SanguiStop: Intravenous Nanomedicine for Targeted Thrombin Delivery in Hemorrhage Control
Abstract
Traumatic hemorrhage remains a primary cause of 'preventable mortality' in austere battlefield conditions for our military. Consequently, the Joint Program Committee-6/Combat Casualty Care. Research Program (JPC-6/CCCRP) emphasizes 'hemorrhage control and resuscitation' as one of the primary focus areas of research towards developing knowledge and materiel solutions for 'on field' mitigation of combat trauma. Robust clinical studies (e.g., PROMMTT, PROPPR, COMBAT and PAMPer), have established that mortality from severe traumatic hemorrhage usually happens within minutes-to-hours post-injury and early intervention via transfusion of whole blood (WB) or its components can significantly improve survival in these patients. While such transfusion strategies are significantly effective in saving lives, implementing them beyond large civilian and military trauma treatment facilities has significant logistical and functional limitations. Among all blood components, platelets play the most critical role in hemorrhage control and yet they present the highest logistical challenges in 'field deployability' and far forward use. Platelets actively stanch bleeding from the injury site by (i) rapidly adhering and aggregating at the bleeding site to form a hemostatic plug (primary hemostasis) and (ii) serving as a procoagulant amplifier by presenting anionic phospholipids, e.g. phosphatidylserine (PS), on the activated platelet surface to render coagulation factor co-localization for tenase and prothrombinase assemblies leading to thrombin burst. The thrombin converts fibrinogen (Fg) to fibrin which then self-assembles and undergoes FXIIIa-mediated crosslinking to secure the hemostatic clot. Consequently, trauma- associated platelet depletion and platelet dysfunction, severely compromise hemostatic function resulting in uncontrolled bleeding.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1215026
Entities
People
- Anirban S. Gupta
- Bipin Paruchuri
- Hanyang Wang
- Rohini Sekar
Organizations
- Case Western Reserve University