Immune and Inflammatory Predictors of Massive Transfusion and Clinical Outcomes in Patients with Severe Trauma
-
Mao Ye
,
Wenzhao Hu
,
Chen Qin
,
Yue Wu
,
Xing Wu
Abstract
Massive blood transfusion (MBT) in severe trauma represents a major emergency-care challenge associated with high mortality and poor clinical outcomes. This retrospective cohort study enrolled 186 severe trauma patients treated at Xianning Central Hospital from January 2020 to January 2024, who were stratified into massive blood transfusion (MBT, ≥10 units RBCs within 24 h, n=72) and non-MBT (n=114) groups.
The observed indicators included immune markers CD4+:CD8+ ratio, natural killer (NK) cells, immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM); inflammatory markers white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6); trauma severity assessment indicators Injury Severity Score (ISS) and modified Trauma Induced Coagulopathy Clinical Score (mTICCS); and clinical events including transfusion adverse events and mechanical ventilation duration. Logistic regression identified independent MBT predictors; receiver operating characteristic (ROC) curves evaluated their predictive performance.
The two groups showed comparable baseline characteristics. The MBT group presented a lower CD4+/CD8+ ratio, higher NLR, inflammatory factors, ISS and mTICCS, as well as more transfusion adverse events and longer ventilation duration. NLR ≥ 9.5, CD4+/CD8+ ≤ 0.7, ISS ≥ 25, and mTICCS ≥ 12 were independent MBT predictors. ROC analysis revealed favorable predictive performance for these indicators, with the highest AUC of 0.810 for mTICCS, followed by NLR (0.806) and CD4+:CD8+ ratio (0.800), with no significant predictive differences among them via DeLong test.
This study demonstrates that admission immune-inflammatory status and trauma severity are reliable early biomarkers for predicting MBT in severe trauma patients.
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15. Chen XY, Liu HS, Xiang Q, Liu SQ, Liu MH, Zhao XD, et al. Chinese Consensus Statement on Traumatic Hemorrhagic Shock in Emergency Medicine (2023). Chin J Emerg Med. 2023; 43(11):841-54.
16. Zheng S, Zhang W. Predictive Values of sTREM-1, PCT and CRP for Multiple Trauma-Induced Acute Respiratory Distress Syndrome Complicated with Pulmonary Infection. Clin Lab. 2022; 68(12)
17. Laajimi S, Bhiri S, Chebbi N, Bradai H, Belkhiria A, Loghmari D, Chebili N, Mbarek R, Kahloul M. Assessment of the correlation between the Vittel criteria and the ISS score: A novel approach to pre-hospital severe trauma patient's triage. Tunis Med. 2024; 102(12):1055-61.
18. Horst K, Lichte P, Blasius F, Weber CD, Tonglet M, Kobbe P, Heussen N, Hildebrand F. mTICCS and its inter-rater reliability to predict the need for massive transfusion in severely injured patients. Eur J Trauma Emerg Surg. 2022; 48(1):367-72.
19. Bouzat P, Charbit J, Abback PS, Huet-Garrigue D, Delhaye N, Leone M, et al. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial. JAMA. 2023; 329(16):1367-75.
20. Gilaed A, Shorbaji N, Katzir O, Ankol S, Badarni K, Andrawus E, et al. Early risk factors for prolonged mechanical ventilation in patients with severe blunt thoracic trauma: A retrospective cohort study. Injury. 2024; 55(1):111194.
21. World Medical A. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025; 333(1):71-4.
22. National Health Commission. Notice on Issuing the Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects. Accessed 2025-12-26, https://www.gov.cn/zhengce/zhengceku/2023-02/28/content_5743658.htm
23. El-Menyar A, Mekkodathil A, Al-Ansari A, Asim M, Elmenyar E, Rizoli S, et al. Platelet-Lymphocyte and Neutrophil-Lymphocyte Ratio for Prediction of Hospital Outcomes in Patients with Abdominal Trauma. Biomed Res Int. 2022; 2022:5374419.
24. Holmberg L, Mani K, Thorbjornsen K, Wanhainen A, Andreasson H, Juhlin C, et al. Trauma triage criteria as predictors of severe injury - a Swedish multicenter cohort study. BMC Emerg Med. 2022; 22(1):40.
25. Hardy BM, Enninghorst N, Balogh ZJ. Injury severity-based discrepancies in severe trauma survival improvement. Eur J Trauma Emerg Surg. 2025; 51(1):280.
26. Kong Z, Cai S, Xie W, Chen J, Xie J, Yang F, et al CD4 + T cells ferroptosis is associated with the development of sepsis in severe polytrauma patients. Int Immunopharmacol. 2024; 127:111377.
27. Tiwari-Heckler S, Lee GR, Harbison J, Ledderose C, Csizmadia E, Melton D, et al. Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39. Thorax. 2023; 78(2):151-59.
28. Bansal N, Raturi M, Singh C, Bansal Y. Immunological complications of blood transfusion: current insights and advances. Curr Opin Immunol. 2025; 96:102617.
