TAFI and PAI-1 levels in human sepsis.
BACKGROUND
Plasminogen activator inhibitor type-1 (PAI-1) is considered to be the main inhibitor of fibrinolysis in sepsis. However, the contribution of TAFI to the inhibition of fibrinolysis in sepsis is currently unknown.


METHODS
TAFI antigen and PAI-1 levels were measured in severe sepsis (n = 32) and septic shock (n = 8) patients. In addition, TAFI antigen levels had been determined in 151 controls.


RESULTS
Septic patients had significantly (p < 0.0001) decreased TAFI levels (median: 78.9% [range: 32.4-172.6]) as compared to controls (108.1% [35.9-255.4]). TAFI levels were equal in septic shock and severe sepsis (68.9% [32.4-172.6] vs. 82.5% [32.7-144.9], p = 0.987) as well as in survivors and non-survivors (87.1% [32.7-172.6] vs. 65.8% [32.4-129.5], p = 0.166). PAI-1 levels were significantly (705.5 ng/ml [131-5788]) higher in septic shock as in severe sepsis patients (316.5 ng/ml [53-1311], p = 0.016) and were equal in survivors and non-survivors (342 ng/ml [53-1311] vs. 413 ng/ml [55-5788], p = 0.231). TAT/PAP ratio (R((TAT/PAP))) reflecting the dysbalance between coagulation and fibrinolysis was calculated. R((TAT/PAP)) significantly increased with fatality and was significantly dependent on PAI-1, but not on TAFI. PAI-1 levels (570.5 ng/ml [135-5788]) and R((TAT/PAP)) (1.6 [0.3-6.1]) were significantly (p = 0.008 and p = 0.047) higher in patients with overt DIC as compared to patients without overt DIC (310 ng/ml [53-1128] and 0.6 [0.1-4.3]), whereas no difference was found for TAFI levels (68.9% [32.7-133.2] vs. 86.4% [32.4-172.6], p = 0.325).


CONCLUSIONS
Although inhibition in sepsis is mediated by both, PAI-1 might be involved early in the sepsis process, whereas TAFI might be responsible for ongoing fibrinolysis inhibition in later stages of sepsis.
Zeerleder
Sacha
S
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern, Switzerland. s.zeerleder@sanquin.nl
Schroeder
Verena
V
Hack
C Erik
CE
Kohler
Hans Peter
HP
Wuillemin
Walter A
WA
D000328:Adult; D000368:Aged; D025901:Carboxypeptidase B2 / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000503:physiopathology; D000073718:Pancreatitis-Associated Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000401:mortality
D000073718:Pancreatitis-Associated Proteins; D017395:Plasminogen Activator Inhibitor 1; C000612141:REG3A protein, human; D025901:Carboxypeptidase B2