Coagulation system and platelets are fully activated in uncomplicated sepsis.
OBJECTIVE
To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock.


METHODS
Prospective study comparing patients with sepsis, severe sepsis, and septic shock, and healthy volunteers.


METHODS
General intensive care unit in a tertiary university hospital.


METHODS
Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers served as control subjects.


METHODS
None.


RESULTS
After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (beta-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin were increased to 2.52+/-0.21 nmol/L, 20.88+/-2.52 ng/mL, 33.8+/-2.9 microg/L, and 69% positive, respectively, compared with control subjects (0.86+/-063 nmol/L, 1.14+/-0.15 ng/mL, 16.07+/-1.01 microg/L, and 0%, respectively). Beta-Thromboglobulin and the beta-thromboglobulin-to-platelet factor 4 ratio were also increased to 107.87+/-11.87 IU/mL and 8.86+/-1.06, compared with controls (18.36 +/-2.99 IU/mL and 2.67+/-0.52, respectively). With the exception of a decrease in factor XII and an increase in fibrinogen, coagulation factors, global coagulation tests, and PTL were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causative infectious pathogen.


CONCLUSIONS
Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.
Mavrommatis
A C
AC
Department of Critical Care and Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Greece.
Theodoridis
T
T
Orfanidou
A
A
Roussos
C
C
Christopoulou-Kokkinou
V
V
Zakynthinos
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000382:microbiology*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D005260:Female; D005344:Fibrinopeptide A / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D015539:Platelet Activation; D010976:Platelet Count; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000150:complications* / Q000382:microbiology; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000150:complications* / Q000382:microbiology
D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases