Hemostatic erythrocytes for acute non-compressible hemorrhage

Abstract Severe bleeding is a major cause of morbidity and mortality worldwide. The inability to stop non- compressible hemorrhage leads to high mortality in low-resource settings. We aim to engineer hemostatic red blood cells targeted to collagen type I and to fibrin clots (t-RBCs). We hypothesize that t-RBCs will adhere to collagen-I and fibrin in the injured blood vessel and, due to their sizeable corpuscular volume and surface area, will “plug” the bleeding site. Slowing or stopping the bleeding will buy precious time for surgical interventions and resuscitation procedures. Our previously published data support the feasibility of RBC modifications with ligands. RBC is the ideal biomaterial for clot formation due to its availability, biocompatibility, large corpuscular volume, and enormous surface area. This approach has never been explored in emergency medicine. This work will focus on synthesizing t-RBCs, testing the ability to enhance clot formation and stability in vitro, and performing a pilot hemostasis experiment in vivo. We propose the following Specific Aims: 1) engineer t-RBCs and test binding efficiency in vitro; 2) perform hemostasis measurements in vitro using thromboelastography and rheometry; 3) determine the circulation time, binding to the clot, and the effect on hemostasis in an in vivo model. This novel project will impact management and survival in non-compressible hemorrhage.