A Healthier Wisconsin

Determining the Contribution of Fibrinolysis to Blood Loss in Severe Hemorrhage Using RNA Therapy

Developing new strategies to reduce blood loss in trauma patients

Full Project Name:Determining the Contribution of Fibrinolysis to Blood Loss in Severe Hemorrhage Using RNA TherapyPrincipal Investigator:Christian Kastrup, PhD, SurgeryCo-Investigator:Marc de Moya, MD, SurgeryAward Amount:$200,000
Award Date
Project Duration:24 months

Project Description Narrative:

Decreasing mortality and morbidity from trauma and severe hemorrhage is a priority to protect the health of the people of Wisconsin and improve health equity.

Gunshot wounds are an essential trauma class strongly associated with health disparities. There are currently more than 200 firearms-related deaths in Wisconsin each year and an additional 700-plus non-fatal shootings. Most of these gun-related injuries are geospatially localized in Milwaukee. The resulting mortality, morbidity, and psychological trauma contribute to health inequities. Hemorrhage is the second-leading cause of death worldwide and the leading cause of preventable death in trauma. Analyses of trauma mortality indicate that 25% of pre-hospital deaths are preventable, of which 90% are attributable to hemorrhage.

The proposed project addresses an important fundamental question in the biology of hemostasis (blood clotting) and hemorrhage control: to what extent does fibrinolysis (the natural enzymatic degradation of blood clots) act in parallel to blood coagulation (clot formation) during severe hemorrhage. New knowledge generated from the proposed project could decrease the cost burden on healthcare systems by minimizing the quantity of blood products, and decrease operating room time, patient recovery time, and the frequency and severity of complications.

Project Updates:

  • Discovered that rotational thromboelastography on blood samples demonstrated inhibition of fibrinolysis in swine treated with siPlasminogen
  • Refined a swine model of junctional hemorrhage and proceeding with testing the effect of plasminogen knockdown on junctional hemorrhage in swine
  • Demonstrated the ability to knockdown a circulating blood protein in swine using siRNA-LNP technology

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