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Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thrombelastography

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      Abstract

      Background/Aims: Patients with primary biliary cirrhosis and primary sclerosing cholangitis survive variceal bleeding better than patients with alcoholic cirrhosis and have less bleeding at liver transplantation. Recently, patients with primary biliary cirrhosis have been found to have a higher incidence of thrombosis in the portal venous tree. We hypothesized that primary biliary cirrhosis and primary sclerosing cholangitis patients may be hypercoagulable.
      Methods: We used thrombelastography, which is a simple technique for evaluating whole blood clotting and fibrinolysis, to establish if hypercoagulability was present, defined by thrombelastography values greater than 2SD over controls: r<19 mm (this reflects plasma clotting factors), maximum amplitude (ma) > 60 mm, and alpha angle > 43° (these reflect platelets and fibrinogen levels). We evaluated 47 primary biliary cirrhosis and 21 primary sclerosing cholangitis patients, 40 with non-cholestatic cirrhosis and 40 healthy subjects as control groups with thrombelastography, full blood count, prothrombin time, partial thromboplastin time and, fibrinogen concentrations. In those with hypercoagulability we evaluated protein S, C, anti-thrombin III levels and activated protein C phenotype.
      Results: All three thrombelastography abnormalities present together defined hypercoagulability: these were found in 13 of 47 (28%) primary biliary cirrhosis and in nine of 21 (43%) primary sclerosing cholangitis patients independent of cirrhosis, and bilirubin concentration, but in only 2 of 40 (5%) patients with non-cholestatic cirrhosis and in none of the healthy controls (p<0.03 and p<0.0002, respectively). There was no correlation between the fibrinogen concentration (which was normal in all patients) or platelet count and the thrombelastography parameters. Only six of the 22 hypercoagulable patients had lower than normal values of protein S, C or antithrombin III. Activated protein C phenotype was normal in all.
      Conclusions: This difference between biliary and parenchymal liver disease may have clinical implications, which need to be defined.

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