6 As with the procoagulant and anticoagulant forces, there is a delicate balance between the profibrinolytic and antifibrinolytic pathways. Fibrinolysis counters thrombus formation. The many proteins Sunitinib molecular weight involved in this clot degradation pathway are affected by hepatic dysfunction. Plasminogen binds to fibrin on a clot, and fibrinolysis is activated by the conversion of plasminogen to plasmin by tissue plasminogen activator (tPA). Levels are increased in liver disease secondary to reduced hepatic clearance
and increased release by activated endothelium.4 Conversely, plasmin activator inhibitor-1 (PAI-1), which inhibits tPA, has increased levels. Although this would appear to have a neutralizing effect, the enzyme activity of tPA relative to PAI-1 can be increased7, favoring a hyperfibrinolytic state. Multiple proteins with an antifibrinolytic effect are decreased
in liver disease, including a2 plasmin inhibitor, thrombin activatable fibrinolysis inhibitor and factor XIII.4 The flux of prothrombotic and antithrombotic tendencies brought about by hepatic dysfunction is accentuated by additional stresses, such as infections, thrombocytopenia and the underlying liver condition. Bacterial infections in cirrhotic patients have been shown to exert a heparin-like effect.8 Thrombocytopenia ABT-263 ic50 occurs as a result of splenomegaly and sequestration, bone marrow suppression, reduced thrombopoietin production and immune-mediated destruction. In addition, metabolic syndrome, steatosis and non-alcoholic steatohepatitis can create a hypercoagulable state.9 It is clear from the above discussion that a myriad of factors can influence bleeding and thrombotic tendencies in cirrhotic liver disease. There are reductions in prothrombotic and antithrombotic factors which, although they can be balanced, reduce the normal buffer that maintains hemostasis. Patients with cirrhosis are easily tipped towards thrombotic or bleeding complications,
so there is clear clinical utility in being able to predict those at risk. How do we determine the risk of hemostatic complications based on conventional blood tests? selleck products The measure of individual component protein levels does not reflect the physiological effect that these each have in situ, which is paramount in determining the risk of a bleeding or thrombotic event. In this edition of the Journal of Gastroenterology and Hepatology, Zhang and colleagues10 endeavor to identify changes in hemostatic proteins that indicate underlying portal vein thrombosis (PVT), a serious complication that occurs in the later stages of decompensated liver disease, particularly including those with complicating hepatocellular carcinoma. This group measured various key proteins involved in thrombogenesis and fibrinolysis, as well as PT, APTT and D-dimer.