Thrombin-antithrombin III complex in fulminant hepatic failure: evidence for disseminated intravascular coagulation and relationship to outcome.
Indirect evidence has suggested that intravascular coagulation may occur in patients with fulminant hepatic failure (FHF), the most severe form of acute liver disease. Thrombin is inhibited in circulation by antithrombin III, and measurement of the thrombin-antithrombin III complex (TAT) is a direct measure of thrombin formation. Using a new rapid enzyme-linked immunosorbent assay we have measured TAT in 54 patients on admission, with fulminant hepatic failure. TAT was significantly increased in patients with FHF compared with control subjects (25.8 +/- 2.7 micrograms l-1) compared with 2.6 +/- 0.2 micrograms l-1; n = 10: P less than 0.001). Patients who survived had significantly lower TAT levels than those who did not (17.2 +/- 2.7 micrograms l-1; n = 27 compared with 34.0 +/- 4.2 micrograms l-1; n = 27: P less than 0.005) and patients with FHF caused by viral hepatitis had significantly lower TAT levels than those with FHF due to paracetamol overdose (14.6 +/- 4.7 micrograms l-1; n = 9 compared with 28.0 +/- 3.1 micrograms l-1; n = 45: P less than 0.05). Levels of TAT correlated significantly with prothrombin time (r = 0.36, P less than 0.01) and inversely with fibrinogen (r = -0.51, P less than 0.001). There was no significant correlation with antithrombin III concentration. Thus, using a simple and rapid technique, we have been able to demonstrate increased levels of TAT complex in patients with FHF. This provides more direct evidence of intravascular coagulation and thrombin generation in these patients. These results confirm that the coagulation system is activated in FHF.
Langley
P G
PG
Liver Unit, King's College Hospital and School of Medicine and Dentistry, London, UK.
Forbes
A
A
Hughes
R D
RD
Williams
R
R
D000082:Acetaminophen / Q000506:poisoning; D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000150:complications; D062787:Drug Overdose / Q000150:complications; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000150:complications / Q000209:etiology; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D011379:Prognosis; D006435:Renal Dialysis / Q000009:adverse effects
C046193:antithrombin III-protease complex; D000082:Acetaminophen; D000990:Antithrombin III; D010447:Peptide Hydrolases