- The protein C system in severe infection
T. van der Poll
C. van 't Veer
- Award date
- 14 March 2014
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
There is ample evidence on the crosstalk between coagulation and inflammation. However, many questions remain in this fascinating area in the setting of severe infectious disease. In this thesis different studies on the endogenous PC system and, to a lesser extent, on rm-PAC and FVL in experimental infection were described. Our studies are consistent in showing that endogenous PC in various models and at various time points lowers activation of coagulation as it does in the normal, uninfected situation. Moreover we have been able to show in different models that endogenous PC lowers PAI-1 levels in severe infection, hereby potentially facilitating fibrinolysis. The studies presented in this thesis indicate that different components of the PC system impact on host defense in different ways. From our studies it becomes clear that in severe infectious disease, much of the functioning of the endogenous PC system still is incompletely understood. Also, phenotypes can be changed to a large extent when the effect of a protein or receptor is studied in infection with concomitant antibiotic treatment. Also, from our rm-APC studies we can learn that timing of interventions is important. Our studies should be interpreted with caution upon extrapolation to human sepsis, since sepsis patients suffer from different microbes, from different first affected organs and in different phases of their disease. We suggest that more research has to be done to enable better classification and stratification of critically ill patients that are now simply and perhaps incorrectly denominated as patients suffering from severe sepsis.
- Research conducted at: Universiteit van Amsterdam
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