Novel treatments for trauma-induced bleeding and organ failure

Research output: PhD ThesisPhD-Thesis - Research and graduation internal

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.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam, Netherlands
Supervisors/Advisors
  • Juffermans, Nicole P., Supervisor
  • Hollmann, Markus W., Supervisor
Award date30 Sep 2021
Print ISBNs9789464166972
Publication statusPublished - 2021

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