- Author
-
D.J.B. Kleinveld
- Title
- Novel treatments for trauma-induced bleeding and organ failure
- Supervisors
- Award date
- 30 September 2021
- Number of pages
- 253
- ISBN
- 9789464166972
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Trauma remains one of the leading causes of morbidity and mortality in the adolescent life. During the early phase, trauma patients die from bleeding and brain injury. Later in trauma, when patients survive their initial bleeding phase, they are prone to develop organ failure. Trauma-induced bleeding, tissue injury and shock are accompanied by a clotting disorder referred to as trauma-induced coagulopathy (TIC). TIC consists of complex interplay between the (innate) immune system, endothelial cell activation, platelets dysfunction, coagulation factors consumption and (hyper)fibrinolysis. Together, these components result in an inadequate clot formation.
Resuscitation during the bleeding phase should be focused towards early tranexamic acid administration, limit crystalloid infusion, balanced transfusion component strategies and potentially even personalized correction of TIC using visco-elastic coagulation tests. During Intensive Care stay, TIC transfers towards a more hypercoagulable profile, associated with thrombo-embolic complications and organ failure. Protection of the endothelium during resuscitation could limit this hypercoagulable profile, thereby reducing organ failure during Intensive Care stay.
This thesis addresses several strategies to improve platelet transfusions during the resuscitation of trauma patients in part I. Furthermore, in part II, this thesis focuses on the identification of therapeutic interventions aimed at reducing endothelial permeability and organ failure: 1) via altering the ADAMTS-13-Von Willebrand Factor axis and 2) via administration of a tyrosine kinase inhibitor during the resuscitation of trauma-induced shock. - Persistent Identifier
- https://hdl.handle.net/11245.1/1158a943-4a95-446b-9bf4-8c44cb762d4b
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction
Chapter 2: Platelet-to-red blood cell ratio and mortality in bleeding trauma patients: A systematic review and meta-analysis
Chapter 3: Use of a high platelet-to-RBC ratio of 2:1 is more effective in correcting trauma induced coagulopathy than a ratio of 1:1 in a rat multiple trauma transfusion model
Chapter 4: The use of frozen platelets for the treatment of bleeding
Chapter 5: The use of cryopreserved platelets in a trauma-induced hemorrhage model
Chapter 6: The effects of platelet products on the induction of lung injury in a mechanical ventilation model
Chapter 7: Targeting endothelial dysfunction in acute critical illness to reduce organ failure
Chapter 8: Early increase in anti-inflammatory biomarkers is associated with the development of multiple organ dysfunction syndrome in severely injured trauma patients
Chapter 9: Plasma and rhADAMTS13 reduce trauma-induced organ failure by restoring the ADAMTS13-VWF axis
Chapter 10: Bosutinib reduces endothelial permeability and organ failure in a rat polytrauma transfusion model
Chapter 11: Summary and general discussion: ‘Novel treatments for trauma-induced bleeding and organ failure’
Chapter 12: Nederlandse samenvatting: ‘Nieuwe behandelstrategieën voor trauma-geïnduceerde bloeding en orgaan falen’
Acknowledgements; Dankwoord; Bibliography; Curriculum vitae; PhD portfolio
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