Novel Artificial Erythrocyte for In-Field Resuscitation of Hemorrhagic Shock
Abstract
Bleeding accounts for ~90% of potentially survivable battlefield deaths: lives that could be saved with improved, field-ready blood, blood components, or blood substitutes. Researchers and clinicians have learned that for those in shock from traumatic bleeding, effective resuscitation requires replacement of lost blood volume with fluid capable of transporting oxygen from lungs to tissue (rather than just with physiologic salt solutions). Moreover, with massive blood loss or with ongoing bleeding from non-compressible injuries, resuscitation with an oxygen carrier alone may be complicated by problems with the clotting system (either by diluting key elements in blood plasma or because of disruption in clotting that arises from severe tissue injury), particularly in prolonged field care (PFC) scenarios. A field-deployable oxygen carrier that is compatible with freeze-dried clotting factors and platelets from human plasma will enable balanced on-scene resuscitation that treats both shock and bleeding problems during the critical "golden-hours" after injury. Such resuscitation may be used in the field as a bridge to natural blood replacement, prior to and during transport to central facilities. To address this need, we developed ErythroMer (EM), a first-in-class, biosynthetic, nano-cyte blood substitute that mimics human red blood cell physiology in all key respects and surmounts the barriers to success that have frustrated development of other blood substitutes. Key EM innovations include: (1) shape similar to red blood cells; (2) freeze-dried formulation with sustained shelf stability under ambient conditions that is also easy to use in the field (just add water); (3) physiologic oxygen binding/release; (4) composition that prevents hemoglobin oxidation ("rusting") during circulation; and (5) limited interference with control of blood vessel caliber (otherwise, could cause heart attack or stroke). As such, EM development, alone or in combination with similarly freeze-dried/easily reconstituted clotting factors, may transform PFC outcomes and help realize our goal of zero preventable deaths after injury. Our overall objective for this project is to refine a novel blood substitute (EM), in combination with field-deployable clotting factors from human plasma, for in-field resuscitation of combat victims with severe hemorrhagic shock. Our hypotheses are that the modular EM design enables creation of prototypes with optimized oxygen binding and the development of dosing strategies suitable for PFC in austere settings and, that during such care for hemorrhagic shock and polytrauma, EM administration with clotting factors will improve mortality via improved oxygen delivery and cessation of bleeding. We will accomplish our objective by completing the following tasks: Task 1: Craft EM prototypes with specialized oxygen binding features that will be effective even if there are major problems with either the respiratory system (capturing oxygen in the lung) or the circulatory system (delivering oxygen to tissues). Task 2: Optimize EM structure and dosing strategy to maintain circulation for the prolonged periods required for challenging in-field care (up to 2 days). Task 3: Determine EM compatibility with freeze-dried components of the human clotting system and develop a goal-directed algorithm fixing the clotting problems that develop in casualties with shock from massive bleeding. Task 4: Establish EM effectiveness and safety with/without freeze-dried clotting factors in animal models of hemorrhagic shock (and multiple, complicated injuries) that simulate PFC. Our multidisciplinary, experienced team (with strong academic and biotech industry partnerships) will employ a robust suite of state-of-the-art bench-testing platforms and novel living-animal models to complete the tasks and rigorously test the hypotheses outlined above. Our plans calls for interactive experimental testing and virtual modeling to refine the EM
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710668
Entities
People
- Allan Doctor
Organizations
- United States Army
- Washington University in St. Louis