Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis.
OBJECTIVE
To determine the precise relationship among tissue factor, tissue factor pathway inhibitor (TFPI), and neutrophil elastase in sepsis, as well as to test the hypothesis that low TFPI concentrations are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome and death.


METHODS
Prospective, cohort study.


METHODS
General intensive care unit of tertiary care emergency department.


METHODS
Thirty-one consecutive patients with sepsis, classified as 15 survivors and 16 nonsurvivors. Ten normal, healthy volunteers served as controls.


METHODS
None.


RESULTS
Tissue factor antigen concentration (tissue factor), TFPI, neutrophil elastase, and global variables of coagulation and fibrinolysis were measured on the day of diagnosis of sepsis, severe sepsis, and septic shock and days on 1-4 after diagnosis. The number of systemic inflammatory response syndrome criteria that patients met and the disseminated intravascular coagulation score were determined simultaneously. The results of these measurements were compared between the survivors and the nonsurvivors. In the nonsurvivors, significantly higher concentrations of tissue factor and neutrophil elastase were found compared with the survivors and control subjects. However, the TFPI values showed no difference between the two groups. No correlation was found between the peak concentrations of tissue factor and TFPI. Disseminated intravascular coagulation scores and numbers of the SIRS criteria met by the survivors significantly decreased from day 0 to day 4, but those of the nonsurvivors did not improve during the study period. The nonsurvivors showed thrombocytopenia and higher numbers of dysfunctioning organs than did the survivors.


CONCLUSIONS
We systematically elucidated the relationship between tissue factor and TFPI in patients with sepsis, severe sepsis, and septic shock. Activation of tissue factor-dependent coagulation pathway not adequately balanced by TFPI has important roles in sustaining DIC and systemic inflammatory response syndrome, and it contributes to multiple organ dysfunction syndrome and death. High concentrations of neutrophil elastase released from activated neutrophils may explain, in part, the imbalance of tissue factor and TFPI in sepsis.
Gando
Satoshi
S
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Kameue
Takashi
T
Morimoto
Yuji
Y
Matsuda
Naoyuki
N
Hayakawa
Mineji
M
Kemmotsu
Osamu
O
D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D015331:Cohort Studies; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D019272:Leukocyte Elastase / Q000187:drug effects; D008074:Lipoproteins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D010976:Platelet Count; D011379:Prognosis; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D018805:Sepsis / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis; D013925:Thromboplastin / Q000096:biosynthesis* / Q000187:drug effects*; D016896:Treatment Outcome
D000925:Anticoagulants; D008074:Lipoproteins; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D019272:Leukocyte Elastase