Cirrhosis patients have a coagulopathy that is associated with decreased clot formation capacity

BACKGROUND: The coagulopathy in cirrhosis is associated with thrombosis and bleeding. OBJECTIVES: To gain better insights into the coagulopathy in patients with cirrhosis, we evaluated plasma thrombin generation and whole blood clot formation in a cross-sectional study. METHODS: Blood was collected from 73 patients with all-cause cirrhosis (Child-Pugh-A n=52, B n=15, C n=6) and 20 healthy controls. Activity of the coagulation pathways were measured with assays for factor VIIa and factor IXa-antithrombin and factor Xa-antithrombin complexes, respectively. Thrombin generation by Calibrated Automated Thrombography was determined in platelet poor plasma using a 1 or 5 pM tissue factor trigger with/without thrombomodulin. ROTEM-measurements were performed in whole blood triggered with 35 pM tissue factor without/with 175ng/ml tissue Plasminogen Activator (the latter refered to as'tPA-ROTEM'). RESULTS: We observed an increased generation of factor VIIa and a moderately elevated amount of factor IXa (in complex with antithrombin) without apparent increase in factor X activation in patients with cirrhosis. In accordance with this prothrombotic state, markers of thrombin generation potential were also increased upon increasing severity of cirrhosis. In the whole blood clotting assay we observed delayed clot formation and decreased clot strength associated with increased cirrhosis severity. No significant differences were found for tPA-ROTEM parameters of clot degradation. CONCLUSION: These results indicate that cirrhosis patients have an overall procoagulant plasma milieu but a decreased whole blood clot formation capacity with an apparently unaltered resistance to clot lysis. This article is protected by copyright. All rights reserved.