Identification of Multiple Levels of Trauma Induced Coagulopathy

Trauma continues to be a major cause of death across the globe. While the exact causes of trauma differ greatly between the military and civilian lifestyles, the ability to stop bleeding after trauma is paramount for survival. Over the past decade coagulation research has transitioned from a classical understanding of plasma based protein coagulation to the current cell focused research. As part of this shift, platelets have become a central player in hemostasis. Unfortunately little is currently understood about how platelet function is affected by trauma. In an effort to better define platelet function during trauma and the resulting shock from exsanguination, a multipronged approach was developed. The hypothesis that the introduction of a state of clinical shock in a controlled environment would allow for an in-depth assessment of trauma-induced coagulopathy led to the development of a swine based model of hemorrhagic shock. In this model a composite injury consisting of soft tissue damage, long bone fracture, and controlled hemorrhage was used to induce a moderate state of hypovolemic shock. As a result of this injury the animals showed both the beginning of a plasma protein consumption coagulopathy as well as kinetic quickening in the clotting process. These surprising results show competing up-regulation and down-regulation of the coagulation system in response to trauma induced shock. To better define the effect of polytrauma on platelet function in a human population a clinical study was conducted. The hypothesis behind the development of this study was that the examination of platelet function during polytrauma would lead to a more complete understanding of the effects of trauma on hemostasis. This study resulted in the identification of two separate but not mutually exclusive coagulopathies in response to trauma. The first was the traditional consumption based coagulopathies recently suggested to be varying degrees of disseminated intravascular coagulopathy. The second was a development a hypercoagulable state that may be attributed to increased platelet function. The identification of these two competing coagulopathies in separate models highlights the inadequacies of the current plasma based clinical testing, and the need for increased whole blood testing in the trauma treatment environment.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Year dc:date.available

2013

Author dc:creator

• Newton, Jason

Contributors dc:contributor

• Donald Brophy
• Robert Diegelmann

• Trauma
• Coagulation
• Trauma Induced Coagulopathy
• Platelets
• Shock
• Platelet Function
• Disseminated Intravascular Coagulopathy
• Biochemistry, Biophysics, and Structural Biology
• Life Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/528

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1527