• Satoshi Gando, Mineji Hayakawa, Atsushi Sawamura, Hirokatsu Hoshino, Akiko Oshiro, Nobuhiko Kubota, and Subrina Jesmin.
• Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N17 W5, Kita-ku, Sapporo 060 Japan. gando@med.hokudai.ac.jp
• Thromb. Res. 2007 Jan 1;121(1):67-73.

IntroductionWe 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 MethodsWe 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.ResultsIn 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.ConclusionsThe 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.

19 keywords...

hide…