Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation.
BACKGROUND
For systematic elucidation of serial changes in neutrophil-endothelial activation markers as well as to investigate the correlationship among the inflammation markers, disseminated intravascular coagulation (DIC), and multiple organ dysfunction syndrome (MODS) in patients with sepsis, we made this prospective study.


METHODS
Forty-five patients with sepsis, severe sepsis, and septic shock were subdivided into two groups, 27 with DIC and 18 without DIC. Eight normal healthy volunteers served as control subjects. Serial levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 12 h after the diagnosis of sepsis (day 0) and on days 1-4 after the diagnosis. The numbers of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined simultaneously.


RESULTS
Acute Physiology and Chronic Health Evaluation (APACHE) II score was identical between the two groups. In the DIC patients, higher DIC scores, lower platelet counts, and more maximum numbers of SIRS criteria being met were observed compared with the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the patients with DIC than those without DIC, and the DIC patients had poor outcome. Soluble L-selectin (sL-selectin) levels in both groups tended to be lower than those in the control subjects. All other parameters both in the two groups were continuously higher than those in the control subjects during study period. The levels of soluble E-selectin (sE-selectin), sICAM-1, sVCAM-1, neutrophil elastase, and sTM were more elevated in the DIC patients than those in the non-DIC patients. There were no differences in the sP-selectin levels between the two groups; however, more increased sP-selectin levels per platelet were found in the DIC patients compared with the non-DIC patients. Maximum DIC scores in the DIC group positively correlated with the peak levels of neutrophil elastase and sTM and the number of the dysfunctioning organs.


CONCLUSIONS
We found close relations among the neutrophil-endothelial cell interactions, DIC, and MODS in patients with sepsis, severe sepsis, and septic shock. The results indirectly confirm the concept that DIC can produce organ dysfunction and that DIC reflects an inflammatory disorder of the microvasculature.
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. gando@med.hokudai.ac.jp
Kameue
Takashi
T
Matsuda
Naoyuki
N
Hayakawa
Mineji
M
Hoshino
Hirokatsu
H
Kato
Hirokatsu
H
D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis / Q000209:etiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology; D005260:Female; D006801:Humans; D007249:Inflammation; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000209:etiology; D009504:Neutrophils / Q000166:cytology* / Q000502:physiology; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood / Q000150:complications* / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome; D018180:Thrombomodulin / Q000032:analysis
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018180:Thrombomodulin; D019272:Leukocyte Elastase