29. Yan S, Lu B, Li M, Li J, Li N. The value of serum PCT/ALB and CRP/ALB ratios in evaluating the condition and prognosis of craniocerebral trauma. Folia Neuropathol. 2024; 62(2):187-96.
30. Baucom MR, Wallen TE, Price AD, Smith MP, Kopchak M, MacKinnon A, et al. Predictive Value of Early Inflammatory Markers in Trauma Patients Based on Transfusion Status. Journal of Surgical Research. 2023; 291:691-99.
31. Pandurangan AK. Targeting IL-17A: A New Frontier in the Treatment of Colitis-Associated Cancer. Curr Cancer Res. 2025; 1(1):16-24.
32. Peng C, Zhu R, Yang F, Guo Y, Li L, Jin Z, Wu C, Xu S. High whole blood to total transfusion volume ratio and survival outcomes in patients with trauma requiring massive transfusions. Emerg Med J. 2025; 42(10):669-75.
33. Liu XY, Qin YM, Tian SF, Zhou JH, Wu Q, et al. Performance of trauma scoring systems in predicting mortality in geriatric trauma patients: comparison of the ISS, TRISS, and GTOS based on a systemic review and meta-analysis. Eur J Trauma Emerg Surg. 2024; 50(4):1453-65.
34. Hall C, Nagengast AK, Knapp C, Behrens B, Dewey EN, Goodman A, Bommiasamy A, Schreiber M. Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines. Transfusion. 2021; 61 Suppl 1:S188-S94.
35. Li R, Han W, Lu J, Sun X, Tang T. The predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting. Eur J Trauma Emerg Surg. 2024; 50(3):967-73.
2. Roshanaei G, Khoshravesh S, Abdolmaleki S, Bathaei T, Farzian M, Saatian M. Epidemiological pattern of trauma patients based on the mechanisms of trauma: trends of a regional trauma center in Midwest of Iran. BMC Emerg Med. 2022; 22(1):210.
3. Marcos-Morales A, Barea Mendoza JA, Valiente Fernandez M, Garcia Fuentes C, Calvo Boyero F, Cueto-Felgueroso C, et al. Key laboratory changes in severe trauma, a different pattern for each clinical phenotype. Med Intensiva (Engl Ed). 2025:502227.
4. Mitra B, Singh B, Mathew J, Stewart C, Koolstra C, Hendel S, et al. Timing and volume of transfusion for adult major trauma patients with hemorrhagic shock: a registry-based cohort study. Trauma Surg Acute Care Open. 2024; 9(1):e001248.
5. Rayatdoost F, Kapur R. Transfusion-related acute lung injury: experimental models to study pathogenesis and therapeutic strategies. Curr Opin Immunol. 2025; 96:102650.
6. Lin TL, Liu HT, Hsieh CH. Current controversies and advances in massive transfusion: Balancing evidence and practice. Journal of the Formosan Medical Association. 2025;
7. Lauten TH, Natour T, Case AJ. Innate and adaptive immune system consequences of post-traumatic stress disorder. Autonomic Neuroscience. 2024; 252:103159.
8. Li R, Ye JJ, Gan L, Zhang M, Sun D, Li Y, Wang T, Chang P. Traumatic inflammatory response: pathophysiological role and clinical value of cytokines. Eur J Trauma Emerg Surg. 2024; 50(4):1313-30.
9. Li M, Qin YJ, Zhang XL, Zhang CH, Ci RJ, Chen W, Hu DZ, Dong SM. A biomarker panel of C-reactive protein, procalcitonin and serum amyloid A is a predictor of sepsis in severe trauma patients. Sci Rep. 2024; 14(1):628.
10. Yang YW, Wu CH, Tsai HT, Chen YR, Chang YP, Han YY, et al. Dynamics of immune responses are inconsistent when trauma patients are grouped by injury severity score and clinical outcomes. Sci Rep. 2023; 13(1):1391.
11. Mondello S, Amrein K, Czeiter E, Citerio G, Diaz-Arrastia R, Gao G, et al. Prognostic Value of Blood-Based Protein Biomarkers in Traumatic Brain Injury: A Living Systematic Review and Meta-Analysis. J Neurotrauma. 2025; 42(15-16):1256-86.
12. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021; 122(7):474-88.
13. Colnaric JM, El Sibai RH, Bachir RH, El Sayed MJ. Injury severity score as a predictor of mortality in adult trauma patients by injury mechanism types in the United States: A retrospective observational study. Medicine (Baltimore). 2022; 101(28):e29614.
14. Jin H, Zhang Y, Zhang Q, Ouyang L, Li X, Zhang Y, et al. Comparison of Injury Severity Score (ISS) and New Injury Severity Score (NISS) in the Evaluation of Thoracic Trauma Patients: A Retrospective Cohort Study. Emerg Med Int. 2024; 2024:4861308.
15. Chen XY, Liu HS, Xiang Q, Liu SQ, Liu MH, Zhao XD, et al. Chinese Consensus Statement on Traumatic Hemorrhagic Shock in Emergency Medicine (2023). Chin J Emerg Med. 2023; 43(11):841-54.
