Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock.
OBJECTIVE
To determine whether the fibrinolytic system is activated and coagulation inhibitors are utilized in sepsis, to compare the findings detected in sepsis with those found in severe sepsis and septic shock, and to compare the role played by different infectious pathogens on fibrinolysis and coagulation inhibitors.


METHODS
Prospective study comparing patients with sepsis, severe sepsis, and septic shock and healthy volunteers in the general intensive care unit of a tertiary university hospital.


METHODS
Eighty-two consecutive septic patients (47 with sepsis, 18 with severe sepsis, and 17 with septic shock), and 14 healthy volunteers (controls).


RESULTS
After blood sampling we measured activation markers of fibrinolysis [plasmin/alpha(2)-antiplasmin complexes (PAP), complexes of tissue plasminogen activator/plasminogen activator inhibitor (tPA/PAI), fibrin(ogen) degradation products (FDPs), D-dimmers fibrin degradation products (D-d)], the utilization marker of antithrombin III (ATIII) thrombin/antithrombin complexes (TAT), several factors of fibrinolysis [plasminogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), alpha(2)-antiplasmin], and the natural coagulation inhibitors [ATIII, protein C (PrC), protein S (PrS)]. In sepsis, PAP, FDPs, D-d, and TAT were increased to 439.8+/-32.35 microg/l, 57% positive, 49% positive, and 3.46+/-0.27 microg/l, respectively, compared with control subjects (205.57+/-28.58 microg/l, 0% positive, 7% positive, and 1.61+/-0.1 microg/l, respectively). These markers further increased in severe sepsis and septic shock. With the exception of a decrease in ATIII and an increase in tPA and PAI-1, coagulation inhibitors and factors of fibrinolysis were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation inhibitors (ATIII, PrC) and plasminogen were markedly decreased, whereas tPA and PAI-1 were further increased. All changes were independent of the causative infectious pathogen.


CONCLUSIONS
Fibrinolysis is strongly activated and ATIII is utilized in sepsis. These findings are further enhanced in severe sepsis and septic shock. In sepsis only ATIII is decreased. In contrast, in severe sepsis and mainly in septic shock plasminogen and the main coagulation inhibitors (i.e., ATIII, PrC) are depleted, indicating exhaustion of fibrinolysis and coagulation inhibitors. Finally, Gram-positive, Gram-negative and other micro-organisms produce identical impairment.
Mavrommatis
A C
AC
Department of Critical Care, General Hospital of Nikea, 3 Mandouvalou D. St., 18454 Piraeus, Greece. a_mavrommatis@yahoo.com
Theodoridis
T
T
Economou
M
M
Kotanidou
A
A
El Ali
M
M
Christopoulou-Kokkinou
V
V
Zakynthinos
S G
SG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005342:Fibrinolysis / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000276:immunology; D012772:Shock, Septic / Q000097:blood* / Q000276:immunology
D015415:Biomarkers; D019774:Blood Coagulation Factor Inhibitors