Materials and Mechanisms for Understanding and Controlling Hemorrhage

Hemorrhage is a leading killer in Canada and throughout the world, particularly of young healthy adults. It is a multifaceted problem that occurs in diverse clinical scenarios, such as trauma, childbirth, and surgery. Many therapeutic strategies exist, but they are not effective in the most severe, intractable cases of hemorrhage. The presentation will discuss three directions we are taking to halt previously intractable hemorrhages following trauma, using biochemical engineering. Improving the biophysical transport of external hemostatic agents within wounds. We found that externally-applied hemostatic molecules do not adequately reach damaged blood vessels due to outward blood flow. We have developed a new strategy of transporting therapeutics into wounds for managing trauma-induced hemorrhage. This has been have verified in large-animal models, and we are working to develop this for use in the clinic. Increasing the coagulability of platelets transfused for hemorrhage. During trauma, platelet activation and aggregation often becomes defective. We have developed unique technologies for loading platelets with therapeutic cargo, and are working to test if these modified platelets are more efficacious in treating hemorrhage than traditional platelet transfusions. Enhancing the adhesion of clots. Clots are biological glues that must strongly adhere to seal wounds. We have identified pathologic mechanisms that degrade the enzyme responsible for adhesion (coagulation factor XIIIa), and are working to develop new way to increase clot adhesion and seal large wounds. Through these three themes, we are identifying new biochemical and biophysical mechanisms and innovative strategies for treating hemorrhage. The long-term impact is expected to be specific therapies to reduce mortality from trauma-related hemorrhage; the insights may extend to treating postpartum or surgical hemorrhage.