A comparative study of the protein C pathway in septic and nonseptic patients with organ failure.
BACKGROUND
Severe sepsis is associated with an exacerbated procoagulant state with protein C (PC) system impairment. In contrast, the inflammatory and coagulation status of nonseptic patients with organ failure (OF) is less documented.


OBJECTIVE
To compare coagulation activation, focusing on the PC system, and inflammatory status in septic and nonseptic patients with OF.


METHODS
Thirty patients with severe sepsis and 30 nonseptic patients were recruited at the onset of OF and compared with 30 matched healthy subjects. We performed an extensive analysis of the PC pathway, including plasma protein measurements and quantification of leukocyte expression of PC system receptors. In addition, we analyzed the inflammatory status, based on inflammation-related gene leukocyte expression.


RESULTS
We observed coagulation activation, reflected by a similar increase in tissue factor mRNA expression, in the two patient groups when compared with the healthy subjects. Soluble thrombomodulin levels were higher in septic patients than in healthy control subjects, whereas PC, protein S, and soluble endothelial cell PC receptor levels were lower. Similar results were obtained in nonseptic patients with OF. Monocyte thrombomodulin overexpression, together with increased circulating levels of activated PC, suggests that the capacity for PC activation is at least partly preserved in both settings. No difference in the inflammatory profile was found between septic and nonseptic patients.


CONCLUSIONS
The pathogenesis of OF in critical care patients is characterized by an overwhelming systemic inflammatory response and by exacerbated coagulation activation, independently of whether or not infection is the triggering event. Clinical trial registered with www.clinicaltrials.gov (NCT 00361725).
INSERM Unité 765, Paris, France.
Delphine
D
Borgel
Caroline
C
Bornstain
Pieter H
PH
Reitsma
Nicolas
N
Lerolle
Sophie
S
Gandrille
Fouad
F
Dali-Ali
Charles T
CT
Esmon
Jean-Yves
JY
Fagon
Martine
M
Aiach
Jean-Luc
JL
Diehl
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D001777:Blood Coagulation / Q000502:physiology*; D016022:Case-Control Studies; D000074283:Endothelial Protein C Receptor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000150:complications; D011486:Protein C / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics; D018805:Sepsis / Q000097:blood* / Q000150:complications; D018180:Thrombomodulin / Q000097:blood / Q000235:genetics; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D017293:Protein S; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; D013925:Thromboplastin