| Abstract Scope |
Disseminated intravascular coagulation (DIC) is a pathological process causing systemic coagulopathy through excessive thrombin generation. While over-activation of clotting causes microthrombi throughout the body and multi-organ failure, DIC can also contribute to bleeding as clotting factors are consumed. Treatment for either presentation is opposing, creating therapeutic dilemmas in management. Different clinical events can lead to DIC, including cancer, trauma, and infection, including SARS-CoV-2 infection. DIC is associated with increased mortality and has arisen as a potential contributor to morality in COVID-19. This study developed fibrin-specific core-shell nanogels (FSNs) loaded with tissue plasminogen activator (tPA) for targeted clot dissolution to manage microthrombi and the potential consumptive coagulopathy in DIC. tPA-FSNs decreased multiorgan microthrombi presentation, recovered platelet counts, and improved bleeding outcomes in a DIC rodent model. When incorporated with human DIC patient plasma, tPA-FSNs restored clot properties. Together, these data demonstrate that tPA-FSNs could improve DIC outcomes. |