Reducing the Dependence on Blood with Hemoglobin Based Oxygen Carriers

Red blood cell (RBC) transfusions have been a life-saving procedure following trauma for decades. Ex vivo storage of RBCs is limited to 42 days, as the RBCs degrade during storage. Recent evidence suggests that transfusions of stored RBCs are associated with adverse events and increased mortality. Blood shortages are frequent and are expected to increase as the population ages. My research explored new methods to prolong ex vivo RBC storage, and alternatives to RBCs. A novel improvement to RBC storage is storage under anaerobic conditions to minimize oxidative stress. Anaerobically stored RBCs improved RBC recovery and resuscitation from hemorrhagic shock compared to conventionally stored RBCs. However, anaerobic storage only slowed the degradation of RBCs, without further extending the RBC storage period. Therefore, we explored hemoglobin (Hb)-based O2 carriers (HBOCs) as an alternative to RBCs. HBOCs are advantageous relative to blood, as they are shelf-stable, not limited by donors for supply, and do not require blood-type matching before infusion. Clinical trials of previous generations of HBOCs failed due to unforeseen side-effects. The next generation of HBOCs involves high molecular weight Polymerized Hb (PolyHb), which is the most promising and scalable HBOC formulation that alleviates the side effects of previous HBOCs. We compared fresh and stored PolyHb to RBCs in a hemorrhagic shock resuscitation model. The results confirm that PolyHb was as effective as fresh RBCs to recover from shock and significantly superior to stored RBCs, and that PolyHb’s properties or efficacy did not change during long term storage. Finally, we assessed the safety of PolyHb in guinea pigs, as they are more human-relevant than other preclinical models. This study demonstrated that increasing the molecular size of PolyHb alleviates side-effects of previous HBOC formulations, and that PolyHb toxicity is transient. Future work will focus on the safety of PolyHb, particularly in vulnerable patient populations