Dose-Dependent Effects of Whole Blood Transfusion on Associated Infection Risk in Trauma

Authors:
Hadi Hamdan, Ahmad El Nouiri, Camden Gardner, Drishti Lall, Kurt Kralovich, Jeffrey Johnson

Body of Abstract:
Background: Whole blood (WB) transfusion has emerged in trauma resuscitation as a method associated with improved survival over component therapy (CT), largely attributed to reduced hemorrhagic deaths. However, WB is a biologically complex fluid with distinct immunologic and volume-expanding properties that may affect infection risk differently than CT. Although infections have often been secondary outcomes in transfusion studies, their direct relationship with WB use remains unclear. We hypothesized that a higher WB-to-total-transfusion ratio would be associated with lower rates of nosocomial infection in a dose-dependent manner.

Methods: Adult trauma patients from the 2020–2023 national TQIP database who received transfusion were included. The WB ratio was defined as the proportion of total transfused volume given as WB. Outcomes were examined across the full ratio range (0–1), with extremes (CT-only vs WB-only) analyzed separately to confirm consistency. Variables significant on univariate analysis were entered into multivariable logistic regression models evaluating associations between WB ratio and infection outcomes: severe sepsis, surgical site infections, catheter-associated urinary tract infection (CAUTI), and central-line associated bloodstream infection (CLABSI). Models adjusted for demographics, physiology, injury severity, comorbidities, transfusion volume, and hospital characteristics. A subanalysis of ventilated ICU patients assessed ventilator-associated pneumonia (VAP), additionally adjusting for ICU stay and ventilator days.

Results: Among 221,142 transfused patients, 79.8% received CT only, 8.7% WB only, and 11.5% both. Increasing WB ratio was associated with lower odds of severe sepsis (aOR 0.82, p = 0.006), superficial SSI (aOR 0.79, p = 0.020), and CAUTI (aOR 0.73, p = 0.012). At the extremes, WB-only versus CT-only showed similar reductions in severe sepsis (aOR 0.74, p = 0.001), superficial SSI (aOR 0.73, p = 0.008), deep SSI (aOR 0.79, p = 0.028), organ/space SSI (aOR 0.65, p < 0.001), and CAUTI (aOR 0.73, p = 0.021), with no difference in CLABSI. In the ventilated ICU subanalysis (n = 94,206), higher WB ratio was associated with increased odds of VAP (aOR 1.21, p < 0.001), and this persisted when comparing WB-only to CT-only. Across models, older age, higher ISS, diabetes, steroid use, chemotherapy, and longer hospitalization remained independent infection predictors. Conclusion: Our findings demonstrate a consistent, dose-dependent protective association between increasing WB ratio and several nosocomial infections in trauma patients, an effect that remained stable at the extremes of transfusion practice (WB-only vs CT-only). However, this trend did not extend to ventilator-associated pneumonia, which increased with higher WB exposure. These results highlight a potentially heterogeneous effect of WB transfusion across infection types and support further study into the mechanisms and optimal transfusion balance.