Original Investigation
Whole-Blood vs Component Therapy in Adult Trauma: An Updated Systematic Review and Meta-Analysis
Wesam Ibrahim, Kenneth Meza Monge, Johannes Menzel, et al
JAMA Surg Published Online: March 11, 2026
doi: 10.1001/jamasurg.2026.0197
Key Points
Question Is whole-blood transfusion associated with reduced mortality compared with component therapy in adult trauma patients?
Findings In this meta-analysis of 40 studies (49 776 patients), whole-blood transfusion, compared with component therapy, was associated with reduced 24-hour mortality in civilians (with moderate-certainty evidence and a wide 95% prediction interval) but not in military settings.
Meaning Moderate-certainty evidence suggests that whole-blood transfusion is associated with early mortality in civilian trauma, although the wide prediction interval indicates substantial heterogeneity requiring patient selection refinement.
Abstract
Importance Hemorrhage remains the leading preventable cause of trauma-related death. The effectiveness of whole-blood vs component therapy remains uncertain, particularly given heterogeneous patient populations and resuscitation protocols.
Objective To determine whether whole-blood transfusion is associated with reduced mortality compared with component therapy in adult trauma patients, with prespecified analysis by civilian vs military settings.
Evidence Review In this updated systematic review and meta-analysis, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and CINAHL were searched from January 1, 2006, through June 30, 2025. Two reviewers independently screened 6888 records and extracted data. Randomized clinical trials and observational studies comparing whole-blood vs component therapy in adults (aged ≥16 years) with traumatic hemorrhage were included. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool was used to assess the risk of bias in observational studies, while the Cochrane Risk of Bias 2 (RoB 2) tool was applied for randomized clinical trials. Random-effects meta-analysis used restricted maximum likelihood with Hartung-Knapp adjustment.
Findings Forty studies (2 randomized clinical trials, 38 cohort studies; n = 49 776) were included. Whole-blood transfusion, compared with component therapy, was associated with reduced 24-hour mortality (odds ratio [OR], 0.76; 95% CI, 0.60-0.95; τ2 = 0.27; I2 = 87%; 95% prediction interval [PI], 0.30-1.89). In civilians (24 studies; n = 39 028), mortality reduction was significant (OR, 0.73; 95% CI, 0.57-0.93; τ2 = 0.27; I2 = 89%; 95% PI, 0.28-1.91), corresponding to an absolute risk reduction of 4.6 percentage points (95% CI, 1.4-8.6 percentage points) based on median control mortality of 20% (range, 15%-25%). No benefit was observed in military settings (5 studies; n = 2171; OR, 0.99; 95% CI, 0.58-1.70). Civilians also showed reduced 30-day mortality (OR, 0.76; 95% CI, 0.60-0.98) and transfusion requirements (mean difference, −2.66 units; 95% CI, −3.96 to −1.35 units).
Conclusions and Relevance In this updated systematic review and meta-analysis, whole-blood transfusion was associated with reduced mortality in civilian but not military adult trauma patients, although the wide 95% PIs suggest substantial heterogeneity, indicating that benefits may vary considerably across settings. These findings support selective whole-blood transfusion protocol implementation in civilian centers while highlighting the need for refined patient selection criteria.
