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

J Crit Care. 2018 Feb:43:54-60. doi: 10.1016/j.jcrc.2017.07.053. Epub 2017 Aug 17.

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.

Keywords: Acute-on-chronic liver failure; Cirrhosis; Coagulation critically ill; Thrombin generation.

Publication types

  • Observational Study

MeSH terms

  • Acute-On-Chronic Liver Failure / drug therapy
  • Acute-On-Chronic Liver Failure / metabolism
  • Acute-On-Chronic Liver Failure / physiopathology*
  • Adult
  • Aged
  • Blood Coagulation
  • Blood Coagulation Tests
  • Critical Illness* / therapy
  • Disease Progression
  • Factor VIII / metabolism
  • Female
  • Fibrinolysis
  • Hemostasis*
  • Hemostatics
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Thrombin / metabolism
  • Thrombomodulin / metabolism

Substances

  • Hemostatics
  • THBD protein, human
  • Thrombomodulin
  • F8 protein, human
  • Factor VIII
  • Thrombin