this cause of the bleeding tendency has been questioned because of the concomitant reductions of pro- and anticoagulant factors and pro- and antifibrinolytic factors. More recent studies using more sophisticated coagulation tests showed that thrombin generation is normal in patients with chronic liver failure and that some may even have a prothrombotic phenotype. This led to the development of a model of a rebalanced hemostatic system in these patients, which may have immediate implications for treatment. Hematologists and other clinicians taking care of patients with acute liver failure of chronic liver disease, such as cirrhosis, are still faced with the questions whether these patients need correction of the changes in hemostasis before interventions such as paracentesis, biopsies, dental care, and surgery. It was generally believed that replacement therapy with frozen plasma or prothrombin complex concentrate was indicated. However, based on these new findings, physicians should now be more restrictive in the use of hemostatic agents and blood products in these patients both in liver disease and during liver transplantation.


Acronyms and Abbreviations

ADAMTS13, a disintegrin-like and metalloprotease with thrombospondin domain 13; aPTT, activated partial thromboplastin time; DDAVP, 1-deamino-8-d-arginine vasopressin; DIC, disseminated intravascular coagulation; FFP, fresh-frozen plasma; HAT, hepatic artery thrombosis; INR, international normalized ratio; ISI, international sensitivity index; MELD, model of end-stage liver disease; PAI-1, plasminogen activator inhibitor 1; PFA, platelet function analyzer; PT, prothrombin time; PVT, portal vein thrombosis; TAFI, thrombin-activatable fibrinolysis inhibitor; t-PA, tissue-type plasminogen activator; VWF, von Willebrand factor.


The liver plays a central role in the hemostatic system. Liver parenchymal cells are the site of synthesis of most coagulation factors (except factor VIII), the natural inhibitors of coagulation, including protein C, protein S, and antithrombin, and essential components of the fibrinolytic system, such as plasminogen, α2-antiplasmin, and thrombin activatable fibrinolysis inhibitor ...

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