Grant: CIHR Fellowship

Thrombotic diseases, including arterial thrombosis (e.g., heart disease) and venous thromboembolism (e.g., deep vein thrombosis (DVT) and pulmonary embolism (PE)), are a significant public health concern that carries high rates of morbidity and represent the leading cause of death worldwide. Those pathologies are the consequence of the formation of a blood clot (thrombus), inside either an artery or a vein, that block the blood circulation to a tissue or region of the body such as the brain (stroke), lower leg (DVT), or lungs (PE). Preventive therapies are available today, which are known as anticoagulants and antiplatelets (e.g., heparin, warfarin and ASA). However, these treatments confer a significant risk of bleeding for the patient. Thus, better defining fundamental mechanisms of thrombosis is critical to developing more effective antithrombotic therapeutic strategies that do not also impose bleeding. In this proposal, key interactions between the two primary components of the blood clot, fibrin(ogen) and platelets, will be investigated. Innovative genetically modified animal models carrying genetic modifications that eliminate important platelet binding sites on fibrin(ogen) will be analyzed in the context of well characterized experimental settings of arterial and venous thrombosis. The studies conducted here will identify new treatment strategies to help prevent and treat thrombotic diseases to reduce a significant health burden among Canadians.