Decreased protein C activation in patients with fulminant hepatic failure.
OBJECTIVE
Abnormalities of the blood coagulation system have an influence on outcome in patients with fulminant hepatic failure (FHF). The protein C (PC) pathway is one of the main modulators of the blood coagulation system. The role of the PC pathway in FHF is not clear. In the present study, we evaluated endothelial cell injury and the grade of activated protein C (APC) generation in FHF patients.


METHODS
The effect of APC on the expression of tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 from LI90 stellate cells was also evaluated. This study comprised 5 patients with FHF, 6 with acute hepatitis (AH), 12 with chronic hepatitis (CH) and 20 healthy subjects.


RESULTS
The plasma concentrations of thrombin-antithrombin complex and thrombomodulin were significantly increased in FHF patients compared with those in AH patients and healthy subjects. The circulating levels of activated protein C-protein C inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were significantly decreased in patients with FHF compared to healthy controls. APC significantly inhibited in vitro the expression of TNFalpha and MCP-1 from LI90 stellate cells.


CONCLUSIONS
This study demonstrated enhanced endothelial cell injury in association with decreased PC activation and hypercoagulability in FHF.
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Division of Pulmonary and Critical Care Medicine, Mie University School of Medicine, Edobashi, Tsu-city, Japan.
Michihiko
M
Yamaguchi
Esteban C
EC
Gabazza
Osamu
O
Taguchi
Yutaka
Y
Yano
Jiro
J
Ikoma
Masahiko
M
Kaito
Yuji
Y
Kojima
Ichiro
I
Imoto
Akitoshi
A
Satomi
Corina N
CN
D'Alessandro-Gabazza
Tatsuya
T
Hayashi
Hisataka
H
Moriwaki
Koji
K
Suzuki
Yukihiko
Y
Adachi
D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D017114:Liver Failure, Acute / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D011486:Protein C / Q000378:metabolism*; D018046:Protein C Inhibitor / Q000097:blood; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D011486:Protein C; D018046:Protein C Inhibitor; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D012313:RNA; D000990:Antithrombin III; D010447:Peptide Hydrolases