The activation of neutrophil elastase-mediated fibrinolysis is not sufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation associated with systemic inflammation.

INTRODUCTION: We conducted a prospective study to test the hypothesis that the activation of neutrophil elastase-mediated fibrinolysis is insufficient to overcome the fibrinolytic shutdown of disseminated intravascular coagulation (DIC) in patients associated with systemic inflammation.

MATERIALS AND METHODS: We investigated 45 consecutive patients with systemic inflammatory response syndrome (SIRS) and sepsis, classified as 11 DIC and 34 non-DIC. Fibrin degradation products by neutrophil elastase (Elastase-XDP) and by plasmin (FDP), cross-linked fibrin degradation products (D-dimer), soluble fibrin, antithrombin, protein C, plasminogen activator inhibitor-1 (PAI-1), and urinary trypsin inhibitor (UTI) were measured within 24 h after the patients met either the SIRS or sepsis criteria (day 0), as well as on days 2 and 4.

RESULTS: In DIC patients, higher levels of soluble fibrin, PAI-1, and FDP and markedly lower levels of antithrombin and protein C were observed in comparison to those in non-DIC patients. DIC patients showed a significantly higher level of peak Elastase-XDP than non-DIC patients (25.7+/-5.9 vs. 16.3+/-2.6 microg/mL, respectively; p=0.0333). However, we could not find any substantial difference in the levels of Elastase-XDP, UTI, and D-dimer on each day during the study period between the two groups. Good correlations were observed between the levels of D-dimer and Elastase-XDP in both patients with and without DIC (r(s)=0.699 and r(s)=0.817, respectively), but the coefficients of determination in both groups showed low values and the slopes of the regression lines were less than 1.0. A multivariate logistic regression analysis showed the elevated peak Elastase-XDP levels to inversely correlate with death. On the other hand, the DIC patients showed a higher number of organ dysfunctions and a poorer prognosis than did the non-DIC patients.

CONCLUSIONS: The activation of the neutrophil elastase-mediated fibrinolytic pathway may be insufficient to overcome the fibrinolytic shutdown by PAI-1 and may in part explain the poor prognosis of DIC patients associated with systemic inflammation.