[2026-11-02] Brain Thromboplastin, Biomarkers, and Coagulograms in Traumatic Brain Injury: Translating Pathophysiology Into Point-of-Care Practice

Supanadee Jianwittayakit; Krongthip Sripunjan; Alisa Amornkornkijkul; Phongthara Vichitvejpaisal

doi:10.33165/rmj.2028.e279916

Authors

Supanadee Jianwittayakit Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand https://orcid.org/0009-0008-9390-4856
Krongthip Sripunjan Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0001-8794-8838
Alisa Amornkornkijkul Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand https://orcid.org/0009-0003-4510-7880
Phongthara Vichitvejpaisal Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand https://orcid.org/0000-0003-2656-6718

DOI:

https://doi.org/10.33165/rmj.2028.e279916

Keywords:

Brain thromboplastin, Tissue factor, Biomarkers, Coagulopathy, Traumatic brain injury, Viscoelastic testing

Abstract

Traumatic brain injury (TBI) is a leading cause of global morbidity and mortality, often complicated by coagulopathy. This narrative review explores how hemostatic disruption drives hemorrhagic progression or thromboembolic events, making early intervention crucial. A central mechanism is the release of tissue factor (TF), brain thromboplastin, from damaged neural tissue, which activates the extrinsic coagulation pathway to create a dynamic state of hypercoagulability, hypocoagulability, and fibrinolysis. These disturbances are further amplified by endothelial injury and brain-derived microparticles. While standard coagulograms and conventional biomarkers provide useful baselines, they lack TBI specificity and fail to capture evolving clot dynamics. Emerging biomarkers such as glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 offer targeted early risk assessment, while viscoelastic testing provides
real-time, functional evaluation of clot formation and lysis. Integrating these novel biomarkers with viscoelastic methods may help guide precise, goal-directed transfusion strategies. Future research must prioritize validating biomarker-driven algorithms, testing-guided therapies, and the targeted modulation of the TF pathway to optimize patient care

References

1. Rubiano AM, Griswold DP, Jibaja M, Rabinstein AA, Godoy DA. Management of severe traumatic brain injury in regions with limited resources. Brain Inj. 2021;35(11):1317-1325. doi:10.1080/02699052.2021.1972149

2. Demir Y, Köroğlu Ö, Tekin E, et al. Factors affecting functional outcome in patients with traumatic brain injury sequelae: our single-center experiences on brain injury rehabilitation. Turk J Phys Med Rehabil. 2018;65(1):67-73. doi:10.5606/tftrd.2019.2281

3. Khellaf A, Khan DZ, Helmy A. Recent advances in traumatic brain injury. J Neurol. 2019;266:2878-2889. doi:10.1007/s00415-019-09541-4

4. Hou H, Qu Z, Liu R, Jiang B, Wang L, Li A. Traumatic brain injury: advances in coagulopathy (review). Biomed Rep. 2024;21(5):156. doi:10.3892/br.2024.1844

5. Fletcher-Sandersjöö A, Sebghati J, Thelin EP. Hemostatic disturbances in traumatic brain injury: from mechanism to management. Acta Neurochir. 2025;167(1):146. doi:10.1007/s00701-025-06549-w

6. Bradbury JL, Thomas SG, Sorg NR, et al. Viscoelastic testing and coagulopathy of traumatic brain injury. J Clin Med. 2021;10(21):5039. doi:10.3390/jcm10215039

7. Wada T, Shiraishi A, Gando S, et al. Pathophysiology of coagulopathy induced by traumatic brain injury is identical to that of disseminated intravascular coagulation with hyperfibrinolysis. Front Med. 2021;8:767637. doi:10.3389/fmed.2021.767637

8. Cannon JW, Dias JD, Kumar MA, et al. Use of thromboelastography in the evaluation and management of patients with traumatic brain injury: a systematic review and meta-analysis. Crit Care Explor. 2021;3(9):e0526. doi:10.1097/CCE.0000000000000526

9. Gan ZS, Stein SC, Swanson R, et al. Blood biomarkers for traumatic brain injury: a quantitative assessment of diagnostic and prognostic accuracy. Front Neurol. 2019;10:446. doi:10.3389/fneur.2019.00446

10. Gratz J, Güting H, Thorn S, et al. Protocolised thromboelastometric-guided haemostatic management in patients with traumatic brain injury: a pilot study. Anaesthesia. 2019;74(7):883-890. doi:10.1111/anae.14670

11. Nakae R, Murai Y, Wada T, et al. Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury. Sci Rep. 2022;12(1):19107. doi:10.1038/s41598-022-23912-4

12. Ebrahimi-Nejad F, Oraee-Yazdani S, Vahedi M, Peyravi Dehsorkhi M, Hosseini N, Hosseinzadeh S. Evaluating the efficacy of longitudinal coagulation biomarkers to predict in-hospital death in comatose TBI patients: a time-dependent roc curve approach. Med J Islam Repub Iran. 2025;39:63. doi:10.47176/mjiri.39.63

13. Niemeyer M, Jochems D, Houwert RM, van Es MA, Leenen L, van Wessem K. Mortality in polytrauma patients with moderate to severe TBI on par with isolated TBI patients: TBI as last frontier in polytrauma patients. Injury. 2022;53(4):1443-1448. doi:10.1016/j.injury.2022.01.009

14. Hubbard WB, Sim MMS, Saatman KE, Sullivan PG, Wood JP. Tissue factor release following traumatic brain injury drives thrombin generation. Res Pract Thromb Haemost. 2022;6(4):e12734. doi:10.1002/rth2.12734

