Sarah Bos1,2, Bente van den Boom1, Pieter W Kamphuisen3,4, Jelle Adelmeijer1, Hans Blokzijl2, Tim Schreuder2, Ton Lisman1. 1. Surgical Research Laboratory and Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands. 4. University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract
BACKGROUND AND AIM: Patients with cirrhosis may acquire profound changes in haemostasis. Although haemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed aetiology. As thrombotic events appear more common in some aetiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that haemostatic changes might be different across aetiologies. PATIENTS AND METHODS: We studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease [ALD], 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of haemostasis, thrombin generation assays, fibrin permeability assays and a plasma-based fibrinolytic assay were performed. RESULTS: All patients had comparable severity of disease according to their Model for End-Stage Liver Disease score (9 [7-11]). Plasma levels of von Willebrand factor were substantially elevated across all aetiologies, with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels comparable to controls. Thrombin generation capacity was elevated in all aetiologies, most profoundly in ALD. Fibrin permeability was decreased in all aetiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all aetiologies. CONCLUSION: Our in-depth haemostatic profiling of primary, secondary and tertiary haemostasis in a group of patients with Childs-Turcotte-Pugh A/B cirrhosis showed no large differences between aetiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their aetiology. Georg Thieme Verlag KG Stuttgart · New York.
BACKGROUND AND AIM: Patients with cirrhosis may acquire profound changes in haemostasis. Although haemostatic changes in cirrhosis have been extensively studied, most studies were performed in groups of patients with mixed aetiology. As thrombotic events appear more common in some aetiologies of disease, notably non-alcoholic steatohepatitis (NASH) and cholestatic disease, we hypothesized that haemostatic changes might be different across aetiologies. PATIENTS AND METHODS: We studied 109 patients with cirrhosis (31 cholestatic liver disease, 23 NASH, 37 alcoholic liver disease [ALD], 18 viral hepatitis) and 44 healthy controls. Patients with malignancy were excluded. Routine diagnostic tests of haemostasis, thrombin generation assays, fibrin permeability assays and a plasma-based fibrinolytic assay were performed. RESULTS: All patients had comparable severity of disease according to their Model for End-Stage Liver Disease score (9 [7-11]). Plasma levels of von Willebrand factor were substantially elevated across all aetiologies, with a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels comparable to controls. Thrombin generation capacity was elevated in all aetiologies, most profoundly in ALD. Fibrin permeability was decreased in all aetiologies, which was accompanied by elevated fibrinogen levels. Clot lysis times were prolonged in NASH and cholestatic disease. Plasma levels of individual proteins were similarly altered in all aetiologies. CONCLUSION: Our in-depth haemostatic profiling of primary, secondary and tertiary haemostasis in a group of patients with Childs-Turcotte-Pugh A/B cirrhosis showed no large differences between aetiologies, and was consistent with a general hypercoagulable profile in patients with mild cirrhosis. These results suggest that patients with cirrhosis have an increased risk of thrombosis, irrespective of their aetiology. Georg Thieme Verlag KG Stuttgart · New York.
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