Systemic and microcirculatory safety profile and efficacy of stored low-titer group O whole blood and a novel scavenger protein cocktail

Background and Objective: Hemorrhagic shock is a leading cause of morbidity and mortality in trauma and surgical settings. Although component therapy is standard of care, whole-blood transfusion is recommended to provide hemostatic and oxygen-carrying benefits. During storage, red blood cells undergo hemolysis, releasing hemoglobin and activating inflammatory pathways, which cause vasoconstriction, oxidative stress, and injury after transfusion. This study compares the macro- and microcirculatory recovery from resuscitation from hemorrhagic shock using fresh and stored whole blood. This study also evaluates an experimental scavenger protein cocktail (SPC) developed to bind free hemoglobin, heme, and iron to mitigate toxicity and increase the safety profile of stored whole blood units. Methods: A randomized, controlled study was performed using adult Golden Syrian hamsters outfitted with a dorsal skinfold window chamber and carotid artery catheter, subjected to hemorrhage (50% blood volume), kept in hypovolemic shock for 30 minutes, and resuscitated via transfusion of 50% of the shed volume. The hemolysis index (HI) of stored blood transfusions was defined as the product of plasma Hb concentration (g/dL) and the plasma volume fraction (%). Transfusion groups consisted of stored (0–35-day-old) WB with low hemolysis (HI < 0.5), moderate hemolysis (0.5 < HI < 1.5), with severe hemolysis (1.5 < HI < 4.0), and each stored WB group pretreated with the SPC. Systemic and microcirculatory measurements were taken at baseline, shock, 30 minutes after resuscitation, and 60 minutes after resuscitation. Results: Transfusion HI had a strong, highly significant negative correlation with animal hematocrit, microvascular flow, and functional capillary density (FCD) at both 30 and 60 minutes after transfusion. Transfusion HI had a strong, highly significant positive correlation with animal blood pH and lactate accumulation 60 minutes after transfusion. The high HI WB + SPC group demonstrated improved FCD and microvascular flow 60 minutes after resuscitation compared to those without the SPC. The moderate HI WB + SPC group had increased vasodilation and microvascular flow at 30 and 60 minutes in all vessels compared to those without the SPC. There was no significant hematocrit, pH, or lactate level recovery to baseline between the WB and WB + SPC groups. Conclusions: Fresh WB demonstrated superior hemodynamic and microcirculatory recovery compared to stored WB, with outcomes strongly correlated to HI. Stored WB with low HI exhibited comparable efficacy to fresh WB, while moderate and stored WB with high HI were associated with impaired microvascular perfusion, metabolic imbalance, and greater tissue injury. Pretreatment with the SPC partially mitigated microcirculatory dysfunction in higher HI groups, although its hemodilution effect limited full systemic recovery. These findings suggest that minimizing HI in stored WB and optimizing SPC dosing enhances transfusion safety and efficacy This work was supported by DoD Grant Award HT9425-24-1-0238 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.