Coagulopathy of Chronic Liver Disease

Abstract

opposing drivers (Fig. 1), but the mechanistic significance of the parallel decrease of both procoagulants and anticoagulants in patients with chronic liver disease escaped attention for many years. As a consequence, chronic liver disease is still considered the epitome of acquired bleeding disorders and is featured as such in most hematology textbooks. The basic laboratory tests of coagulation (i.e., measurement of the prothrombin time and activated partial-thromboplastin time) have been used to assess the risk of bleeding. However, their results are poorly correlated with the onset and duration of bleeding after liver biopsy or other potentially hemorrhagic procedures. 2-7 These test results are also poorly correlated with the occurrence of gastrointestinal bleeding, the prototype of hemorrhagic events in patients with end-stage liver disease. 8,9 Additional evidence that argues against the clinical relevance of the coagulation defects as detected by conventional laboratory tests in determining the bleeding tendency in these patients can be drawn from the natural history of liver transplantation. In the past, this major surgical procedure required massive transfusions of plasma and other blood products to correct the marked abnormalities on tests of hemostasis (assessments of coagulation, platelets, and fibrinolysis) observed both preoperatively and perioperatively. The need for transfusions, however, has declined considerably over time — not because of any substantial change in medication, but rather because of improved surgical procedures. 10 Finally and most important, randomized clinical trials involving patients with chronic liver disease have shown that powerful procoagulant agents, such as recombinant activated factor VII, fail to control bleeding from the upper intestinal tract 11,12 or bleeding during liver transplantation, 13,14 even though the postinfusion prothrombin time is considerably shortened. 11 In this review, we consider the evidence regarding the balance in the hemostatic system (involving coagulation, platelets, and fibrinolysis).