Chronic liver disease is associated with clinical bleeding and decrease in most pro-coagulant level factors, with the exceptions of factor VIII and the Von Willebrand factor which are elevated.
Decreased pro-coagulant factors are accompanied by decreases in natural occurring anticoagulants such as anti-thrombin and protein C.
Coagulation tests such as prothrombin time and activated partial thromboplastin time are used to assess the risk of bleeding in chronic liver disease, but are poorly correlated with onset and duration of bleeding following biopsy of the liver or other potentially hemorrhagic procedures.
Prothrombin time and activated partial thromboplastin time results are also poorly correlated with the occurrence of gastrointestinal bleeding seen in end-stage liver disease.
Plasma from patients with cirrhosis generates as much thrombin as plasma from healthy subjects, provided that thrombin is measured by methods that reflect the action of both procoagulants and anticoagulants.
Thrombin generation is down regulated by thrombomodulin a transmembrane protein situated on vascular endothelial cells acting as the main physiologic activator of protein C.
The prothrombin time using plasma and other reagents does not contain thrombomodulin, and therefore measures thrombin generated in plasma by procoagulant drivers, but not the thrombin inhibited by anticoagulant drivers, especially protein C, which is not fully activated in the absence of thrombomodulin.
The prothrombin time does not represent the balance of coagulation in vivo and is inadequate to assess risk of bleeding in coagulopathy of liver disease.
A relative deficiency of both pro and anti-coagulation system drivers associated with fragile balance and may be associated with bleeding or thrombosis, in the patient with liver disease.
Thrombocytopenia is another cause of bleeding in chronic liver disease.