New insights into haemostasis in liver failure.
The precise mechanisms leading to the coagulopathy of acute liver injury are unclear. To study this further, coagulation and immune changes have been compared in patients with acute liver injury secondary to paracetamol overdose, with chronic cirrhosis, and normal healthy controls. In acute liver injury, coagulation factors II, V, VII and X were reduced to a similar degree, and were significantly lower than factors IX and XI. In cirrhosis, by contrast, these coagulation factors were reduced to similar levels. Factor VIII increased in acute liver injury, but was normal in cirrhosis. Interleukin-6 and tumour necrosis factor-alpha levels increased in both patient groups, but were higher in paracetamol overdose. Thrombin-antithrombin and soluble tissue factor levels increased in those with acute liver injury, but were normal in patients with cirrhosis. Functional antithrombin was reduced in both acute liver injury and cirrhosis. It is hypothesized that in acute paracetamol-induced liver injury, immune activation leads to tissue factor-initiated consumption of factors II, V, VII and X, but that levels of factors IX and XI are better preserved because of inhibition of the thrombin-induced amplification phase of coagulation. These findings have implications for appropriate coagulation factor support for patients with acute liver injury.
Kerr
Ron
R
Department of Haematology, Royal Infirmary of Edinburgh, Edinburgh, UK. ron.kerr@ed.ac.uk
D000082:Acetaminophen / Q000009:adverse effects; D000208:Acute Disease; D000991:Antithrombins / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000276:immunology; D001779:Blood Coagulation Factors / Q000032:analysis / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000097:blood; D062787:Drug Overdose; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications; D017093:Liver Failure / Q000150:complications*
D000991:Antithrombins; D001779:Blood Coagulation Factors; D016207:Cytokines; D000082:Acetaminophen