- Author
- Title
- The protein C system in severe infection
- Supervisors
- Co-supervisors
-
C. van 't Veer
- Award date
- 14 March 2014
- Number of pages
- 305
- ISBN
- 9789090281155
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
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.
- Note
- Research conducted at: Universiteit van Amsterdam
- Persistent Identifier
- https://hdl.handle.net/11245/1.412716
- Downloads
-
Cover
Title pages
Contents
1: General introduction and outline of the thesis
2: Inflammation, endothelium and coagulation in sepsis
3: The cytoprotective effects of endogenous activated protein C contribute to inhibition of coagulation during murine pneumococcal pneumonia and sepsis
4: Impact of endogenous protein C on pulmonary coagulation and injury during lethal H1N1 influenza in mice
5: Endogenous protein C inhibits activation of coagulation and transiently lowers bacterial outgrowth in murine Escherichia coli peritonitis
6: The endothelial protein C receptor impairs the antibacterial response in murine pneumococcal pneumonia and sepsis
7: Protease-activated receptor-1 impairs host defense in murine pneumococcal pneumonia
9: Effect of the factor V Leiden mutation on the incidence and outcome of severe infection and sepsis
10: Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia
12: Therapeutic recombinant murine activated protein C attenuates pulmonary coagulopathy and improves survival in murine pneumococcal pneumonia
13: Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia
14: Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza
15: Summary and general discussion
Nederlandse samenvatting
List of publications
PhD portfolio
Dankwoord
About the author
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