Activated protein C–protein C inhibitor complex as a prognostic marker in sepsis
© Heslet et al; licensee BioMed Central Ltd. 2008
Published: 18 November 2008
The PROWESS study and later trials of activated protein C (APC) treatment in sepsis have shown only modest reductions in mortality. A recent Cochrane systematic review (CD004388) records doubtful efficacy and serious adverse effects. To optimize the benefit/risk ratio of APC treatment of each patient, a biomarker of protein C (PC) activation is urgently needed and the use of such a marker, activated protein C–protein C inhibitor (APC–PCI), has been investigated in the present study.
APC–PCI was measured in acid citrate plasma by means of a newly developed sandwich ELISA (median normal value 0.13 ng/ml, range 0.07 to 0.26, n = 16). Levels of APC–PCI and PC were monitored (daily to alternate days) in 135 consecutive critically ill patients, 53 of whom had sepsis during the observation period. The state of PC activation to APC was categorized as nonactivated, moderately activated or highly activated, based on maximum APC–PCI values in relation to the normal range.
Mortality and relative mortality (mortality of activation group/overall mortality) of each activation group
PC activation group
Nonactivated, APC–PCI < 0.25 ng/ml
Moderately activated, APC–PCI 0.25 to 0.72 ng/ml
Highly activated, APC–PCI > 0.72 ng/ml
P value (χ2)
Sepsis mortality (deaths/n)
Nonactivation of PC in sepsis may represent the failure of an appropriate protective response and is therefore associated with increased mortality, especially when the APACHE II score is elevated. Septic patients without PC activation and a high APACHE II score may be those who are most likely to benefit from APC treatment. PC measurements were not predictive of PC activation as indicated by APC–PCI levels.
This article is published under license to BioMed Central Ltd.