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Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure
Authors:T LISMAN  K BAKHTIARI  J ADELMEIJER  J C M MEIJERS  R J PORTE  R T STRAVITZ
Institution:1. Surgical Research Laboratory;2. Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen;3. Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;4. Section of Hepatology and Hume‐Lee Transplant Center, Virginia Commonwealth University, Richmond, VA, USA
Abstract:Summary. Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro‐ and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not identical to the changes in patients with chronic liver disease and have not been studied in great detail. Objective: To assess thrombin generation and fibrinolytic potential in patients with ALI/ALF. Methods: We performed thrombin generation tests and clot lysis assays in platelet‐poor plasma from 50 patients with ALI/ALF. Results were compared with values obtained in plasma from 40 healthy volunteers. Results and conclusion: The thrombin generation capacity of plasma from patients with ALI/ALF sampled on the day of admission to hospital was indistinguishable from that of healthy controls, provided thrombomodulin was added to the test mixture. Fibrinolytic capacity was profoundly impaired in patients with ALI/ALF on admission (no lysis in 73.5% of patients, compared with 2.5% of the healthy controls), which was associated with decreased levels of the plasminogen and increased levels of plasminogen activator inhibitor type 1. The intact thrombin generating capacity and the hypofibrinolytic status persisted during the first week of admission. Patients with ALI/ALF have a normal thrombin generating capacity and a decreased capacity to remove fibrin clots. These results contrast with routine laboratory tests such as the PT/INR, which are by definition prolonged in patients with ALI/ALF and suggest a bleeding tendency.
Keywords:acetaminophen  acute liver failure  acute liver injury  coagulation  fibrinolysis  thrombin
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