Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + PATHOGENESIS Download Section PDF Listen +++ ++ Loss of hepatic parenchymal cells leads to decreased plasma levels of all plasma coagulation factors except factor VIII and von Willebrand factor. Thrombocytopenia occurs frequently and is usually a result of splenic sequestration (see Chap. 74), but may also be caused by an autoimmune mechanism, disseminated intravascular coagulation (DIC), folic acid deficiency, and decreased platelet production. In some patients, thrombocytopenia due to thrombopoietin (TPO) deficiency and platelet dysfunction contribute to the hemostatic abnormalities. Enhanced fibrinolysis is common, and appears to be caused by complex pathogenetic mechanisms, including release and impaired clearance of plasminogen activators. Dysfibrinogenemia is relatively frequently found in patients with chronic liver disease. Patients with chronic liver disease may develop DIC. + CLINICAL FEATURES Download Section PDF Listen +++ ++ Patients with chronic liver disease may present with purpura, epistaxis, gingival bleeding, and/or menorrhagia. Bleeding may follow trauma or surgical procedures, especially in sites with high fibrinolytic activity, such as the urogenital tract or oral mucosa. Patients with acute viral or toxic hepatitis usually develop abnormal bleeding only if the disease is fulminant. Bleeding from esophageal varices requires primary attention to the bleeding site as well as efforts to correct the hemostatic abnormalities. The coagulopathy of liver disease may also predispose the patient to thromboembolic complications. + LABORATORY FEATURES Download Section PDF Listen +++ ++ Table 84–1 summarizes the laboratory abnormalities that can be found in patients with chronic liver disease. These abnormalities may both contribute to bleeding or thrombosis. Determination of plasma levels of factors V, VII, and VIII may help differentiate liver disease (factor VIII levels normal or increased; factors V and VII decreased), vitamin K deficiency (factor VII decreased; factors V and VIII normal), and DIC (all decreased). ++Table Graphic Jump LocationTABLE 84–1ALTERATIONS IN THE HEMOSTATIC SYSTEM IN PATIENTS WITH LIVER DISEASE THAT CONTRIBUTE TO BLEEDING (LEFT) OR COUNTERACT BLEEDING (RIGHT)View Table||Download (.pdf) TABLE 84–1 ALTERATIONS IN THE HEMOSTATIC SYSTEM IN PATIENTS WITH LIVER DISEASE THAT CONTRIBUTE TO BLEEDING (LEFT) OR COUNTERACT BLEEDING (RIGHT) Changes That Impair Hemostasis Changes That Promote Hemostasis Thrombocytopenia Elevated levels of VWF Platelet function defects Decreased levels of ADAMTS-13 Enhanced production of nitric oxide and prostacyclin Elevated levels of factor VIII Low levels of factors II, V, VII, IX, X, and XI Decreased levels of protein C, protein S, antithrombin, and heparin cofactor II Vitamin K deficiency Low levels of plasminogen Dysfibrinogenemia Low levels of α2-antiplasmin, factor XIII, and TAFI Elevated t-PA levels VWF, von Willebrand factor; ADAMTS-13, a disintegrin-like and metalloprotease with thrombospondin domain 13; TAFI, thrombin-activatable fibrinolysis inhibitor; t-PA, tissue type plasminogen activator.Source: Williams Hematology, 8th ed, Chap. 129, Table 129–1, p. 2096. + THERAPY Download Section PDF Listen +++ ++ Correction of coagulation is only required in case of bleeding or when an invasive procedure has to be performed. Replacement of all the deficient coagulation factors may be attempted with fresh-frozen plasma, but large volumes of plasma are required and volume overload may occur. The risk of transmission of infectious agents can be minimized by using solvent-detergent–treated plasma. Prothrombin complex concentrates may be used to correct deficiency of the vitamin K–dependent factors, but do not contain factor V. These preparations may (theoretically) result in thrombosis and can transmit blood-borne microorganisms. Vitamin K administration is effective in patients with vitamin K deficiency. Due to a relative resistance to vitamin K, high doses (10 mg) are advised. Platelet transfusion may be useful in correcting thrombocytopenia, but splenic sequestration may reduce the yield to ineffective levels. Antifibrinolytic agents may prevent bleeding in patients with mucosal bleeding or who require dental extraction, but enhance the risk of thrombosis in patients with DIC. ++ For a more detailed discussion, see Ton Lisman and Philip G. de Groot: Hemostatic Dysfunction Related to Liver Diseases and Liver Transplantation, Chap. 129, p. 2095 in Williams Hematology, 8th ed.