Coagulation/fibrinolysis balance in septic shock related to cytokines and clinical state.
This study explored the relationship between cytokines (TNF, IL-1, IL-6), coagulation and fibrinolytic factors in the early stage of sepsis syndrome and the relation between these factors with the severity of inflammatory illness as measured by the Simplified Acute Physiology Score (SAPS). Twenty-one normal controls were compared to 34 patients divided into three categories ranging from uncomplicated postoperative patients, to patients with severe infectious conditions including septic shock. A major hemostatic imbalance was demonstrated with particularly marked reduction in fibrinolytic activity [drop of antithrombin III (ATIII) and protein C with an increase of plasminogen activator inhibitor (PAI-1) levels] which were directly correlated with the severity of the inflammatory state. Both ATIII and PAI-1 levels were correlated with the levels of TNF and IL-6 and the severity of illness as measured by SAPS. We established an index, ATIII/PAI-1 antigen that is significantly different among the four groups (p < 0.001) and strongly correlated with the SAPS (p < 0.001). As PAI-1 could be secreted not only by TNF activating endothelial cells but also by hepatocytes activated by insulinemia, treatment of sepsis with cytokine-specific agents might be of limited effect.
Faculté de Médecine Lyon-Nord, Pierre-Bénite, France.
D
D
Massignon
A
A
Lepape
J
J
Bienvenu
Y
Y
Barbier
C
C
Boileau
P
P
Coeur
D000328:Adult; D000368:Aged; D001427:Bacterial Toxins / Q000494:pharmacology; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis; D001780:Blood Coagulation Tests; D001798:Blood Proteins / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001427:Bacterial Toxins; D001779:Blood Coagulation Factors; D001798:Blood Proteins; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha