Нарушения системы гемостаза у пациентов в остром периоде изолированной черепно-мозговой травмы (обзор)

Острая изолированная черепно-мозговая травма (ЧМТ) часто связана с возникновением нарушений системы гемостаза, что может сопровождаться геморрагическими и ишемическими проявлениями в веществе головного мозга, в связи с чем нормальное функционирование свертывающей системы крови имеет критическое значение. Понимание патофизиологических механизмов данного явления может помочь адекватной профилактике вторичного повреждения головного мозга. Ранее, развитие синдрома диссеминированного внутрисосудистого свертывания (ДВС-синдрома) являлось общепринятой гипотезой механизма нарушений свертывающей системы при ЧМТ. Однако, за последние десятилетия появлялись новые данные о ключевой роли тканевого фактора, системного воспалительного ответа, тромбоцитопатии, эффекта протеина C в возникновении данной коагулопатии. Целью данного обзора литературы являлся предоставление новых данных о конкретных патофизиологических механизмах, лежащих в основе коагулопатии после ЧМТ.

1. Stein S.C., Chen X.H., Sinson G.P., Smith D.H. Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury. J. Neurosurg. 2002; 97 (6): 1373-1377. DOI: 10.3171/jns.2002.97.6.1373. PMID: 12507136

2. Stein S.C., Young G.S., Talucci R.C., Greenbaum B.H., Ross S.E. Delayed brain injury after head trauma: significance of coagulopathy. Neurosurgery. 1992; 30 (2): 160-165. DOI: 10.1097/00006123-199202000-00002. PMID: 1545882

3. Stein S.C., Spettell C., Young G., Ross S.E. Delayed and progressive brain injury in closed-head trauma: radiological demonstration. Neurosurgery. 1993; 32 (1): 25-30. DOI: 10.1097/00006123-199301000-00004. PMID: 8421553

4. 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. DOI: 10.1089/neu.2013.3241. PMID: 24738836

5. 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. DOI: 10.3171/jns.2002.96.1.0109. PMID: 11794591

6. 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. DOI: 10.1097/TA.0b013e3181ad5d37. PMID: 19901655

7. Потапов А.А., Лихтерман Л.Б., Кравчук А.Д., Охлопков В.А., Александрова Е.В., Филатова М.М., Маряхин А.Д., Латышев Я.А. Легкая черепно-мозговая травма. Клинические рекомендации. М.; 2016: 23.

8. Kaufman H.H., Hui K.S., Mattson J.C., Borit A., Childs T.L., Hoots W.K., Bernstein D.P., Makela M.E., Wagner K.A., Kahan B.D. Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury. Neurosurgery. 1984; 15 (1): 34-42. DOI: 10.1097/00006123-198407000-00007. PMID: 6472592

9. 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. DOI: 10.1227/01.NEU.0000108641.98845.88. PMID: 15028145

10. Schwarzmaier S.M., Kim S.W., Trabold R., Plesnila N. Temporal profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice. J. Neurotrauma. 2010; 27 (1): 121-130. DOI: 10.1089/neu.2009.1114. PMID: 19803784

11. Brohi K., Cohen M.J., Davenport R.A. Acute coagulopathy of trauma: mechanism, identification and effect. Curr. Opin. Crit. Care. 2007; 13 (6): 680685 DOI: 10.1097/MCC.0b013e3282f1e78f. PMID: 17975390

12. Cohen M.J., Brohi K., Ganter M.T., Manley G.T., Mackersie R.C., Pittet J.F. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J. Trauma. 2007; 63 (6): 1254-1261. DOI: 10.1097/TA.0b013e318156ee4c. PMID: 18212647

13. van der Sande J.J., Emeis J.J., Lindeman J. Intravascular coagulation: a common phenomenon in minor experimental head injury. J. Neurosurg. 1981; 54 (1): 21-25. DOI: 10.3171/jns.1981.54.1.0021. PMID: 7463116

14. Cortez S.C., McIntosh T.K., Noble L.J. Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res. 1989; 482 (2): 271-282. DOI: 10.1016/0006-8993(89)91190-6. PMID: 2706487

