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Open research questions in Trauma, Hemostasis, Coagulopathy, Resuscitation

38 unresolved questions extracted from the limitations and future-work sections of 253 Trauma, Hemostasis, Coagulopathy, Resuscitation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Whole blood remains an active area of investigation in trauma resuscitation. Although recent randomized trials have not demonstrated clear superiority over balanced com- ponent therapy, the growing body of evidence suggests a meaningful benefit in select patient populations, particularly in civilian settings and in penetrating trauma. Whole blood is not a singular solution to traumatic hemorrhage but rather one component of a multifaceted resuscitation strategy. Nev- ertheless, it continues to demonstrate a positive role through reduced transfusion requirements and logistical advantages over component therapy. For these reasons it may also be an attractive option in patients with non-traumatic bleeding as well, including fields like obstetrics, critical care, and trans- plant. As our understanding of the immunological effects of blood product transfusion deepens, and as evidence accu- mulates in specific populations such as obstetric and pedi- atric patients, the role of whole blood will continue to be refined. Advances in donor screening and cold-stored whole blood programs may further expand its availability beyond major trauma centers to community and rural hospitals, and potentially beyond trauma altogether to other clinical settings where acute hemorrhage demands rapid, balanced resuscitation.

    Current Clinical Implications of Whole Blood in Trauma Resuscitation · 2026 · DOI

  • Future research should focus on prospective field validation of the proposed algorithm in contemporary conflicts, assessment of logistical considerations (shelf life and cost), and the development of hybrid devices combining the volumetric effect of XStat with the com- plete biodegradability of chitosan-based materials.

    Comparative Study of Haemostatic Agents in Tactical Environments and Their Impact on Survival Time before Evacuation · 2026 · DOI

  • Objectives: Epistaxis is a common emergency department (ED) presentation, but the prognostic significance of triage blood pressure (BP) remains unclear.

    Association Between Systolic Blood Pressure at Emergency Department Arrival and Time to Bleeding Cessation in Adult Non-Traumatic Epistaxis: A Retrospective Time-to-Event Analysis · 2026 · DOI

  • This temporal dis- sociation indicates that impaired macrocirculatory param- eters alone were insufficient to trigger detectable membrane phospholipid degradation under the conditions of this experiment [44–46].

    Cerebral glycerol during haemorrhagic shock in normal and raised intracranial pressure resuscitated with total REBOA: an experimental porcine study · 2026 · DOI

  • Nevertheless, further research is required to determine the reliability, ethical implications, and operational feasibility of artificial intelligence in combat environments. Long-term neuropsychological outcomes remain incompletely understood, particularly among individuals exposed to repetitive blast exposure.

    Advances in Tactical Combat Casualty Care: Contemporary Strategies for Hemorrhage Control, Neurotrauma Management, and Multidisciplinary Recovery in Modern Warfare · 2026 · DOI

  • The findings support individualized use of plasma and platelets in GI haemorrhage rather than reflexive application of the 1:1:1 trauma protocol; prospective confirmation is warranted.

    Non-inferiority of a red-blood-cell--only transfusion strategy compared with balanced resuscitation in adults with massive gastrointestinal haemorrhage: a propensity-score-weighted cohort study · 2026 · DOI

  • BACKGROUND Patients undergoing liver transplantation often develop multiple hemostatic abnormalities requiring dynamic transfusion and antifibrinolytic support; however, how hemostatic status changes over time during liver transplant surgery is not well defined, limiting clinicians’ ability to anticipate and manage hemostatic instability.

    Thromboelastographic description of intraoperative coagulopathy in patients undergoing liver transplant surgery: A single-center observational study · 2026 · DOI

