Whole Blood Reduces Male Trauma Mortality but Shows No Benefit in Females

A nationwide analysis of 8,631 patients finds sex-based disparities in both whole blood utilization and subsequent survival outcomes.

For Doctors in a Hurry

Clinicians lack data on whether sex-based differences influence survival outcomes for trauma patients receiving whole blood transfusions.
The researchers analyzed 8,631 trauma patients from a national database to compare whole blood utilization and mortality by sex.
Whole blood transfusion reduced 24-hour mortality in males with an odds ratio of 0.76 and a 95 percent confidence interval of 0.63-0.92.
The study concludes that whole blood transfusion is associated with improved survival in males but not in female trauma patients.
Future prospective research must investigate biological factors to explain why females receive less whole blood and show different survival outcomes.

The Resurgence of Whole Blood in Hemostatic Resuscitation

Hemorrhage remains the primary preventable cause of death following traumatic injury, necessitating rapid and effective volume replacement to correct coagulopathy and restore perfusion [1]. While conventional resuscitation often relies on a balanced 1:1:1 ratio of component therapy, whole blood has emerged as a preferred alternative because it provides red cells, plasma, and platelets in a single, physiological unit [2]. This approach simplifies the logistics of massive transfusion protocols and has demonstrated the potential to reduce overall component requirements in civilian settings [3, 1]. However, the implementation of whole blood is often complicated by concerns regarding Rhesus factor alloimmunization in females of childbearing potential, leading to variations in utilization across different patient populations [4, 5]. A new nationwide study now examines how these clinical choices and biological factors influence survival outcomes across the sexes.

Analyzing Transfusion Patterns in Massive Hemorrhage

Researchers conducted a retrospective cohort study providing Level IV evidence by analyzing data from the 2021 to 2022 American College of Surgeons Trauma Quality Improvement Program database. This national registry allowed for a comprehensive evaluation of real-world transfusion practices and outcomes across a diverse range of trauma centers. The study focused on a specific population of 8,631 trauma patients who were at least 16 years of age and had sustained either blunt or penetrating injuries. By utilizing this high-volume database, the authors aimed to identify how sex-based differences in the administration of whole blood correlate with clinical survival in the acute setting. To ensure the cohort represented patients in true hemorrhagic shock, the inclusion criteria required a shock index greater than 1. The shock index, which is the ratio of heart rate to systolic blood pressure, serves as a clinical indicator of hemodynamic instability and occult hemorrhage. Furthermore, patients were only included if they received at least 4 units of blood within 4 hours of arrival, a threshold used to identify those requiring massive transfusion protocols for severe hemorrhage. Within this high-acuity group, the researchers identified a significant sex imbalance in the study population, which consisted of 6,743 males and 1,888 females. This distribution reflects broader epidemiological trends in traumatic injury while providing a large enough sample size to analyze sex-specific associations between whole blood utilization and mortality.

Disparities in Utilization and Survival Outcomes

The analysis revealed a significant discrepancy in how clinicians administered whole blood based on patient sex. Despite meeting the same clinical criteria for hemorrhagic shock, whole blood was administered more frequently to males than females (33.8% vs. 22.3%, p<0.001). This utilization gap persisted even though the study population was restricted to high-acuity patients requiring at least 4 units of blood within the first 4 hours of care. To determine if these administration patterns influenced clinical recovery, the researchers evaluated mortality outcomes at three distinct intervals: 4-hour, 24-hour, and 30-day mortality. They also assessed overall in-hospital mortality using Cox proportional hazards models (a statistical method for investigating the association between the survival time of patients and specific predictor variables, such as the type of blood product received). For male patients, the administration of whole blood was associated with a clear survival advantage in the acute and longitudinal phases of care. In the adjusted multivariable logistic regression analysis, whole blood was associated with lower 24-hour mortality among males (OR: 0.76, 95% CI: 0.63-0.92, p=0.004). Furthermore, the use of whole blood in men correlated with a reduced in-hospital mortality risk (HR: 0.88, 95% CI: 0.79-0.99, p=0.028). These findings suggest that for the male cohort, the physiological benefits of whole blood, which provides clotting factors and red cells in a physiological concentration, translated into a measurable reduction in the risk of death during the initial 24 hours and throughout the duration of the hospital stay. In contrast, the survival benefits observed in the male population did not extend to female patients. The researchers found that no significant associations between whole blood and mortality were observed in females across any of the measured time points. While the study was not designed to identify the underlying cause of this divergence, the lack of a survival benefit in women, combined with the lower rates of whole blood utilization (22.3%), suggests a complex interplay of biological factors or potential systemic biases in resuscitation protocols. For the practicing clinician, these data highlight a critical need to investigate why a standard of care that appears effective in one sex does not yield the same outcomes in another, particularly in the high-stakes environment of trauma resuscitation.

Dose-Response Relationships and Safety Profiles

To ensure the robustness of the observed survival benefits in men, the researchers employed a multivariable logistic regression that adjusted for patient demographics, injury characteristics, and institutional factors. They further validated these results using facility-clustered generalized estimating equations (a statistical method that accounts for variations in clinical practice and outcomes between different hospitals by grouping data by facility). This sensitivity analysis confirmed a reduced 24-hour mortality in males (OR 0.77, 95% CI: 0.61-0.96, p=0.022), reinforcing the finding that the survival advantage was not merely a byproduct of treatment at higher-performing trauma centers. These rigorous adjustments suggest that the association between whole blood and improved male survival is independent of the specific facility where the care was delivered. The study also identified a clear dose-response relationship regarding the volume of whole blood administered to male patients. When evaluating the whole blood proportion of total transfusion volume within the first 4 hours of care, the researchers found that increasing whole blood exposure demonstrated a dose-response association with lower early and in-hospital mortality in males (p<0.022). This finding implies that for men in hemorrhagic shock, a higher concentration of whole blood relative to component therapy may provide superior physiological support. Notably, this dose-dependent benefit was absent in the female cohort, where no significant associations between transfusion volume proportions and mortality were observed. Despite the sex-based differences in efficacy, the safety profile of the intervention remained consistent across the entire study population. The researchers reported that whole blood was not associated with increased rates of major complications for either sex, suggesting that the lack of survival benefit in females was not due to an increase in adverse events such as transfusion-related lung injury or thromboembolic complications. For clinicians, these data indicate that while the therapeutic impact of whole blood may currently favor male patients, the administration of the product does not appear to introduce additional clinical risks, supporting its continued use as a safe component of trauma resuscitation protocols.

Study Info

Sex differences in outcomes following whole blood transfusion for patients with severe hemorrhage

Erin Yu, Morihiro Katsura, Caitlyn Braschi, Kazuhide Matsushima, et al.

Journal The Journal of Trauma: Injury, Infection, and Critical Care

Published April 17, 2026