Whole-Blood Transfusion From Empiricism to Evidence

Importance: Hemorrhage remains the leading preventable cause of trauma death, and many fatalities occur before definitive hemorrhage control. Whole blood has reemerged as a promising strategy for early hemostatic resuscitation. However, its modern role remains incompletely defined because the available evidence is heterogeneous and the adoption of whole blood is shaped by safety considerations, implementation challenges, and inequities in access. Observation: Whole blood delivers red cells, plasma factors, and platelets in physiologic proportions through a single product, compressing the time to hemostatic resuscitation and reducing the assembly burden inherent to component therapy. Military experience, observational civilian studies, and emerging prehospital data suggest potential benefits in selected patients, including reduced transfusion burden and improved early outcomes, but the literature remains heterogeneous and is composed predominantly of observational studies. Safety considerations, implementation complexity, and inequities in access continue to shape how whole blood is used in practice. Conclusions and Relevance: The accumulated military, civilian, and prehospital literature supports whole blood as an efficient, physiologically complete strategy for early hemorrhage resuscitation that is associated with reduced transfusion burden and may improve outcomes in selected patients. However, much of the available evidence is observational, and definitive guidance awaits adequately powered randomized trials. For surgeons, trauma teams, and health systems, whole blood offers a practical framework to accelerate hemostatic resuscitation, reduce operational complexity, and inform future implementation in high-risk populations.