Coagulopathy in the Acute Phase of Traumatic Brain Injury

Acute traumatic brain injury (TBI) can be accompanied by coagulopathy. In TBI, when an increased risk of hemorrhagic lesions in the brain tissue exists, keeping the normal hemostasis is crucial.

The aim: to determine the incidence of coagulopathy in the acute phase of isolated TBI and identify the correlation between the types of hemostasis disorders and the severity of TBI.

Materials and methods. We analyzed 323 case records of patients with TBI hospitalized to the Neurosurgery Center ICU from 2008 to 2016, 118 of them were included in the study. Criteria for inclusion were acute isolated TBI, hospitalization in the first 72 hours after injury, young and middle-aged patients. On admission to the hospital, all patients were assessed according to the Glasgow Coma Scale (GCS) and divided into two groups: group I with severe TBI, group 2 with mild and moderate TBI. All patients underwent blood coagulation testing (APTT, PTI, fibrinogen concentration, platelet count).

Results. In 63.6% of patients with acute TBI coagulopathy were found, most of them (55.1%) had hypocoagulability state and were observed in the group of severe PMT (62.5%). The most frequent signs of coagulopathy were reduced PTI of less than 70% and thrombocytopenia of less than 150×10⁹/l. A weak correlation (R=0.276; P=0.002) was found between the development of thrombocytopenia and adverse outcomes (1–3 points according to GOS).

Conclusion. on hospital admission coagulopathy was diagnosed in 63,6% of patients in the acute phase of TBI, hypocoagulability state prevailed. Coagulopathy was significantly more common in patients in the acute phase of severe TBI (GCS8 points).

The mechanisms of TBI-associated coagulopathy have not yet been fully clarified. Further studies of the role of platelet, plasma and fibrinolytic components in the development of coagulopathy are warranted, which require more comprehensive methods of hemostasis investigation.

1. Boto G.R., Gоmez P.A., De La Cruz J., Lobato R.D. Severe head injury and the risk of early death. J Neurol Neurosurg Psychiatry. 2006; 77 (9): 1054–1059. PMID: 16740580. PMCID: PMC2077742. DOI: 10.1136/jnnp.2005.087056

2. Juratli T.A., Zang B., Litz R.J., Sitoci K.H., Aschenbrenner U., Gottschlich B., Daubner D., Schackert G., Sobottka S.B. Early hemorrhagic progression of traumatic brain contusions: frequency, correlation with coagulation disorders, and patient outcome: a prospective study. J Neurotrauma. 2014; 31 (17): 1521–1527. PMID: 24738836. DOI: 10.1089/neu.2013.3241

3. Oertel M., Kelly D.F., McArthur D., Boscardin W.J., Glenn T.C., Lee J.H., Gravori T., Obukhov D., McBride D.Q., Martin N.A. Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J Neurosurg. 2002; 96 (1): 109–116. PMID: 11794591. DOI: 10.3171/jns.2002.96.1.0109

4. Baranich A.I., Sychev A.A., Savin I.А., Polupan A.A., Oshorov A.V., Potapov A.A. Hemostasis Disturbances in Patients in the Acute Period of Isolated Traumatic Brain Injury (Review). Obshchaya Reanimatologiya=General Reanimatology. 2018; 14 (5): 85–95. [In Russ.]. DOI: 10.15360/1813-9779-2018-5-85-95

5. Stein S.C., Smith D.H. Coagulopathy in traumatic brain injury. Neurocrit Care. 2004; 1 (4): 479–488. PMID: 16174954. DOI: 10.1385/NCC:1:4:479

6. Epstein D.S., Mitra B., O’Reilly G., Rosenfeld J.V., Cameron P.A. Acute traumatic coagulopathy in the setting of isolated traumatic brain injury: a systematic review and meta-analysis. Injury. 2014: 45 (5): 819–824. DOI: 10.1016/j.injury.2014.01.011

7. Talving P., Benfield R., Hadjizacharia P., Inaba K., Chan L.S., Demetriades D. Coagulopathy in severe traumatic brain injury: a prospective study. J Trauma. 2009; 66 (1): 55-61; discussion 61-2. PMID: 19131806. DOI: 10.1097/TA.0b013e318190c3c0

