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Chronic or acute liver failure caused by, for example, viral hepatitis, alcohol abuse, or acetaminophen intoxication, results in substantial changes in the hemostatic system. Because the liver is involved in the synthesis of procoagulant and antifibrinolytic proteins, reduced amounts of these proteins are found if the synthetic function of the liver is compromised. Furthermore, a diseased liver has a reduced ability to clear activated hemostatic proteins, activators of fibrinolysis, or protein–inhibitor complexes from the circulation. A reduced platelet count and impaired platelet function are also commonly observed in patients with liver disease. These defects in hemostatic pathways are counteracted by concomitant defects in anticoagulant and profibrinolytic systems. Furthermore, highly elevated levels of von Willebrand factor that may compensate for impaired platelet function are present in patients with liver disease. Prolonged prothrombin time (PT) and activated partial thromboplastin time do not correlate very well with a bleeding tendency because these tests do not measure the reduced activity of the physiologic anticoagulants like protein C, protein S, and antithrombin. More sophisticated tests of hemostasis, such as total thrombin generation tests, can be normal in patients with stable liver disease. Thus, in many patients there is “rebalanced” hemostasis represented by limited bleeding during surgery including liver transplantation and sometimes even by thromboembolic complications. The new concept of rebalanced hemostasis has been translated to a more restricted prophylactic use of blood components in patients undergoing liver transplantation.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: 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; PT, prothrombin time; PVT, portal vein thrombosis; TAFI, thrombin-activatable fibrinolysis inhibitor; TFPI, tissue factor pathway inhibitor; t-PA, tissue-type plasminogen activator; VWF, von Willebrand factor.

The liver plays a central role in hemostasis and thrombosis. Liver parenchymal cells are the site of synthesis of most coagulation factors, the physiologic inhibitors of coagulation, protein C, protein S, and antithrombin, and essential components of the fibrinolytic system, plasminogen, α2-antiplasmin, and thrombin activatable fibrinolysis inhibitor (TAFI). The liver also regulates hemostasis and fibrinolysis by clearing activated coagulation factors and enzyme-inhibitor complexes from the circulation. Therefore, when liver dysfunction occurs in patients with liver disease, a complicated hemostatic derangement ensues, which can lead to bleeding, thrombosis, or neither bleeding nor thrombosis.



A mild to moderate thrombocytopenia (platelet counts between 50,000 and 100,000/µL) is frequently observed in patients with liver disease. The main causes for thrombocytopenia are increased platelet sequestration in the spleen because of congestive splenomegaly related to portal hypertension1,2 and reduced thrombopoietin production by the liver.3 Alternative mechanisms of thrombocytopenia include a reduced platelet half-life, ...

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