Caleb Fisher1, Vishal C Patel2, Sidsel Hyldgaard Stoy3, Arjuna Singanayagam3, Jelle Adelmeijer4, Julia Wendon2, Debbie L Shawcross3, Ton Lisman4, William Bernal5. 1. Liver Intensive Care Unit, Institute of Liver Studies, King College Hospital, London, United Kingdom. Electronic address: Caleb.fisher@nhs.net. 2. Liver Intensive Care Unit, Institute of Liver Studies, King College Hospital, London, United Kingdom. 3. Institute of Liver Studies, Kings College Hospital, London, United Kingdom. 4. Surgical Research Laboratory, University Medical Center Groningen, Groningen, Netherlands. 5. Liver Intensive Care Unit, Institute of Liver Studies, King College Hospital, London, United Kingdom. Electronic address: william.bernal@kcl.ac.uk.
Abstract
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.
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.
Authors: Alberto Zanetto; Henry M Rinder; Elena Campello; Graziella Saggiorato; Yanhong Deng; Maria Ciarleglio; Francis P Wilson; Marco Senzolo; Sabrina Gavasso; Cristiana Bulato; Paolo Simioni; Guadalupe Garcia-Tsao Journal: Hepatology Date: 2020-10 Impact factor: 17.425
Authors: Ellen G Driever; R Todd Stravitz; Jingwen Zhang; Jelle Adelmeijer; Valerie Durkalski; William M Lee; Ton Lisman Journal: Hepatology Date: 2021-05 Impact factor: 17.425