Grant: Doctoral Research Award: Canada Graduate Scholarships

Extracorporeal membrane oxygenation (ECMO) is a form of mechanical circulation of blood, used to bypass the hearts and/or lungs of very sick patients. Blood is pumped through a series of medical devices that act as an artificial lung. When blood comes into contact with these devices, however, it can become activated and trigger blood coagulation, leading to pathogenic clots that can cause these machines to fail, and put patients at risk of deadly pulmonary embolism or ischemic stroke. Anticoagulation is the treatment currently used to stop these clots from forming; unfortunately, bleeding is also a common complication of ECMO, and the risk of bleeding events, such as intracerebral or pulmonary hemorrhage is exacerbated by anticoagulants. A new therapeutic option must be developed to stop these clots from forming, without adding to the risk of bleeding. Coagulation factor XIII (FXIII) has long been considered a promising target to prevent thrombosis while avoiding bleeding risks. I recently published findings that a novel agent, the first to be effective for long-term inhibition of FXIII in vivo, reduced the burden of pathological clots while maintaining hemostasis, in vivo (Strilchuk, et al. Blood, 2020). The current project seeks to build upon these findings, testing the hypothesis that this novel agent will limit unwanted clotting during ECMO, while not increasing the risk of bleeding or pulmonary embolism. Well established in vivo models of ECMO and thromboembolism will be used to assess the efficacy of this novel agent at preventing clots from forming, while bleeding events are monitored. These experiments will be supported with ex vivo characterization of clot structure, an indicator of clot severity. If successful, this project will point to a new mechanism that can be used to prevent the deadly complications associated with ECMO, and provide valuable information on the efficacy and safety of this novel agent as a potential therapeutic.