15. Hijazi N, Abu Fanne R, Abramovitch R, et al. Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice. Blood. 2015;125(16):2558-2567. doi:10.1182/blood-2014-08-588442

16. Mavroudis I, Petridis F, Kazis D, et al. The diagnostic and prognostic role of biomarkers in mild traumatic brain injury: an umbrella meta-analysis. Brain Sci. 2025;15(6):581. doi:10.3390/brainsci15060581

17. Pryzmont M, Kosciuczuk U, Maciejczyk M. Biomarkers of traumatic brain injury: narrative review and future prospects in neurointensive care. Front Med. 2025;12:1539159. doi:10.3389/fmed.2025.1539159

18. Volod O, Bunch CM, Zackariya N, et al. Viscoelastic hemostatic assays: a primer on legacy and new generation devices. J Clin Med. 2022;11(3):860. doi:10.3390/jcm11030860

19. Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228-232. doi:10.1002/ajh.23599

20. Hiwase AD, Ovenden CD, Kaukas LM, et al. Can rotational thromboelastometry rapidly identify theragnostic targets in isolated traumatic brain injury? Emerg Med Australas. 2025;37(1):e14480. doi:10.1111/1742-6723.14480

21. Ivanov II, Apta BHR, Bonna AM, Harper MT. Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes. Sci Rep. 2019;9(1):13397. doi:10.1038/s41598-019-49635-7

22. Jin J, Wang F, Tian J, et al. Neutrophil extracellular traps contribute to coagulopathy after traumatic brain injury. JCI Insight. 2023;8(6):e141110. doi:10.1172/jci.insight.141110

23. Lapić I, Rogić D, Bingula M, Miklić L, Gornik I. Age-adjusted cut-off values for glial fibrillary acidic protein and ubiquitin carboxy-terminal hydrolase L1 improve the diagnostic accuracy of the Abbott mild traumatic brain injury assay. Diagnostics. 2025;15(9):1093. doi:10.3390/diagnostics15091093

24. Zarei H, Roshdi Dizaji S, Toloui A, Yousefifard M, Esmaeili A. Diagnostic and prognostic values of S100B versus neuron specific enolase for traumatic brain injury; a systematic review and meta-analysis. Arch Acad Emerg Med. 2024;12(1):e29. doi:10.22037/aaem.v12i1.2222

25. Huibregtse ME, Bazarian JJ, Shultz SR, Kawata K. The biological significance and clinical utility of emerging blood biomarkers for traumatic brain injury. Neurosci Biobehav Rev. 2021;130:433-447. doi:10.1016/j.neubiorev.2021.08.029

26. Mondello S, Amrein K, Czeiter E, 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):1256-1286. doi:10.1089/neu.2024.0620

27. Schmidt AE, Israel AK, Refaai MA. The utility of thromboelastography to guide blood product transfusion. Am J Clin Pathol. 2019;152(4):407-422. doi:10.1093/ajcp/aqz074

28. Pilar MR, Proctor EK, Pineda JA. Development, implementation, and evaluation of a novel guideline engine for pediatric patients with severe traumatic brain injury: a study protocol. Implement Sci Commun. 2020;1:31. doi:10.1186/s43058-020-00012-w

29. Oris C, Kahouadji S, Bouvier D, Sapin V. Blood biomarkers for the management of mild traumatic brain injury in clinical practice. Clin Chem. 2024;70(8):1023-1036. doi:10.1093/clinchem/hvae049

30. Ghaith HS, Nawar AA, Gabra MD, et al. A literature review of traumatic brain injury biomarkers. Mol Neurobiol. 2022;59(7):4141-4158. doi:10.1007/s12035-022-02822-6

31. Hou Y, Li H, Zhu L, et al. A review of natural compounds to regulate platelet aggregation: molecular mechanism and research advance. Front Pharmacol. 2025;16:1537776. doi:10.3389/fphar.2025.1537776

32. Alsaadi N, Younes R, Killinger JR, et al. Predictive value of platelet function assays in traumatic brain injury patients on antiplatelet therapy. J Trauma Acute Care Surg. 2025;98(4):550-556. doi:10.1097/TA.0000000000004557

33. Martin GE, Xia B, Kim Y, et al. Platelet function changes in a time-dependent manner following traumatic brain injury in a murine model. Shock. 2018;50(5):551-556. doi:10.1097/SHK.0000000000001056

34. Baksaas-Aasen K, Gall LS, Stensballe J, et al. Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial. Intensive Care Med. 2021;47(1):49-59. doi:10.1007/s00134-020-06266-1

35. Lieschke F, Marggrander DT, Kohlhase KD, et al. Coagulopathy, injury severity and bleeding progression but not prior antiplatelet and anticoagulation therapies drive prognosis in patients with moderate to severe traumatic brain injury. Front Neurol. 2025;16:1592583. doi:10.3389/fneur.2025.1592583

36. Walsh M, Moore EE, Moore HB, et al. Whole blood, fixed ratio, or goal-directed blood component therapy for the initial resuscitation of severely hemorrhaging trauma patients: a narrative review. J Clin Med. 2021;10(2):320. doi:10.3390/jcm10020320

37. Armstead WM, Vavilala MS. Improving understanding and outcomes of traumatic brain injury using bidirectional translational research. J Neurotrauma. 2020;37(22):2372-2380. doi:10.1089/neu.2018.6119