Imbalances between the levels of tissue factor and tissue factor pathway inhibitor in ARDS patients.
BACKGROUND
To evaluate the pathogenetic role of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and neutrophil elastase in acute respiratory distress syndrome (ARDS), as well as to test the hypothesis that TFPI levels modified by neutrophil activation are not sufficient to prevent TF-dependent intravascular coagulation, leading to sustained systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which determine the prognosis of these patients.


METHODS
The study subjects consisted of 55 patients with trauma and sepsis who were divided into three groups according to the Lung Injury Score. Ten normal healthy volunteers served as control. Plasma levels of TF, TFPI, and neutrophil elastase were measured on the day of injury or the day of diagnosis of sepsis (day 0) and days 1 through 4. The number of SIRS criteria that the patient met and the disseminated intravascular coagulation (DIC) score is determined daily.


RESULTS
Patients (15) developed ARDS, 23 were at risk for but did not develop the syndrome, and 17 patients were without risk for ARDS. TF and neutrophil elastase levels in ARDS patients were persistently higher than those in other two groups and control subjects. However, the TFPI levels showed no difference among the three groups, which retained normal or slightly elevated levels compared to the control subjects. DIC scores did not improve and SIRS continued during the study period in patients with ARDS. The ARDS patients showed higher numbers of dysfunctioning organs and associated with poorer outcome than the other two groups.


CONCLUSIONS
Systemic activation of the TF-dependent pathway not adequately balanced by TFPI is one of the aggravating factors of ARDS. High levels of neutrophil elastase released from activated neutrophils may explain the imbalance of TF and TFPI. Persistent DIC and sustained SIRS contribute to MODS, determining the prognosis of ARDS patients.
Gando
Satoshi
S
Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, N15, W7, Kita-ku, Sapporo, 060 Japan. sgando@med.hokudai.ac.jp
Kameue
Takashi
T
Matsuda
Naoyuki
N
Hayakawa
Mineji
M
Morimoto
Yuji
Y
Ishitani
Toshiteru
T
Kemmotsu
Osamu
O
D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood* / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism*; D018570:Risk Assessment / Q000379:methods; D013223:Statistics as Topic; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000378:metabolism; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*
D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D013925:Thromboplastin; D019272:Leukocyte Elastase