Structure-based design of therapeutics to control hemostasis

ABSTRACT: Hemorrhage causes millions of deaths and hundreds of billions of dollars in medical costs every year, and a large percentage of trauma bleeding-associated deaths occur in the prehospital setting. Bleeding is typically treated with transfused blood products, but this is difficult in the prehospital setting due to limitations in transportation and storage, especially in rural and remote military settings. Advancements in cold-stored platelets and lyophilized blood products have the potential to address some of these limitations. However, devising novel products that continue to improve shelf life, portability, scalability, cost, and safety for patients experiencing bleeding in prehospital settings could greatly improve treatment options and patient outcomes. This review primarily focuses on rational design of material-based approaches to develop novel hemostatic agents that strive to meet limitations of current blood products, especially for use in the prehospital setting. Key topics of consideration include how material design can lead to identification of effective therapies that stop bleeding as well as strategies to iterate on existing designs to enhance healing after cessation of bleeding. Improving performance and functionality of existing and emerging materials could be achieved through the incorporation of transglutaminases, growth factors, cellular components, or inorganic molecules. Finally, consideration of patient-specific factors that influence bleeding, such as patient sex and age, through evaluation of therapies in specific populations and/or design of materials targeted for specific patient populations, is a key area for development of next-generation hemostatic materials.