Activation of the fibrinolytic system in patients with fulminant liver failure.
Abnormalities of blood coagulation and fibrinolysis are a major part of fulminant liver failure. In this study, the key components of the fibrinolytic system were determined in 42 patients with this condition. Admission levels of plasma plasminogen activity were low (9.1% of normal), as to a lesser extent were the activities of its inhibitors alpha 2-antiplasmin (20.5% of normal) and C1 inhibitor (64% of normal). Tissue plasminogen activator activity was found at normal levels, whereas the level of its fast inhibitor, plasminogen activator inhibitor-1, was greatly increased compared with that of controls (24.3 U/ml and 7.4 U/ml, respectively), indicating a shift toward inhibition of fibrinolysis in these patients. Thrombin-antithrombin complex levels in plasma were significantly increased in fulminant liver failure compared with those in controls (33.5 micrograms/L vs. 2.5 micrograms/L, p < 0.001), indicating activation of coagulation in these patients. High plasma levels of D-dimer, a fragment of cross-linked fibrin, were also found (1,510 micrograms/L vs. 33 micrograms/L in controls, p < 0.001); this finding correlated with the increased level of thrombin-antithrombin complex (r = 0.61, p < 0.001), consistent with activation of fibrinolysis resulting from intravascular coagulation. In conclusion, there are gross abnormalities of the fibrinolytic system in fulminant liver failure, but because inhibitory activity appears to be present in adequate quantities, this limits the incidence of bleeding due to fibrinolysis.
Pernambuco
J R
JR
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Langley
P G
PG
Hughes
R D
RD
Izumi
S
S
Williams
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000172:deficiency; D004211:Disseminated Intravascular Coagulation / Q000209:etiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D006470:Hemorrhage / Q000209:etiology; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D010958:Plasminogen / Q000172:deficiency; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000172:deficiency
D003174:Complement C1 Inactivator Proteins; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D010958:Plasminogen; D010447:Peptide Hydrolases