  • This LPS model induces endotoxemia and simplifies sec- ondary hematological and hemostatic reactions. How- ever, it lacks two key features of human sepsis: bacterial dissemination and immune adaptation. Thus, further research is needed before H12-(ADP)-liposomes can be used to treat septic shock in humans. There is a discrepancy between the number of enrolled animals and the number of blood samples. This dis- crepancy is associated with the difficulty in obtaining sufficient amounts of blood samples for ELISA due to hypovolemia induced by LPS administration. The Syndecan-1 levels fall in the LPS + vehicle group after 24 h compared to 12 h without any treatment might be due to survival bias. In brief, the animals with severely elevated Syndecan-1 had more endothelial damage and were dead, so blood samples were unavailable. In this study, direct attachment of H12-(ADP)- liposomes to PLA was only detected by ultrastructural examination. Future studies using confocal micros- copy with fluorescent staining dyes will help elucidate the detailed functional relationship between PLA and H12-(ADP)-liposomes. There were no findings of side effects of H12-(ADP)- liposomes such as thrombosis in this cohort, along with our previous studies. However, these liposomes may exacerbate ongoing thrombus formation in cases that have unstable coronary atherothrombotic plaques with highly activated platelets. We used H12-(ADP)-liposomes for single bolus admin- istration in our previous studies, because this agent was developed for prehospital treatment. If a single dose is insufficient, repeated dosing may be administered every 12 h based on the liposome half-life. As part of normal sepsis treatment, no volume was administered intra- venously after LPS stimulation, except for H12-(ADP)- liposomes or the vehicle. However, the administration of a crystalloid infusion as part of standard sepsis treatment could significantly impact coagulation and endothelial dysfunction.

    Post-treatment with H12-(ADP)-liposomes after LPS challenge ameliorated coagulopathy and critical organ injury in rats · 2026 · DOI

  • Critical evidence gaps remain. Future work should prioritize: 1. large, prospective neuro-specific cohorts using standardized viscoelastic thresholds. 2. randomized trials evaluating VHA-guided transfusion or reversal strategies in TBI and SAH. 3. harmonization of assay parameters and clinical definitions. 4. mechanistic studies linking VHA abnormalities with neurovascular pathophysiology. 5. and targeted evaluation of TEG-guided antiplatelet therapy in stroke populations.

    The utility of viscoelastic hemostatic assays in neurocritical illness · 2026 · DOI

  • This study has several limitations. First, we retrospectively defined massive transfusion within 24 h of injury; therefore, the study population may differ from other definitions used to evaluate high PC strategies. Second, selection bias between the high- and low-PC groups is possible, as patients who survived initial resuscita- tion may have received higher PC-to-RBC ratios. Although time-dependent analysis would better address this issue, data on transfusion timing were unavailable. We performed sensitivity analyses excluding emergency department deaths and patients without PC transfusion to assess robustness; however, residual bias cannot be excluded. Third, as a retrospective observational study, unmeasured confounding is inevitable. In particular, TXA administra- tion was not fully protocolized during the study period and depended on physician discretion, which may have influ- enced outcomes. Fourth, external validity may be limited. Platelet units in Japan generally contain fewer platelets than standard apheresis units used in the United States and Europe (approximately 3–4 × 10¹¹ platelets per dose) [30], and thus equivalent PC-to-RBC ratios may not represent comparable absolute platelet doses. Fifth, cause-specific mortality and detailed neurological data were unavailable. Mortality in massively transfused patients may also be influenced by intracranial hemorrhage and neurological deterioration. Although improved in-hos- pital survival was also observed in the high PC group, the impact of transfusion strategy on neurological outcomes remains uncertain. M. Aoki et al.1 3 Page 9 of 10 134 the chest, abdomen or pelvis, AIS for the head/neck, chest, abdomen, and pelvis/lower extremity, ISS and administration of tranexamic acid, with a ratio of 1 as a reference. PC, platelet concentrate; RBC, red blood cell; FFP, fresh frozen plasma; CCI, charlson comorbidity index; CT, computed tomography; AIS, abbreviated injury scale; ISS, injury severity score Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request.

    Association between high ratio of platelet concentrate to red blood cell and survival among massively transfused patients · 2026 · DOI

  • Variations in study design (such as platelet activation, FXIII availability, and whether clot contraction is preserved during testing) may explain conflicting findings about fibrin network structure under cold storage across different studies.

    Effects of leukoreduction and storage duration on whole blood hemostatic function: a prospective ex vivo observational study · 2026 · DOI

  • Clinical 'acceptability' thresholds were not defined a priori; the 7–14-day transfusion window referenced in some programs reflects prior practice rather than a recommendation derived from the dataset.

