Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients

To evaluate the contribution of an imbalance between coagulation activation and fibinolysis activation and inhibition to morbidity and mortality in se psis, we determined in medical hospitalized patients at inclusion (day 0) f or fever temperature above 38.0 degrees C axillary or 38.3 degrees C rectal ly), and daily thereafter for two days, circulating thrombin-antithrombin I II (TAT) complexes, plasmin-alpha (2)-antiplasmin (PAP) complexes (day 0 on ly), tissue-type plasminogen activator (t-PA), plasminogen activator inhibi lor-1 (PAI-1) and interleukin (IL)-6, the latter as a marker of the inflamm atory host response. Study variables were 1) positive microbiological resul ts for specimens from local sites associated with a clinical infection, pos itive blood cultures (including parasitemia) or both, within 7 days after i nclusion, 2) development of shock, i.e. systolic blood pressure < 90 mmHg o r a reduction of 40 mmHg from baseline within 7 days after inclusion, and 3 ) death related to febrile illness within 28 days after inclusion. The peak plasma levels of TAT complexes were elevated in 44% and the PAP complexes in all patients. The t-PA and PAI-1 levels were elevated in 74 and 94% of p atients, respectively. Values for TAT and PAP did not differ among subgroup s, while peak t-PA and IL-6 levels were higher in patients with positive mi crobiological results, developing shock or ultimately dying than in those w ithout the complications (p <0.005). Peak PAI-1 levels were elevated in pat ients developing shock and ultimate death versus those with an uncomplicate d course (p <0.05). Peak IL-6 related to PAI-I and t-PA levels, which inter related. Patients with elevated TAT levels had increased plasma levels of I L-6, PAP, PAl-1 and t-PA versus those with normal TAT (p <0.05). Our data i ndicate that inhibition of activated fibrinolysis, which may partly depend on both cytokinemia and activation of coagulation, predicts microbial infec tion, septic shock and mortality of febrile medical patients. This suggests an early pathogenic role of inhibition of activated fibrinolysis in the do wnhill course of serious microbial infection.