15. Dietrich W.D., Alonso O., Halley M. Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. J. Neurotrauma. 1994; 11 (3): 289-301. DOI: 10.1089/neu.1994.11.289. PMID: 7996583

16. Dietrich W.D., Alonso O., Busto R., Prado R., Dewanjee S., Dewanjee M.K., Ginsberg M.D. Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats. J. Cereb. Blood Flow Metab. 1996; 16 (3): 481489 DOI: 10.1097/00004647-199605000-00015. PMID: 8621753

17. Maeda T., Katayama Y., Kawamata T., Aoyama N., Mori T. Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor. Acta Neurochir. Suppl. 1997; 70: 102-105. DOI: 10.1007/978-3-7091-6837-0_32. PMID: 9416292

18. Scherer R.U., Spangenberg P. Procoagulant activity in patients with isolated severe head trauma. Crit. Care Med. 1998; 26 (1): 149-156. DOI: 10.1097/00003246-199801000-00031. PMID: 9428558

19. Hulka F., Mullins R.J., Frank E.H. Blunt brain injury activates the coagulation process. Arch. Surg. 1996; 131 (9): 923-927. DOI: 10.1001/archsurg.1996.01430210021004. PMID: 8790176

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

21. Pathak A., Dutta S., Marwaha N., Singh D., Varma N., Mathuriya S.N. Change in tissue thromboplastin content of brain following trauma. Neurol. India. 2005; 53 (2): 178-182. DOI: 10.4103/0028-3886.16404. PMID: 16010055

22. Halpern C.H., Reilly P.M., Turtz A.R., Stein S.C. Traumatic coagulopathy: the effect of brain injury. J. Neurotrauma. 2008; 25 (8): 997-1001. DOI: 10.1089/neu.2008.0548. PMID: 18687038

23. Nemerson Y., Giesen P.L. Some thoughts about localization and expression of tissue factor. Blood Coagul. Fibrinolysis. 1998; 9 (Suppl 1): S45S47. PMID: 9819028

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

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. DOI: 10.1089/neu.2007.0322. PMID: 18001200

26. 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. DOI: 10.1097/TA.0b013e3181d3cc58. PMID: 20386283

27. Laroche M., Kutcher M.E., Huang M.C., Cohen M.J., Manley G.T. Coagulopathy after traumatic brain injury. Neurosurgery. 2012; 70 (6): 13341345. DOI: 10.1227/NEU.0b013e31824d179b. PMID: 22307074

28. Maegele M. Coagulopathy after traumatic brain injury: incidence, pathogenesis, and treatment options. Transfusion. 2013; 53 (Suppl 1): 28S-37S. DOI: 10.1111/trf.12033. PMID: 23301970

29. Баранич А.И., Савин И.А., Табасаранский Т.Ф., Полупан А.А., Сычев А.А., Пилипенко Ю.В., Курдюмова Н.В., Микеладзе К.Г., Элиава Ш.Ш. Нарушения системы гемостаза у пациентов с аневризматическим субарахноидальным кровоизлиянием. Вопросы нейрохирургии им. Н.Н.Бурденко. 2018; 82 (4): 109-116. PMID: 30137045

30. Harhangi B.S., Kompanje E.J., Leebeek F.W., Maas A.I. Coagulation disorders after traumatic brain injury. Acta Neurochir. (Wien). 2008; 150 (2): 165-175. DOI: 10.1007/s00701-007-1475-8. PMID: 18166989

31. Keimowitz R.M., Annis B.L. Disseminated intravascular coagulation associated with massive brain injury. J. Neurosurg. 1973; 39 (2): 178-180. DOI: 10.3171/jns.1973.39.2.0178. PMID: 4719695

32. Goodnight S.H., Kenoyer G., Rapaport S.I., Patch M.J., Lee J.A., Kurze T. Defibrination after bain-tissue destruction: a serious complication of head injury. N. Engl. J. Med. 1974; 290 (19): 1043-1047. DOI: 10.1056/NEJM197405092901903. PMID: 4821906

33. Mackman N. Tissue-specific hemostasis: role of tissue factor. J. Thromb. Haemost. 2008; 6 (2): 303-305. DOI: 10.1111/j.1538-7836.2007.02873.x. PMID: 18088348

