Balanced haemostasis with both hypo- and hyper-coagulable features in critically ill patients with acute-on-chronic-liver failure

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Background:Cirrhotic patients have complex haemostatic abnormalities. Current evidence suggests stable cirrhotic (SC) patients have a “re-balanced” haemostatic state. However, limited data exists in acute decompensated (AD) or acute on chronic liver failure (ACLF) patients.Methods:We utilised thrombin generation analysis, fibrinolysis assessment, and evaluation of haemostatic parameters to assess haemostasis in liver disease of progressive severity.Results:The study cohorts were comprised of: SC, n = 8; AD n = 44; ACLF, n = 17; and Healthy Control (HC), n = 35. There was a progressive increase across the cohorts in INR (p = 0.0001), Factor VIII (p = 0.0001) and VWF levels (p = 0.0001) and a correspondingly decrease in anti-thrombin (p = 0.0001), ADAMTS-13 (p = 0.01) and fibrinogen levels (p = 0.0001). In the presence of thrombomodulin, thrombin generation was equivalent or significantly higher in all the cohorts compared to HC (p = 0.0001). Compared to AD, ACLF had a lower ETP (p = 0.002) and thrombin peak (p = 0.0001). There was no significant difference across the cohorts in clot lysis time (p = 0.07), although compared to HC, AD had a significantly shorter lysis time (p = 0.001).Conclusions:Our cohorts, despite significant differences in haemostatic parameters, displayed intact thrombin generation but progressive hypo-functional clot stability and potentially but not universal hyper-functional haemostasis.Highlights:Haemostatic parameters change progressively from stable cirrhosis to acute-on-chronic liver failure.Thrombin generation remains intact in acute decompensated and acute-on-chronic liver failure.Clot stability varied significantly between the cohorts.Acute-on-chronic liver failure appears to have a separate haemostatic phenotype.

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