8. Allard C.B., Scarpelini S., Rhind S.G., Baker A.J., Shek P.N., Tien H., Fernando M., Tremblay L., Morrison L.J., Pinto R., Rizoli S.B. Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J Trauma. 2009; 67 (5): 959–967. PMID: 19901655. DOI: 10.1097/TA.0b013e3181ad5d37

9. Maegele M., Lefering R., Yucel N., Tjardes T., Rixen D., Paffrath T., Simanski C., Neugebauer E, Bouillon B. AG Polytrauma of the German Trauma Society (DGU). Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007; 38 (3): 298–304. PMID: 17214989. DOI: 10.1016/j.injury.2006.10.003

10. Stein S.C., Graham D.I., Chen X.H., Smith D.H. Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injury. Neurosurgery. 2004; 54 (3): 687–691; discussion 691. PMID: 15028145. DOI: 10.1227/01.neu.0000108641.98845.88

11. Zehtabchi S., Soghoian S., Liu Y., Carmody K., Shah L., Whittaker B., Sinert R. The association of coagulopathy and traumatic brain injury in patients with isolated head injury. Resuscitation. 2008; 76 (1): 52–56. PMID: 17706857. DOI: 10.1016/j.resuscitation.2007.06.024

12. Carrick M.M., Tyroch A.H., Youens C.A., Handley T. Subsequent development of thrombocytopenia and coagulopathy in moderate and severe head injury: support for serial laboratory examination. J Trauma. 2005; 58 (4): 725–729; discussion 729–730. PMID: 15824648. DOI: 10.1097/01.ta.0000159249.68363.78

13. Ranucci M., Simioni P. Point-of-Care Tests for Severe Hemorrhage. A Manual for Diagnosis and Treatment. Springer International Publishing. 2016: 12–23, 160–163.

14. Nakashima M.O., Rogers H.J. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res. 2014; 49 (2): 85–94. PMID: 25025009. PMCID: PMC4090343. DOI: 10.5045/br.2014.49.2.85

15. Caspers M., Schäfer N., Fröhlich M., Bauerfeind U., Bouillon B., Mutschler M., Maegele M. How do external factors contribute to the hypocoagulative state in trauma-induced coagulopathy? — In vitro analysis of the lethal triad in trauma. Scand J Trauma Resusc Emerg Med. 2018; 26 (1): 66: 2018. PMID: 30111342. PMCID: PMC6094881. DOI: 10.1186/s13049-018-0536-8

16. Agren A., Wikman A.T., Holmstrom M., Ostlund A., Edgren G. Thromboelastography (TEG) compared to conventional coagulation tests in surgical patients—a laboratory evaluation. Scand J Clin Lab Invest. 2013; 73 (3): 214–220. PMID: 23402666. DOI: 10.3109/00365513.2013.765960

17. Herbert J.P., Guillotte A.R., Hammer R.D., Litofsky N.S. Coagulopathy in the Setting of Mild Traumatic Brain Injury: Truths and Consequences. Brain Sci; 2017: 7 (7). PMID: 28737691. PMCID: PMC5532605. DOI: 10.3390/brainsci7070092

18. Nekludov M., Mobarrez F., Gryth D., Bellander B.M., Wallen H. Formation of microparticles in the injured brain of patients with severe isolated traumatic brain injury. J Neurotrauma. 2014; 31 (23): 1927–1933. PMID: 24956150. DOI: 10.1089/neu.2013.3168

19. Mooberry, M.J., Key N.S. Microparticle analysis in disorders of hemostasis and thrombosis. Cytometry A. 2016; 89 (2): 111–122. PMID: 25704723. PMCID: PMC4545474. DOI: 10.1002/cyto.a.22647

20. Kushimoto S., Yamamoto Y., Shibata Y., Sato H., Koido Y. Implications of excessive fibrinolysis and alpha (2)-plasmin inhibitor deficiency in patients with severe head injury. Neurosurgery. 2001; 49 (5): 1084–1089; discussion 1089–1090. PMID: 11846901. DOI: 10.1097/00006123200111000-00011

