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

Whole blood (WB) transfusion is increasingly used for trauma patients with hemorrhagic shock; however, sex-based differences in utilization and outcomes remain incompletely understood. The purpose of this study was to examine sex-based differences in WB utilization and survival using a large national trauma dataset.

We performed a retrospective cohort study using the 2021 to 2022 American College of Surgeons Trauma Quality Improvement Program database. Trauma patients ( 16 y) with blunt or penetrating trauma, shock index >1, and receipt of 4 units of blood within 4 hours were included. Patients were then stratified by sex and WB receipt within 4 hours. Multivariable logistic regression assessed associations between WB transfusion and 4-hour, 24-hour, and 30-day mortality. Cox proportional hazards models evaluated in-hospital mortality. Models were adjusted for patient demographics, injury characteristics, and institutional factors. Sensitivity analyses using facility-clustered generalized estimating equations (GEE) were performed. Dose-response was evaluated using WB proportion of total transfusion volume within 4 hours.

Among 8,631 patients (6,743 males and 1,888 females), WB was administered more frequently to males (33.8% vs. 22.3%, p <0.001). In adjusted analysis, WB was associated with lower 24-hour mortality among males (odds ratio [OR]: 0.76, 95% confidence interval [CI]: 0.63-0.92, p =0.004) and reduced in-hospital mortality risk (hazard ratio [HR]: 0.88, 95% CI: 0.79-0.99, p =0.028). Facility-clustered models confirmed reduced 24-hour mortality in males (OR 0.77, 95% CI: 0.61-0.96, p =0.022). Increasing WB exposure demonstrated a dose-response association with lower early and in-hospital mortality among males ( p <0.022), with no significant associations observed in females. WB was not associated with increased rates of major complications for either sex.

In this nationwide study, WB was used less frequently in females and was associated with improved survival only among males. These findings underscore the need for prospective studies to clarify biological and systemic contributors to these disparities. ( J Trauma Acute Care Surg. 2026;101: 511-518. Copyright © 2026 Wolters Kluwer Health, LLC. All rights reserved.).

Prognostic/epidemiological; Level III.