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Open research questions in Trauma, Hemostasis, Coagulopathy, Resuscitation

93 unresolved questions extracted from the limitations and future-work sections of 370 Trauma, Hemostasis, Coagulopathy, Resuscitation papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • These findings should be interpreted in the context of the outcome-specific certainty of evidence, the limited evidence base, and clinical and statistical heterogeneity across studies.

    Systematic literature review and meta-analysis on the safety of fibrinogen concentrate versus cryoprecipitate in patients with surgical bleeding · 2026 · DOI

  • Background: Composite biomarkers combining inflammatory or metabolic markers with a negative acute-phase protein predict outcomes in critically ill patients, but fibrinogen-based ratios grounded in the “lethal triad” of trauma-induced coagulopathy remain unexplored in pediatric trauma.

    Novel Fibrinogen- and Procalcitonin-Based Composite Ratios for Mortality Prediction in Pediatric Trauma · 2026 · DOI

  • As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended.

    Albumin Replacement Therapy in Septic Shock · 2026 · DOI

  • BACKGROUND: The coagulation system is closely linked to the inflammatory response and kinin system activation in sepsis, but its contribution to sepsis-associated capillary leak syndrome (SACLS) remains elusive.

    Capillary leak syndrome in sepsis: the role of intrinsic coagulation pathway activation · 2025 · DOI

  • Despite lacking data, young donor plasma infusions have been promoted for age-related conditions.

    Infusion of young donor plasma components in older patients modifies the immune and inflammatory response to surgical tissue injury: a randomized clinical trial · 2025 · DOI

  • The underlying causes of post-CPB coagulopathy and the factors associated with its occurrence are not yet fully understood.

    Quantitative and functional changes in platelets and fibrinogen following cardiopulmonary by-pass in children · 2024 · DOI

  • However, the underlying mechanisms linking endothelial glycocalyx damage to dietary salt and HIV infection are lacking.

    High salt intake and HIV infection on endothelial glycocalyx shedding in salt-sensitive hypertension · 2024 · DOI

  • Importance: Although major bleeding is among the most common and prognostically important perioperative complications, the relative timing of bleeding events is not well established.

    Timing of Major Postoperative Bleeding Among Patients Undergoing Surgery · 2024 · DOI

  • These trials used generalized approaches to resuscitation, and little is known about how clinicians personalize fluid and vasopressor administration in practice.

    Understanding How Clinicians Personalize Fluid and Vasopressor Decisions in Early Sepsis Management · 2024 · DOI

  • The study is limited to a single ex vivo whole-blood cohort without external validation or replication. The study does not provide definitive proof of causal pathways.

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

  • The effects of leukoreduction on whole blood hemostatic function are not well understood. There is a need for studies that investigate the effects of leukoreduction on whole blood hemostatic function.

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

  • The impact of a higher PC: RBC ratio on survival remains unclear. There is a need to investigate the effectiveness of a high PC to RBC ratio among severely injured patients requiring massive transfusion.

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

  • The effect of intravenous fluid administration rate on glycocalyx integrity is unclear. There is a need for studies to examine the effect of fluid administration rate on glycocalyx integrity in septic patients.

    Speed of intravenous fluid on glycocalyx integrity and central blood volume in a porcine septic shock model · 2026 · DOI

  • The evidence base is dominated by observational studies. Randomized trial data are limited. The review is restricted to systematic reviews with reproducible methods and extractable neuro-specific VHA data.

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

  • The clinical value of viscoelastic hemostatic assays in neurocritical illness remains uncertain. Evidence for VHA-guided intervention in TBI or SAH remains insufficient. The review highlights the need for further research on the utility of VHAs in neurocritical care.

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

  • The lack of reliable early warning indicators for TIC. The need for robust prediction models for TIC and mortality.

    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

  • Septic shock often causes coagulopathy involving excessively activated platelets. Activated platelets synergistically interact with neutrophils to form neutrophil extracellular traps (NETs) at injured endothelium. Comprehensive, specific, and effective treatments for consumptive coagulopathy have yet to be established.

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

  • Further studies are needed to investigate the mechanisms by which H12-(ADP)-liposomes exert their effects. Additional research is required to determine the optimal dosage and administration schedule for H12-(ADP)-liposomes. Future studies should evaluate the efficacy of H12-(ADP)-liposomes in human subjects.

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

  • The association of pre-operative anaemia with survival after liver transplantation is uncertain. It is unclear whether pre-operative anaemia is associated with outcome after liver transplantation.

    Blood conservation strategies in liver transplantation: Past, present, and future · 2026 · DOI

  • The study does not report on the temperature control during transport. The study has a limited sample size of 46 healthy volunteers and 45 septic patients.

    Effects of pneumatic tube systems on next-generation viscoelastic coagulation test devices in septic patients and healthy individuals: Results of the randomized controlled VETaPT trial · 2026 · DOI

  • The study identifies a gap in the literature regarding the effects of pneumatic tube systems on next-generation viscoelastic coagulation test devices. The study addresses the need for quantitative analysis of acceleration forces during transport.

    Effects of pneumatic tube systems on next-generation viscoelastic coagulation test devices in septic patients and healthy individuals: Results of the randomized controlled VETaPT trial · 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

  • 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

  • Development of standardized endpoints for microcirculatory assessment, - Investigation of cardioprotective strategies to preserve microcirculatory function during CPB, - Elucidation of the mechanisms by which CPB impairs microvascular function

    Microcirculation dysfunction and cardioprotection in cardiac surgery with cardiopulmonary bypass: mechanisms, monitoring, and therapeutic strategies · 2026 · DOI

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93 open questions have been extracted from the limitations and future-work passages of 370 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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