The resurgence of whole blood transfusion: Evaluating microcirculatory evidence in hemorrhagic trauma care: A review.

During resuscitation from hemorrhagic shock, fresh whole blood remains the most effective treatment option. However, fresh whole blood is a limited resource, and its availability continues to decline. Thus, blood is preserved as whole blood or as individual components [e.g., plasma, platelets, and red blood cells (RBCs)] for transfusion practices. The quality of red blood cells during storage can be diminished, leading to a set of changes and consequences called storage lesion, resulting in the release of acellular hemoglobin and its degradation products (heme and iron). This acellular Hb causes vasoconstriction and reduces blood flow by oxidative injury and nitric oxide scavenging. Beyond biochemical effects, storage lesion alters blood rheology and RBC biomechanics, further compromising microcirculatory perfusion and oxygen delivery after transfusion.. These morphological changes impair oxygen transport, decrease cell deformability, shorten post‑transfusion circulation time, and disrupt microcirculatory blood flow. In this review, we analyze how different blood storage strategies and component therapies alter cellular biomechanics, hemorheology, and blood endothelial interactions, and how these changes impact the safety and efficacy of transfusions for hemorrhage resuscitation through the lens of microcirculatory perfusion. We also highlight current and emerging markers of storage lesion and microcirculatory function and discuss experimental biochemical approaches to extend shelf life and develop viable transfusion alternatives. While storage techniques for components continue to advance, and blood substitutes face present limitations, we conclude that the low-titer group O whole blood holds immediate promise for significantly improving transfusion medicine and resuscitation outcomes.