    Effects of leukoreduction and storage duration on whole blood hemostatic function: a prospective ex vivo observational study · 2026 · DOI

  • The 3-hour window was deduced from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial and has not been replicated.

    Tranexamic Acid Timing and Mortality Impact After Trauma · 2025 · DOI

  • Although, data regarding TXA implementation in prehospital trauma care are lacking, the most recent European Trauma Bleeding Guidelines recommend using TXA en route to the hospital.

    Prehospital use of tranexamic acid for damage- control resuscitation in polytraumatised patients · 2015

  • 2When presented with trauma situations where massive external bleeding cannot be controlled by direct pressure and/or with the use of a tourniquet (ie, hemorrhaging occurring in sites not amenable to tourniquet placement such as the abdomen, groin, or chest), the application of a topical hemostatic agent is warranted.

    Educating the Educator: Use of Advanced Bleeding Control Mechanisms in Athletic Training: A Shift in the Thought Process of Prehospital Care—Part 2: Hemostatic Agents · 2014 · DOI

  • Furosemide in continuous perfusion was not associated with a significant reduction in risk of hospital mortality as compared to bolus administration in critically ill patients in ICU, but existing data are insufficient to confidently assess the best way to administer furosemide .

    Continuous infusion versus bolus injection of furosemide in critically ill patients.A systematic review and meta-analysis · 2011 · DOI

  • Rehabilitation was not limited to the period after definitive surgery. The effectiveness of prophylaxis varied across infection outcomes, and the certainty of review-level evidence was limited (3).

    <b>Systematic Review of Medical Optimisation of Polytrauma Patients Undergoing Surgery</b> · 2026 · DOI

  • Despite its frequency and potential severity, perioperative PIV infiltration remains inconsistently reported and understudied.

    Perioperative Intravenous Infiltration: From Recognition to Prevention · 2026 · DOI

  • Although a fixed formal review interval has not yet been established, protocol revisions are performed as needed based on post-event review, simulation findings, and changes in local operating room workflows.

    Development and Clinical Deployment of the Systematic Urgent Team Response in the Operating Room (SUTO) Protocol for Intraoperative Massive Hemorrhage: A Technical Report · 2026 · DOI

  • These findings highlight the potential of using these readily available admission parameters for early risk stratification and targeted coagulation management, though large-scale prospective vali- dation is warranted prior to routine clinical implementation.

    Risk factors and preliminary prediction models for trauma-induced coagulopathy and 28-day mortality in severely injured patients: a retrospective observational cohort study · 2026 · DOI

  • In addition, future studies are needed to characterize the stoichiometric relationship between SkM and fibrin and to assess how varying SkM-to-fibrinogen ratios affect clot formation and stability.

    Characterization of the binding of skeletal muscle myosin to fibrin in trauma · 2026 · DOI

  • Only a single leukoreduction workflow was evaluated (a standard, non–platelet-sparing filter applied under a specific protocol), so applicability to platelet-sparing filters, alternative devices, or different leukoreduction timing remains uncertain.

    Effects of leukoreduction and storage duration on whole blood hemostatic function: a prospective ex vivo observational study · 2026 · DOI

  • This was an ex vivo, paired-unit study with a limited number of whole-blood units; therefore, the findings characterize product-level changes and cannot be directly extrapolated to patient outcomes.

    Effects of leukoreduction and storage duration on whole blood hemostatic function: a prospective ex vivo observational study · 2026 · DOI

  • While previous research shows simple JiT instructions boost laypeople's success with tourniquet application, the optimal approach to educate the public is not yet known.

    Brief, Web‐based Education Improves Lay Rescuer Application of a Tourniquet to Control Life‐threatening Bleeding · 2018 · DOI

  • When continuous direct/manual pressure is warranted to provide additional care, a pressure bandage (elastic or roller bandage) firmly applied over the dressing may be utilized.

    Educating the Educator: Use of Advanced Bleeding Control Mechanisms in Athletic Training: A Shift in the Thought Process of Prehospital Care—Part 2: Hemostatic Agents · 2014 · DOI

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38 open questions have been extracted from the limitations and future-work passages of 253 Trauma, Hemostasis, Coagulopathy, Resuscitation papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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