'WE CANNOT SOLVE OUR PROBLEMS WITH THE SAME THINKING WE USED WHEN WE CREATED THEM.'Albert Einstein
> E X P L O R I N G G R A N U L A R I T Y I N P L AT E L E T R E S E A R C H 4 E X P L O R I N G G R A N U L A R I T Y I N P L AT E L E T R E S E A R C H
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TABLE OF CONTENTS CHAPTER 1Introduction 7 CHAPTER 2 Hypothermia: effects on platelet function and hemostasis 15CHAPTER 3 Response of platelet concentrates to pressure and temperature 27 changes without impairment of the in vitro function CHAPTER 4 Platelet function during hypothermia in experimental mock circulation 39CHAPTER 5 Early platelet recovery following cardiac surgery with cardiopulmonary 51 bypass CHAPTER 6 Thrombin generation and platelet activation in cytoreductive surgery 67 combined with hyperthermic intra-peritoneal chemotherapy CHAPTER 7 Normalization methods in time series of platelet function assays.91From sample to big data 117
CHAPTER 9 Discussion and valorization 145Nederlandse samenvatting 159
English summary 165Publications 171Biography 177Thanks and acknowledgements 181CHAPTER 8
E X P L O R I N G G R A N U L A R I T Y I N P L AT E L E T R E S E A R C H 6 E X P L O R I N G G R A N U L A R I T Y I N P L AT E L E T R E S E
BACKGROUNDFor computationally managing the various levels of detail in biomedical data, biological granularity is indispensable for both dealing effectively with large amounts of data and for structuring the knowledge to analyze and vertically integrate, across the different levels of granularity. Managing granularities of data in the field of platelet research requires specific methodologies to evolve to new knowledge applicable for clinical practice. In this thesis, the author attempted to find inflection points for innovation. Current inflection points in biomedical research are related with the capacity for description and collecting data, the efficiency of compiling, organizing, manipulating these data and extracting true understanding of fundamental biological processes, and insights into human health and disease, from them.
PLATELET BIOLOGYPlatelets (2~4 microns in diameter) are essential effectors of cellular hemostasis in humans and other mammals. Although the relevance of platelets in hemostasis and thrombosis is well established, platelets also contribute to host inflammatory and immune responses in infections or injury [1]. Suggested by comparative biology of the innate antibacterial and primitive hemostatic systems of invertebrates, the anucleate human platelet is a specialized cell fragment unique to mammals. Nonmammalian vertebrates, such as fish and birds, have nucleated platelets. Fig. 1.Invertebrates have an even more primitive blood cell, the amebocyte. The amebocyte is the single blood cell of invertebrates with a multitude of functions. The presence of platelets in fetal blood by 12 weeks of gestation suggests that platelet functions are useful to the fetus [2]. Platelets lack nuclei, but perform various vital functions of nucleated cells. Platelets can generate new cell bodies packed with respiring m...