34. Gando S. Disseminated intravascular coagulation in trauma patients. Semin. Thromb. Hemost. 2001; 27 (6): 585–592. DOI: 10.1055/s-200118864. PMID: 11740682

35. Reilly P., Bullock R. Head injury, pathophysiology and management. 2nd ed. Hodder Arnold; 2005: 129-130. ISBN 0340-80724-5

36. Matta B., Menon D., Turner J. Textbook of neuroanaesthesia and critical care. Chapter: Management of acute head injury. London: Greenwich Medical Media Ltd; 2000: 285-297. ISBN 1-900151-73-1

37. van der Sande J.J., Veltkamp J.J., Boekhout-Mussert R.J., Bouwhuis-Hoogerwerf M.L. Head injury and coagulation disorders. J. Neurosurg. 1978; 49 (3): 357-365. DOI: 10.3171/jns.1978.49.3.0357. PMID: 681997

38. Olson J.D., Kaufman H.H., Moake J., O’Gorman T.W., Hoots K., Wagner K., Brown C.K., Gildenberg P.L. The incidence and significance of hemostatic abnormalities in patients with head injuries. Neurosurgery. 1989; 24 (6): 825-832. DOI: 10.1097/00006123-198906000-00007. PMID: 2747858

39. Takahashi H., Urano T., Takada Y., Nagai N., Takada A. Fibrinolytic parameters as an admission prognostic marker of head injury in patients who talk and deteriorate. J. Neurosurg. 1997; 86 (5): 768-772. DOI: 10.3171/jns.1997.86.5.0768. PMID: 9126890

40. Morel N., Morel O., Petit L., Hugel B., Cochard J.F., Freyssinet J.M., Sztark F., Dabadie P. Generation of procoagulant microparticles in cerebrospinal fluid and peripheral blood after traumatic brain injury. J. Trauma. 2008; 64 (3): 698-704. DOI: 10.1097/TA.0b013e31816493ad. PMID: 18332810

41. Morel N., Morel O., Delabranche X., Jesel L., Sztark F., Dabadie P., Freyssinet J.M., Toti F. Microparticles during sepsis and trauma. A link between inflammation and thrombotic processes. Ann. Fr. Anesth. Reanim. 2006; 25 (9): 955-966. DOI: 10.1016/j.annfar.2006.04.013. PMID: 16926090

42. Reininger A.J., Heijnen H.F., Schumann H., Specht H.M., Schramm W., Ruggeri Z.M. Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress. Blood. 2006; 107 (9): 3537-3545. DOI: 10.1182/blood-2005-02-0618. PMID: 16449527

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

44. Burnier L., Fontana P., Kwak B.R., Angelillo-Scherrer A. Cell-derived microparticles in haemostasis and vascular medicine. Thromb. Haemost. 2009; 101 (3): 439-451. DOI: 10.1160/TH08-08-0521. PMID: 19277403

45. 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. DOI: 10.1089/neu.2013.3168. PMID: 24956150

46. Vikerfors A., Mobarrez F., Bremme K., Holmström M., Ågren A., Eelde A., Bruzelius M., Antovic A., Wallén H., Svenungsson E. Studies of microparticles in patients with the antiphospholipid syndrome (APS). Lupus. 2012; 21 (7): 802-805. DOI: 10.1177/0961203312437809. PMID: 22635239

47. Lustenberger T., Talving P., Kobayashi L., Inaba K., Lam L., Plurad D., Demetriades D. Time course of coagulopathy in isolated severe traumatic brain injury. Injury. 2010; 41 (9): 924-928. DOI: 10.1016/j.injury.2010.04.019. PMID: 20471013

48. Cortiana M., Zagara G., Fava S., Seveso M. Coagulation abnormalities in patients with head injury. J. Neurosurg. Sci. 1986; 30 (3): 133-138. PMID: 3783267

49. Kutcher M.E., Redick B.J., McCreery R.C., Crane I.M., Greenberg M.D., Cachola L.M., Nelson M.F., Cohen M.J. Characterization of platelet dysfunction after trauma. J. Trauma Acute Care Surg. 2012; 73 (1): 13-19. DOI: 10.1097/TA.0b013e318256deab. PMID: 22743367