16. Zheng S, Zhang W. Predictive Values of sTREM-1, PCT and CRP for Multiple Trauma-Induced Acute Respiratory Distress Syndrome Complicated with Pulmonary Infection. Clin Lab. 2022; 68(12)
17. Laajimi S, Bhiri S, Chebbi N, Bradai H, Belkhiria A, Loghmari D, Chebili N, Mbarek R, Kahloul M. Assessment of the correlation between the Vittel criteria and the ISS score: A novel approach to pre-hospital severe trauma patient's triage. Tunis Med. 2024; 102(12):1055-61.
18. Horst K, Lichte P, Blasius F, Weber CD, Tonglet M, Kobbe P, Heussen N, Hildebrand F. mTICCS and its inter-rater reliability to predict the need for massive transfusion in severely injured patients. Eur J Trauma Emerg Surg. 2022; 48(1):367-72.
19. Bouzat P, Charbit J, Abback PS, Huet-Garrigue D, Delhaye N, Leone M, et al. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial. JAMA. 2023; 329(16):1367-75.
20. Gilaed A, Shorbaji N, Katzir O, Ankol S, Badarni K, Andrawus E, et al. Early risk factors for prolonged mechanical ventilation in patients with severe blunt thoracic trauma: A retrospective cohort study. Injury. 2024; 55(1):111194.
21. World Medical A. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA. 2025; 333(1):71-4.
22. National Health Commission. Notice on Issuing the Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects. Accessed 2025-12-26, https://www.gov.cn/zhengce/zhengceku/2023-02/28/content_5743658.htm
23. El-Menyar A, Mekkodathil A, Al-Ansari A, Asim M, Elmenyar E, Rizoli S, et al. Platelet-Lymphocyte and Neutrophil-Lymphocyte Ratio for Prediction of Hospital Outcomes in Patients with Abdominal Trauma. Biomed Res Int. 2022; 2022:5374419.
24. Holmberg L, Mani K, Thorbjornsen K, Wanhainen A, Andreasson H, Juhlin C, et al. Trauma triage criteria as predictors of severe injury - a Swedish multicenter cohort study. BMC Emerg Med. 2022; 22(1):40.
25. Hardy BM, Enninghorst N, Balogh ZJ. Injury severity-based discrepancies in severe trauma survival improvement. Eur J Trauma Emerg Surg. 2025; 51(1):280.
26. Kong Z, Cai S, Xie W, Chen J, Xie J, Yang F, et al CD4 + T cells ferroptosis is associated with the development of sepsis in severe polytrauma patients. Int Immunopharmacol. 2024; 127:111377.
27. Tiwari-Heckler S, Lee GR, Harbison J, Ledderose C, Csizmadia E, Melton D, et al. Extracellular mitochondria drive CD8 T cell dysfunction in trauma by upregulating CD39. Thorax. 2023; 78(2):151-59.
28. Bansal N, Raturi M, Singh C, Bansal Y. Immunological complications of blood transfusion: current insights and advances. Curr Opin Immunol. 2025; 96:102617.
29. Yan S, Lu B, Li M, Li J, Li N. The value of serum PCT/ALB and CRP/ALB ratios in evaluating the condition and prognosis of craniocerebral trauma. Folia Neuropathol. 2024; 62(2):187-96.
30. Baucom MR, Wallen TE, Price AD, Smith MP, Kopchak M, MacKinnon A, et al. Predictive Value of Early Inflammatory Markers in Trauma Patients Based on Transfusion Status. Journal of Surgical Research. 2023; 291:691-99.
31. Pandurangan AK. Targeting IL-17A: A New Frontier in the Treatment of Colitis-Associated Cancer. Curr Cancer Res. 2025; 1(1):16-24.
32. Peng C, Zhu R, Yang F, Guo Y, Li L, Jin Z, Wu C, Xu S. High whole blood to total transfusion volume ratio and survival outcomes in patients with trauma requiring massive transfusions. Emerg Med J. 2025; 42(10):669-75.
33. Liu XY, Qin YM, Tian SF, Zhou JH, Wu Q, et al. Performance of trauma scoring systems in predicting mortality in geriatric trauma patients: comparison of the ISS, TRISS, and GTOS based on a systemic review and meta-analysis. Eur J Trauma Emerg Surg. 2024; 50(4):1453-65.
34. Hall C, Nagengast AK, Knapp C, Behrens B, Dewey EN, Goodman A, Bommiasamy A, Schreiber M. Massive transfusions and severe hypocalcemia: An opportunity for monitoring and supplementation guidelines. Transfusion. 2021; 61 Suppl 1:S188-S94.
35. Li R, Han W, Lu J, Sun X, Tang T. The predictive value of four traumatic hemorrhage scores for early massive blood transfusion in trauma patients in the pre-hospital setting. Eur J Trauma Emerg Surg. 2024; 50(3):967-73.
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How to Cite
1.
Ye M, Hu W, Qin C, Wu Y, Wu X. Immune and Inflammatory Predictors of Massive Transfusion and Clinical Outcomes in Patients with Severe Trauma. Iran J Allergy Asthma Immunol. 2026;:1-15.
