Bryan A. Cotton

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Background: The Early Cold Stored Platelet Transfusion Following Severe Trauma Injury Trial evaluated the safety and efficacy of cold stored platelet (CSP) transfusion in injured patients at risk of hemorrhagic shock. It was a phase II, multicenter, randomized clinical trial conducted from June 2022 to September 2023 at five US level 1 trauma centers. A total of 200 adult patients at risk of hemorrhagic shock (102 CSP, 98 standard care (SC)) were included. Median age was 34±13 years, 85% were males, and injury severity was similar between groups. The original frequentist analysis did not demonstrate a statistically significant difference in 24-hour mortality between CSP (5.9%) transfusion and SC (10.2%, p=0.28). Methods: To provide further insight into these findings, a Bayesian logistic regression outcome model with an uninformative prior was performed. To validate the findings further, a sensitivity analysis was performed in addition to analysis using a beta-binomial Bayesian model. Results: The Bayesian logistic regression model yielded an 89.1% posterior probability that CSP transfusion reduced 24-hour mortality (ß ₁ =−0.668, 95% highest posterior density interval: −1.7 to 0.48). This posterior distribution indicates it is 8.1 times more likely that CSP transfusion improves 24-hour mortality than not. Sensitivity analyses across a spectrum of priors consistently produced posterior probabilities >81%. The beta-binomial model demonstrated a similar 86.2% probability that CSP transfusion reduced 24-hour mortality. Conclusion: These findings suggest a high likelihood of mortality benefit with early CSP transfusion in injured patients at risk of hemorrhagic shock and illustrate the added interpretive value of Bayesian analysis in trauma trials with low event rates. Level of evidence: Level II—therapeutic/care management.

BACKGROUND: Blood transfusion and hemorrhage control procedures can be unreliable surrogates for bleeding requiring intervention in children. Some receive unnecessary blood transfusions or lack intraoperative findings for hemorrhage, while others die before an intervention occurs. Standardized criteria for adjudicating the presence of actionable hemorrhage are needed. We aimed to define expert consensus criteria for retrospectively identifying actionable hemorrhage within 6 hours of emergency department (ED) arrival. METHODS: Experts from six specialties involved in pediatric trauma care participated in a modified Delphi study. Panelists were prompted to consider “actionable hemorrhage” as “severe bleeding or injuries at risk of progression to class III or IV shock without prompt intervention.” In Round 1, panelists answered five free-response questions identifying criteria for actionable hemorrhage, including indicators for transfusion and hemorrhage control procedures, postmortem findings, and other relevant factors. Responses were consolidated and rated on a five-point strength-of-indication scale in subsequent rounds. Consensus was defined a priori as ≥70% agreement among panelists. Stability of consensus ( p >0.05) between rounds was assessed using the Wilcoxon Signed-Rank Test. RESULTS: Three Delphi rounds were required to achieve a stable consensus. Twenty-nine of 32 participating panelists participated in all three rounds. Thirteen statements achieved stable consensus as strong indicators of actionable hemorrhage. Criteria with the highest agreement included partial/total resection of intrathoracic/abdominal bleeding solid organs (96.4%), hemoglobinJ Trauma Acute Care Surg . 2026;00:00-00. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.) LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level III.

Background: In cases of massive transfusion, intravenous access can be limited. Additionally, delivering different products through separate lines and infusion methods adds unnecessary steps. RBC, plasma, and whole blood (WB) are delivered via rapid infusers; cryoprecipitate (CRYO) is infused through separate access and is not approved with these devices. Study Design and Methods: We examined the impact of different transfusion methods on hemostatic performance and factor activity using two available CRYO products. Ten bags of CRYO, ten bags pathogen‐reduced CRYO (Intercept® Fibrinogen Complex, IFC), and 20 units of WB were obtained. Each CRYO bag was infused with one unit of WB by three techniques: (1) gravity infusion with filter, (2) rapid infuser at 70 mL/min, and (3) pressure bag and filter. Hemostatic potential was measured by thrombelastography (TEG), thrombin generation (CAT), and factor levels (ACLTOP). Post‐each infusion, disposable tubing and infusion parts were inspected for evidence of clumping or clogging. Results: Both standard CRYO and IFC demonstrated maintained or improved TEG, CAT, and factor levels when subjected to a rapid infuser device and pressure bag. When compared with gravity infusion, a rapid infuser device and pressure bag demonstrated maintained or improved values by TEG, CAT, and factor activity. No evidence of clumping or clogging of tubing was encountered in the 20 runs performed. No evidence of system dysfunction with use of CRYO through these devices was found either. Discussion: Restriction of CRYO infusion through rapid infuser devices or with pressure bags should be reconsidered. Future clinical trials are warranted.

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma‐induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex. Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female‐derived blood products to mitigate endotheliopathy and coagulopathy. Results: Literature suggests that the female sex, particularly the pre‐menopausal age group, possesses an intrinsic advantage linked to circulating estradiol. Estrogen supplementation is noted to mitigate bleeding risks, as clinical reviews in surgical and critical care settings consistently demonstrated a reduction in transfusion requirements and improved hemostasis after administering conjugated estrogen. Current literature findings underscore the therapeutic utility of estrogen in targeting endotheliopathy and coagulopathy. Conclusion: The evidence suggests that estrogen plays a critical, context‐dependent role. One of the most compelling benefits is estrogen's capacity to maintain endothelial integrity, thereby correcting trauma‐induced endotheliopathy. This mechanism, coupled with its inherent procoagulant effect, underlies the observed female survival advantage. Targeting this sex‐based mechanism is a promising avenue to enhance trauma management. Future large‐scale, randomized controlled trials are needed to validate the efficacy of direct estrogen supplementation and the strategic utilization of female‐donated blood products in trauma resuscitation.

