NATURAL ANTICOAGULANTS AND THE LIVER

The regulation of blood coagulation is dependent on a complex interpla y between procoagulant, anticoagulant and fibrinolytic proteins. Most of these proteins are synthesised in the liver and their levels are al tered in patients with liver disease. The liver also plays an importan t role in the regulation of haemostasis throughout the clearance of ac tivated clotting factors. It is therefore not surprising that the crit ically balanced coagulation system is dysregulated in patients with li ver disease. In moderate liver failure bleeding disorders predominate, whereas in more advanced liver disease intravascular coagulation is c ommonly observed and contributes to the overall dysregulation of blood coagulation. In some patients, liver disease can be primarily caused by an abnormality of the coagulation system. These patients usually ha ve a hypercoagulable state caused by a deficiency of a component of th e natural anticoagulant system. These include protein C, protein S and antithrombin m. More recently, activated protein C resistance caused by a point mutation in the Factor V gene has been identified as an imp ortant risk factor for thrombosis. In these patients the abnormal Fact or V is resistant to cleavage by activated protein C resulting in ongo ing uncontrolled procoagulant drive. Both hepatic and portal vein thro mbosis have been reported in these patients. Appropriate management of these patients should include a thorough assessment of their natural anticoagulant proteins and exclusion of activated protein C resistance as the cause of their thrombotic disorder.