BACKGROUND: Early resuscitation is based on platelet-poor components such as red blood cells and plasma (RBC + P), contributing to platelet dilution and worsening of trauma-induced coagulopathy (TIC). We aimed to compare the ability of cold-stored whole blood (WB) versus RBC + P as a single component to correct TIC. STUDY DESIGN AND METHODS: Blood samples were collected on admission from trauma patients who required activation of the major hemorrhage protocol at a single UK major trauma center in 2021/2022. Samples were spiked ex vivo with volumes equivalent to two, four, or eight units of WB or RBC + P stored for a maximum of 2 weeks. Thromboelastometry, platelet counting, and multiple electrode aggregometry (MEA) were performed. RESULTS: Samples from 20 adult trauma patients were analyzed. Median age was 32 years (27-42), 89% were male, 70% had platelet dysfunction (tissue factor-activated ROTEM [EXTEM]-tissue factor-activated ROTEM with cytochalasin D [FIBTEM] clot amplitude at 5 min [A5] ≤ 30 mm), 65% were coagulopathic (EXTEM A5 ≤ 40 mm), and 42% died. EXTEM-FIBTEM A5 was higher following spiking with WB than RBC + P (33 mm, 26-33, vs. 27 mm, 24-30, p <
.001). WB-spiking corrected platelet dysfunction in 2 patient samples out of 20, whereas RBC + P increased the frequency of platelet dysfunction (1/20 sample) and TIC (4/20 samples). RBC + P was associated with a dose-dependent deterioration in rotational thromboelastometry (ROTEM) clot strength and dynamics, platelet count, and aggregation in response to multiple agonists compared with WB-spiking, which maintained or partially corrected these abnormalities. CONCLUSION: Compared with RBC + P, WB better preserves ex vivo platelet-related ROTEM parameters, platelet count, and aggregation, but does not fully correct these common derangements of TIC.