21. Laroche M., Kutcher M.E., Huang M.C., Cohen M.J., Manley G.T. Coagulopathy after traumatic brain injury. Neurosurgery. 2012; 70 (6): 1334–1345. PMID: 22307074. DOI: 10.1227/NEU.0b013e31824d179b

22. Wafaisade A., Lefering R., Tjardes T., Wutzler S., Simanski C., Paffrath T., Fischer P., Bouillon B., Maegele M; Trauma Registry of DGU. Acute coagulopathy in isolated blunt traumatic brain injury. Neurocrit Care. 2010; 12 (2): 211–219. PMID: 19806475. DOI: 10.1007/s12028-009-9281-1

23. Wohlauer M.V., Moore E.E., Thomas S., Sauaia A., Evans E., Harr J., Silliman C.C., Ploplis V., Castellino F.J., Walsh M. Early platelet dysfunction: an unrecognized role in the acute coagulopathy of trauma. J Am Coll Surg. 2012; 214 (5): 739–746. PMID: 22520693. PMCID: PMC3348700. DOI: 10.1016/j.jamcollsurg.2012.01.050

24. Castellino F.J., Chapman M.P., Donahue D.L., Thomas S, Moore E.E., Wohlauer M.V., Fritz B., Yount R., Ploplis V., Davis P., Evans E., Walsh M. Traumatic brain injury causes platelet adenosine diphosphate and arachidonic acid receptor inhibition independent of hemorrhagic shock in humans and rats. J Trauma Acute Care Surg. 2014; 76 (5): 1169–1176. PMID: 24747445. PMCID: PMC4065716. DOI: 10.1097/TA.0000000000000216

25. Nekludov M., Bellander B.M., Blombäck M., Wallen H.N. Platelet dysfunction in patients with severe traumatic brain injury. J Neurotrauma. 2007; 24 (11): 1699–1706. PMID: 18001200. DOI: 10.1089/neu.2007.0322

26. Briggs A., Gates J.D., Kaufman R.M., Calahan C., Gormley W.B., Havens J.M. Platelet dysfunction and platelet transfusion in traumatic brain injury. J Surg Res. 2015; 193 (2): 802–806. PMID: 25218281. DOI: 10.1016/j.jss.2014.08.016

27. Davis P.K., Musunuru H., Walsh M., Cassady R., Yount R., Losiniecki A., Moore E.E., Wohlauer M.V., Howard J., Ploplis V.A., Castellino F.J., Thomas S.G. Platelet dysfunction is an early marker for traumatic brain injury-induced coagulopathy. Neurocrit Care. 2013; 18 (2): p. 201–208. DOI: 10.1007/s12028-012-9745-6

28. Joseph B., Aziz H., Zangbar B., Kulvatunyou N., Pandit V., O’Keeffe T., Tang A., Wynne J., Friese R.S., Rhee P. Acquired coagulopathy of traumatic brain injury defined by routine laboratory tests: which laboratory values matter? J Trauma Acute Care Surg. 2014; 76 (1): 121–125. PMID: 24368366. DOI: 10.1097/TA.0b013e3182a9cc95

29. Schnüriger B., Inaba K., Abdelsayed G.A., Lustenberger T., Eberle B.M., Barmparas G., Talving P., Demetriades D. The impact of platelets on the progression of traumatic intracranial hemorrhage. J Trauma. 2010; 68 (4): 881–885. PMID: 20386283. DOI: 10.1097/TA.0b013e3181d3cc58

30. Sun Y., Wang J., Wu X., Xi C., Gai Y., Liu H, Yuan Q., Wang E., Gao L., Hu J., Zhou L. Validating the incidence of coagulopathy and disseminated intravascular coagulation in patients with traumatic brain injury-analysis of 242 cases. Br J Neurosurg. 2011; 25 (3): 363–368. DOI: 10.3109/02688697.2011.552650

31. Murray G.D., Butcher I., McHugh G.S., Lu J., Mushkudiani N.A., Maas A.I., Marmarou A., Steyerberg E.W. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007; 24 (2): 329–337. DOI: 10.1089/neu.2006.0035