50. Vecht C.J., Minderhoud J.M., Sibinga C.T. Platelet aggregability in relation to impaired consciousness after head injury. J. Clin. Pathol. 1975; 28 (10): 814-820. DOI: 10.1136/jcp.28.10.814. PMID: 1214015

51. Saillant N.N., Sims C.A. Platelet dysfunction in injured patients. Mol. Cell Ther. 2014; 2: 37. DOI: 10.1186/s40591-014-0037-8. PMID: 26056601

52. Donahue D.L., Beck J., Fritz B., Davis P., Sandoval-Cooper M.J., Thomas S.G., Yount R.A., Walsh M., Ploplis V.A., Castellino F.J. Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans. J. Neurotrauma. 2014; 31 (4): 404-410. DOI: 10.1089/neu.2013.3089. PMID: 24040968

53. Lapetina E.G., Cuatrecasas P. Rapid inactivation of cyclooxygenase activity after stimulation of intact platelets. Proc. Natl. Acad. Sci. USA. 1979; 76 (1): 121-125. DOI: 10.1073/pnas.76.1.121. PMID: 218191

54. 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. DOI: 10.1016/j.jamcollsurg.2012.01.050. PMID: 22520693

55. 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. DOI: 10.1097/TA.0000000000000216. PMID: 24747445

56. 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 injuryinduced coagulopathy. Neurocrit. Care. 2012; 18 (2): 201–208. DOI: 10.1007/s12028-012-9745-6. PMID: 22847397

57. 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. DOI: 10.1016/j.jss.2014.08.016. PMID: 25218281

58. 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 defied by routine laboratory tests: which laboratory values matter? J. Trauma Acute Care Surg. 2014; 76 (1): 121–125. DOI: 10.1097/TA.0b013e3182a9cc95. PMID: 24368366

59. Massaro A.M., Doerfler S., Nawalinski K., Michel B., Driscoll N., Ju C., Patel H., Quattrone F., Frangos S., Maloney-Wilensky E., Sean Grady M., Stein S.C., Kasner S.E., Kumar M.A. Thromboelastography defies late hypercoagulopathy after TBI: a pilot study. Neurocrit. Care. 2015; 22 (1): 45–51. DOI: 10.1007/s12028-014-0051-3. PMID: 25127903

60. Corps K.N., Roth T.L., McGavern D.B. Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 2015; 72 (3): 355-362. DOI: 10.1001/jamaneurol.2014.3558. PMID: 25599342

61. Ramlackhansingh A.F., Brooks D.J., Greenwood R.J., Bose S.K., Turkheimer F.E., Kinnunen K.M., Gentleman S., Heckemann R.A., Gunanayagam K., Gelosa G., Sharp D.J. Inflammation after trauma: microglial activation and traumatic brain injury. Ann. Neurol. 2011; 70 (3): 374-383. DOI: 10.1002/ana.22455. PMID: 21710619

62. Ярилин А.А. Иммунология. М.: ГЭОТАР-Медиа; 2010: 93-96. ISBN 978-5-9704-1319-7

63. Russo M.V., McGavern D.B. Immune surveillance of the CNS following infection and injury. Trends Immunol. 2015; 36 (10): 637-650. DOI: 10.1016/j.it.2015.08.002. PMID: 26431941

64. Bianchi M.E. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 2007; 81 (1): 1-5. DOI: 10.1189/jlb.0306164. PMID: 17032697

65. Morgan B.P. Mechanisms of tissue damage by the membrane attack complex of complement. Complement Inflamm. 1989; 6 (2): 104-111. DOI: 10.1159/000463082. PMID: 2656078

66. Martel C., Cointe S., Maurice P., Matar S., Ghitescu M., Théroux P., Bonnefoy A. Requirements for membrane attack complex formation and anaphylatoxins binding to collagen-activated platelets. PLoS One. 2011; 6 (4): e18812. DOI: 10.1371/journal.pone.0018812. PMID: 21526204

