Sarah Bos

31 Hemostatic profiles are similar across all etiologies of cirrhosis. 2 For secondary hemostasis testing our results of thrombin generation adds to growing literature showing that patients with cirrhosis have enhanced thrombin generating capacity when tested with assays that take plasma levels of many pro- and anticoagulant drivers into account (i.e., thrombomodulin-modified thrombin generation testing).(6,29–31) There appear to be subtle differences in thrombin generation capacity between etiologies of cirrhosis that are not explained by differences in the levels of pro- and anticoagulant proteins that we have measured. It may be that plasma factors other than the known pro- or anticoagulant proteins are responsible for these differences. In contrast to the seminal paper by Tripodi et al. published in 2005,(7) who reported normal thrombin generation in patients with cirrhosis, it appears firmly established that patients with CTP A to critically ill patients are in fact characterized by enhanced thrombin generating capacity. These results stress that patients are not ‘auto-anticoagulated’ as suggested by their prothrombin time, and should encourage studies on optimal treatment modalities for prevention and treatment of thrombotic events in patients with cirrhosis.(32) Interestingly, although the PT was prolonged in all etiologies, the aPTT was only prolonged in cholestatic disease and in viral hepatitis. These differences are not readily explained by plasma levels of individual coagulation factors, which were similarly decreased across etiologies. Even more, the cholestatic group had the highest levels of FVIII, which is an important determinant of the APTT, but paradoxically had the highest prolongation of the test. The prolonged APTT in the cholestatic group may therefore be related to the presence of an inhibitor, which may be related to the autoimmune component of cholestatic disease. Lupus anticoagulant activity, which is known to prolong the APTT, but is paradoxically also significantly associated with venous thrombosis(33,34), has been reported with high frequency in patients with cirrhosis.(33,34) Whether there is a difference between etiologies is not reported. Future studies should assess the role of such antibodies in prolongation of the APTT, and with thrombotic events in patients with cirrhosis. Our analyses for fibrinolysis consisted of clot lysis time and clot density measurement together with fibrinogen levels. The prothrombotic nature of our in vitro generated fibrin clots is also in line with previous work. However, in the present cohort of patients with mild disease, plasma levels of fibrinogen were elevated compared to controls. Therefore, the elevated fibrinogen levels per se, rather than intrinsic changes in the fibrinogen molecule as we have previously reported, could explain the increase in fibrin clot thrombogenicity.