In this edition of the THOR supplement in Transfusion , there are two articles that deal with resuscitation futility and transfusion. In one article, Yazer et al. delve into the details of the studies outlined in this editorial and summarize the literature on the topic of transfusion and futility. The second article by Dr. Jay Malone discusses the ethical issues surrounding massive transfusion and resuscitation. Taken together, these articles address the clinical and ethical issues surrounding this very emotive and difficult topic.

Introduction: Recent studies have linked trauma patient outcomes to the plasma donor's sex, with premenopausal females associated with improved survival and lower organ failure. Currently, green‐colored plasma (due to oral contraceptive use) is removed from the donor pool. We set out to evaluate the hemostatic potential of green plasma. Study Design & Methods: We obtained 90 units of plasma from our regional blood center: 30 units of visible green plasma and 60 units of standard‐color plasma divided between male and female donors. We collected clinical data such as age, sex, ethnicity, and number of pregnancies. We then assessed the hemostatic potential through thrombelastography ( TEG ), calibrated automated thrombography ( CAT ), and clotting factor levels. Results: Green plasma unit donors were younger than standard‐color female and male donor units (median age 27 vs. 58 vs. 54) and had fewer pregnancies than their non‐green female counterparts (median 0 vs. 2); (both p < 0.001). All TEG values, as well as CAT lag time, thrombin potential, and peak thrombin were more hypercoagulable in the green plasma group compared to standard‐color female and male donor units; all p < 0.05. In addition, the majority of factor levels (including II, VII, IX, X, and fibrinogen) were higher in green donor plasma; all p < 0.05. Discussion: Based on our data, green plasma has superior hemostatic potential without any other aberrant characteristics, possibly justifying the use of green plasma in transfusion medicine. Reintroducing this product will help to expand on the plasma donor pool.

Background: Best practice guidelines from trauma-focused organizations support early (<72 hours) venous thromboembolism (VTE) chemoprophylaxis initiation in traumatic brain injury (TBI) patients. Recent literature suggests that an even more aggressive initiation (24 hours) is safe and efficacious. It is unknown how current practice aligns with the existing literature and best practice guidelines. We performed a national survey to characterize variation in trauma surgeons’ reported practices and attitudes regarding VTE chemoprophylaxis initiation in TBI patients with the hypothesis that they will vary widely. Methods: All 1700 American Association for the Surgery of Trauma members were surveyed online. Members who routinely cared for patients with TBI were asked to proceed with the survey. Descriptive data were reported. The questions characterized institutional guidelines, and if none existed, individual practice patterns regarding goal timeline of VTE chemoprophylaxis in TBI patients. Results: 374 members (22%) completed the survey. Most respondents worked at academic institutions (40%) and represented a level one trauma center (44%). Enoxaparin was the most common VTE chemoprophylactic (73%) with most using weight-based dosing (76%) and anti-Xa testing (75%). Institutional policies that included a protocol for VTE chemoprophylaxis initiation in TBI patients were used by 86% of respondents. In those with established protocols, 59% reported being mostly compliant. Reasons for delay of VTE chemoprophylaxis included worry about progression of TBI and disagreement with consulting services. 293 (80%) of respondents reported protocolized repeat head CT within 4–12 hours after initial CT (60%). In response to a clinical scenario, 43% of respondents reported that their goal timeline for initiating VTE prophylaxis was within 24 hours of a stable head CT. Conclusions: Despite national guidelines, substantial variation remains in the timing of VTE chemoprophylaxis in TBI patients. Passive strategies, such as institutional guidelines alone, are insufficient. Institutions must adopt more effective implementation tactics—including protocol-enforced order sets, automated clinical decision support, and shared governance models with ancillary services—to ensure timely, evidence-based care. Level of evidence: Level V.

Hemorrhage is the leading cause of preventable death on the battlefield, yet combat medics lack clinical decision support systems to help stratify hemorrhage risk in trauma casualties. We previously trained the Automated Processing of the Physiological Registry for Assessment of Injury Severity — Hemorrhage Risk Index (APPRAISE-HRI) software to associate patterns in vital signs (heart rate and blood pressure) collected from trauma patients with three HRI levels: I (low), II (average), or III (high). To independently validate APPRAISE-HRI and obtain U.S. Food and Drug Administration (FDA) clearance, we collected trauma registry and continuous vital sign data from 5895 trauma patients (543 with hemorrhagic injuries and 5352 controls) in an emergency department or during prehospital transport to one of eight medical centers. The study outcome was hemorrhagic injury, defined by documented injuries and blood transfusion. Using the likelihood ratio to assess the ability of APPRAISE-HRI to stratify hemorrhage risk, we found that hemorrhagic patients were 6.88 times as likely as controls to be at level III, strongly suggesting the presence of hemorrhage at this level. Similarly, hemorrhagic patients were 0.18 times as likely as controls to be at level I, suggesting the absence of hemorrhage at this level. Hemorrhagic patients were almost as likely as controls to be at level II (0.70 times as likely). Subsequently, the U.S. Department of Defense obtained FDA 510(k) clearance for the artificial intelligence–enabled APPRAISE-HRI Class II device (K233249), the first software as a medical device approved for assessing hemorrhage risk in trauma patients, allowing for triage and identification of casualties who need immediate attention and evacuation. (Funded by the U.S. Army Medical Materiel Development Activity and the Combat Casualty Care Program Area Directorate (CCCPAD) of the U.S. Army Medical Research and Development Command (USAMRDC), Fort Detrick, MD and others.)