67. Morgan B.P. The membrane attack complex as an inflammatory trigger. Immunobiology. 2016; 221 (6): 747-751. DOI: 10.1016/j.imbio.2015.04.006. PMID: 25956457

68. Bellander B.M., von Holst H., Fredman P., Svensson M. Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. J. Neurosurg. 1996; 85 (3): 468-475. DOI: 10.3171/jns.1996.85.3.0468. PMID: 8751634

69. Bellander B.M., Singhrao S.K., Ohlsson M., Mattsson P., Svensson M. Complement activation in the human brain after traumatic head injury. J. Neurotrauma. 2001; 18 (12): 1295-1311. DOI: 10.1089/08977150152725605. PMID: 11780861

70. Stahel P.F., Morganti-Kossmann M.C., Kossmann T. The role of the complement system in traumatic brain injury. Brain Res. Brain Res. Rev. 1998; 27 (3): 243-256. DOI: 10.1016/S0165-0173(98)00015-0. PMID: 9729408

71. Rostami E., Davidsson J., Gyorgy A., Agoston D.V., Risling M., Bellander B.M. The terminal pathway of the complement system is activated in focal penetrating but not in mild diffuse traumatic brain injury. J. Neurotrauma. 2013; 30 (23): 1954-1965. DOI: 10.1089/neu.2012.2583. PMID: 23808389

72. Bellander B.M., Olafsson I.H., Ghatan P.H., Bro Skejo H.P., Hansson L.O., Wanecek M., Svensson M.A. Secondary insults following traumatic brain injury enhance complement activation in the human brain and release of the tissue damage marker S100B. Acta Neurochir. (Wien). 2011; 153 (1): 90-100. DOI: 10.1007/s00701-010-0737-z. PMID: 20686797

73. Christiaans S.C., Wagener B.M., Esmon C.T., Pittet J.F. Protein C and acute inflammation: a clinical and biological perspective. Am. J. Physiol. Lung Cell Mol. Physiol. 2013; 305 (7): L455-L466. DOI: 10.1152/ajplung.00093.2013. PMID: 23911436

74. Kushimoto S., Shibata Y., Yamamoto Y. Implications of fibrinogenolysis in patients with closed head injury. J. Neurotrauma. 2003; 20 (4): 357363. DOI: 10.1089/089771503765172318. PMID: 12866815

75. Tian H.L., Chen H., Wu B.S., Cao H.L., Xu T., Hu J., Wang G., Gao W.W., Lin Z.K., Chen S.W. D-Dimer as a predictor of progressive hemorrhagic injury in patients with traumatic brain injury: analysis of 194 cases. Neurosurg. Rev. 2010; 33 (3): 359-365. DOI: 10.1007/s10143-010-0251-z. PMID: 20349100

76. 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. DOI: 10.1097/00006123-200111000-00011. PMID: 11846901

77. Auer L. Disturbances of the coagulatory system in patients with severe cerebral trauma. I. Acta Neurochir. (Wien). 1978; 43 (1-2): 51-59. DOI: 10.1007/BF01809225. PMID: 707171

78. Auer L.M., Ott E. Disturbances of the coagulatory system in patients with severe cerebral trauma II. Platelet function. Acta Neurochir. (Wien). 1979; 49 (3-4): 219-226. DOI: 10.1007/BF01808961. PMID: 517179

79. Touho H., Hirakawa K., Hino A., Karasawa J., Ohno Y. Relationship between abnormalities of coagulation and fibrinolysis and postoperative intracranial hemorrhage in head injury. Neurosurgery. 1986; 19 (4): 523-531. DOI: 10.1227/00006123-198610000-00005. PMID: 3785592

80. Crone K.R., Lee K.S., Kelly D.L.Jr. Correlation of admission fibrin degradation products with outcome and respiratory failure in patients with severe head injury. Neurosurgery. 1987; 21 (4): 532-536. DOI: 10.1227/00006123-198710000-00015. PMID: 3683787

81. Selladurai B.M., Vickneswaran M., Duraisamy S., Atan M. Coagulopathy in acute head injury: a study of its role as a prognostic indicator. Br. J. Neurosurg. 1997; 11 (5): 398-404. DOI: 10.1080/02688699745880. PMID: 9474270