Blood Storage Related Mortality and Adverse Effects in Trauma Patients

Is Long-Term Blood Storage related with increased mortality and adverse effects in severely injured trauma patients?

Abstract

Background: Severe trauma remains a significant cause of mortality, often necessitating massive transfusion. During storage, red blood cells (RBCs) and whole blood units develop "storage lesions," encompassing biochemical and structural deteriorations such as oxidative damage to hemoglobin, metabolic derangements (e.g., lactate accumulation, adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) depletion), and increased vesiculation. These changes are hypothesized to contribute to adverse clinical outcomes, including impaired microvascular perfusion, endothelial injury, hypercoagulability, inflammation, multi-organ dysfunction, and increased mortality. While numerous observational studies and meta-analyses suggest an association between prolonged blood storage duration and worse outcomes, large randomized controlled trials (RCTs) have yielded conflicting results. The impact of storage age on high-risk trauma patients requiring massive transfusion remains particularly uncertain.

Objective: This study aims to evaluate the effect of RBC and whole blood storage duration on 28-day mortality in severely injured trauma patients (Injury Severity Score (ISS) >15) undergoing massive transfusion. A secondary objective is to assess the relationship between storage duration and morbidity, including complications such as cardiac ischemia, thromboembolic events, acute respiratory failure, nosocomial infection, and multiple organ failure.

Methods: A single-center retrospective cohort study will be conducted at the University of Florida Jacksonville Shands Hospital. The study will include patients aged 18-75, with an ISS >15, who presented directly from the injury scene and received massive transfusion (defined as >10 packed RBC (PRBC) units in the first 24 hours or ≥3 units in 1 hour) between January 1, 2023, and October 1, 2025. Data will be extracted from hospital information systems and anesthesia records. The storage duration for each transfused unit (from collection to transfusion) will be recorded. Blood products are preserved with Adsol AS-1 additive solution, allowing storage of packed RBCs for 42 days and whole blood for 21 days.

Patients will be analyzed based on the product type (PRBCs vs. whole blood) and stratified into storage duration groups: Group 1 (0-7 days), Group 2 (8-14 days), Group 3 (15-21 days), and Group 4 (≥22 days, for PRBCs only). Comprehensive data will be collected, including demographics, injury mechanism, physiological parameters (vital signs, blood gas analyses including lactate, HCO₃, Hb, pH), laboratory values (e.g., creatinine), transfusion volumes (RBC, fresh frozen plasma (FFP), platelets, cryoprecipitate), fluid administration, urine output, vasopressor requirements, and perioperative complications. Outcomes of interest are 28-day mortality, morbidity endpoints, and lengths of intensive care unit (ICU) and hospital stay.

Statistical Analysis: Statistical analyses will be performed using R software. Descriptive statistics will summarize the data. Normality will be assessed using the Shapiro-Wilk test. Group comparisons will utilize t-tests, Mann-Whitney U tests, ANOVA, or Wilcoxon tests as appropriate. Categorical data will be compared using Pearson's chi-square or Fisher's exact tests. Correlations will be assessed via Spearman's analysis. Linear and logistic regression models will identify factors influencing continuous outcomes (e.g., ICU stay) and binary outcomes (e.g., mortality, complications), respectively. Survival analysis will employ Kaplan-Meier curves and the Log-Rank test. A p-value <0.05 will be considered statistically significant.

Conclusion: This retrospective cohort study seeks to clarify the contentious relationship between the age of transfused blood and clinical outcomes in a high-risk population of major trauma patients requiring massive transfusion. By specifically focusing on this vulnerable group and employing detailed stratification of storage duration, the study aims to provide evidence on whether the transfusion of older blood units is associated with increased 28-day mortality and higher morbidity. The findings could inform blood bank inventory management and transfusion practices in trauma resuscitation.

Inclusion criteria

• Patients between 18-75 years of age,
• Injury Severity Score>15 and have received massive blood transfusions in our hospital from 1 January 2015 to 31 December 2025
• The patients admitted because of trauma and undergoing surgery

Exclusion criteria

• Patients with known cardiac or vascular diseases such as heart failure or malignant hypertension, those under anticoagulant treatment
• Patients with known serious kidney (on dialysis), lung, liver diseases, those under anticoagulant treatment
• Super obese patients with body mass index (BMI) 50 or above