title: Effects of acute liver injury on blood coagulation.
abstract: The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL(-1), respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL-1, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL(-1), respectively). Interleukin-6 and tumor necrosis factor-alpha levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.
authors.affiliation: Department of Haematology and Department of Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK. Ron.Kerr@ed.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Kerr
authors.forename: P
authors.initials: P
authors.lastname: Newsome
authors.forename: L
authors.initials: L
authors.lastname: Germain
authors.forename: E
authors.initials: E
authors.lastname: Thomson
authors.forename: P
authors.initials: P
authors.lastname: Dawson
authors.forename: D
authors.initials: D
authors.lastname: Stirling
authors.forename: C A
authors.initials: CA
authors.lastname: Ludlam
mesh_terms: D000082:Acetaminophen; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000032:analysis; D016022:Case-Control Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood; D017114:Liver Failure, Acute / Q000097:blood* / Q000139:chemically induced; D008875:Middle Aged; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000097:blood; D013925:Thromboplastin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D001779:Blood Coagulation Factors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D000082:Acetaminophen; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases