Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Hemostasis and global fibrinolytic capacity in chronic liver disease Sirin Aytac a , Cansel Turkay b , Nuket Bavbek c and Ali Kosar d Accelerated fibrinolysis associated with liver disease can be demonstrated by various tests that are either nonspecific in liver disease or that demonstrate only an extrinsic pathway. In the present study we used a new method to assess the global fibrinolytic capacity (GFC) of both the intrinsic and extrinsic pathways in patients with chronic liver disease. Forty patients with the diagnosis of chronic liver disease were included in the study. Seventeen age-matched and gender-matched healthy control individuals were enrolled as a control group. The GFC was studied with semiquantitative macrolatex agglutination. The study population consisted of 40 patients with chronic liver disease (group 1, patients with chronic hepatitis; group 2, patients with cirrhosis; group 3, patients with hepatocellular carcinoma), mean age 53.3 W 13 years, and a control group (group 4) consisting of 17 healthy individuals (mean age 55 W 12.2 years). The GFC was significantly higher in patients than in control individuals (13.8 W 9 mg/ml, 13.6 W 11 mg/ml, 14.1 W 14 mg/ml, 1.9 W 2.2 mg/ml, respectively; P < 0.05). There was no difference between the patient groups (P > 0.05). There was a significant positive relationship between the GFC and the prothrombin time and activated partial thromboplastin time values (P < 0.05). A negative correlation was also observed between the GFC and thrombocyte counts (P < 0.05). In conclusion, our results suggest that patients with chronic liver disease have hyperfibrinolysis, as reflected by the increased GFC. Elucidation of the GFC in chronic liver disease can reflect the net fibrinolytic capacity of those patients who are prone to hyperfibrinolysis resulting in bleeding tendencies and hemorrhages. Blood Coagul Fibrinolysis 18:623–626 ß 2007 Lippincott Williams & Wilkins. Blood Coagulation and Fibrinolysis 2007, 18:623–626 Keywords: global fibrinolytic capacity, liver a Department of Gastroenterology, Guven Hospital, Ankara, b Department of Gastroenterology, c Department of Internal Medicine and d Department of Hematology, Fatih University Medical School, Ankara, Turkey Correspondence to Dr Nu ¨ ket Bavbek, Harbiye Mahallesi Nig ˘ de Sokak, No. 46/2 Dikmen, Ankara, Turkey Tel: +90 312 4829166; fax: +90 312 2306080; e-mail: ntbavbek@yahoo.com Received 10 June 2006 Revised 15 May 2007 Accepted 19 May 2007 Introduction The liver plays a central role in hemostasis by synthesiz- ing most coagulation factors, coagulation inhibitors, fibri- nolytic proteins and their inhibitors. Furthermore, the reticuloendothelial system of the liver is responsible for clearing all activated clotting factors, the activation com- plexes of both coagulation and fibrinolysis, and the degradation products of fibrin and fibrinogen [1]. Patients who suffer from liver disease may develop a wide spec- trum of coagulopathy. Accelerated fibrinolysis associated with liver disease was first described over 80 years ago by Goodpasture [2]. A relationship between hyperfibrinoly- sis and mucosal [3] or fatal [4,5] bleeding has been reported, which suggests that hyperfibrinolysis in liver disease predisposes patients to bleeding tendencies and even to fatal hemorrhages. Although the pathogenesis of hyperfibrinolysis in patients with liver disease is not yet clearly defined, studies have shown that it may involve delayed hepatic clearance of tissue plasminogen activator [6–9] and impaired synthesis of plasminogen activator inhibitor-1 [6,7,10] and a 2 -antiplasmin [11,12]. Hyperfibrinolysis can be demonstrated by various clinical tests, including the shortened euglobin lysis time, the whole blood clot lysis time, and the plasma clot lysis time, which are nonspecific in patients with liver disease. The tissue plasminogen activator level and activity, plasminogen activator inhibi- tor or tissue plasminogen activator–plasminogen activa- tor inhibitor-1 complex levels, plasminogen and plasmin levels, and a 2 -antiplasmin or plasmin– a 2 -antiplasmin levels are used as indicators of fibrinolytic activity [1,4,10,13,14]. In these tests the extrinsic pathway of plasminogen activator activation is demonstrated. In the present study we used a new method to assess the global fibrinolytic capacity (GFC) of both intrinsic and extrinsic pathways in patients with chronic liver disease. The GFC is a recently developed assay that is reflected by the amount of generated D-dimer when the fibrino- lysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. The GFC is sensitive to reflecting all molecular components involved in the process of fibrinolysis [15– 21]. The GFC assay allows exploration of the fibrinolytic potential of plasma and evaluation of fibrinolytic dysfunc- tions in a reliable manner. The aim of the present study was to assess whether patients with chronic liver disease have any alterations in the GFC and the other essential hemostatic Original article 623 0957-5235 ß 2007 Lippincott Williams & Wilkins