Coagulation disorders after traumatic brain injury
First Online: 02 January 2008 Received: 10 April 2007 Accepted: 01 October 2007 DOI:
Cite this article as: Harhangi, B., Kompanje, E., Leebeek, F. et al. Acta Neurochir (Wien) (2008) 150: 165. doi:10.1007/s00701-007-1475-8 Summary Background. Over the past decade new insights in our understanding of coagulation have identified the prominent role of tissue factor. The brain is rich in tissue factor, and injury to the brain may initiate disturbances in local and systemic coagulation. We aimed to review the current knowledge on the pathophysiology, incidence, nature, prognosis and treatment of coagulation disorders following traumatic brain injury (TBI). Methods. We performed a MEDLINE search from 1966 to April 2007 with various MESH headings, focusing on head trauma and coagulopathy. We identified 441 eligible English language studies. These were reviewed for relevance by two independent investigators. A meta-analysis was performed to calculate the frequencies of coagulopathy after TBI and to determine the association of coagulopathy and outcome, expressed as odds ratios. Results. Eighty-two studies were relevant for the purpose of this review. Meta-analysis of 34 studies reporting the frequencies of coagulopathy after TBI, showed an overall prevalence of 32.7%. The presence of coagulopathy after TBI was related both to mortality (OR 9.0; 95%CI: 7.3–11.6) and unfavourable outcome (OR 36.3; 95%CI: 18.7–70.5). Conclusions. We conclude that coagulopathy following traumatic brain injury is an important independent risk factor related to prognosis. Routine determination of the coagulation status should therefore be performed in all patients with traumatic brain injury. These data may have important implications in patient management. Well-performed prospective clinical trials should be undertaken as a priority to determine the beneficial effects of early treatment of coagulopathy. Keywords: DIC; coagulopathy; meta-analysis; prognosis; review; treatment; traumatic brain injury; head trauma.
Correspondence: B. Sanjay Harhangi, M.D., Ph.D., Department of Neurosurgery, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
References Aiyagari, V, Menendez, JA, Diringer, MN 2005 Apo E genotype not associated with intravascular coagulation in traumatic brain injury J Crit Care 20 176 179 PubMed Google Scholar Alvarez-Sabin, J, Turon, A, Lozano-Sanchez, M, Vazquez, J, Codina, A 1995 Delayed posttraumatic haemorrhage. “Spat-apoplexie” Stroke 26 1531 1535 PubMed Google Scholar Anonymous 1982 Disseminated intravascular coagulation and head injury Lancet 2 531 Google Scholar Anonymous 1989 Abnormal blood clotting after head injury Lancet 2 957 958 Google Scholar Anzil, AP 1974 Letter: defibrination after head trauma N Engl J Med 291 632 633 PubMed CrossRef Google Scholar Armand, R, Hess, JR 2003 Treating coagulopathy in trauma patients Transfus Med Rev 17 223 231 PubMed Google Scholar Astrup, T 1965 Assay and content of tissue thromboplastin in different organs Thromb Diath Haemorrh 14 401 416 PubMed Google Scholar Auer, L 1978 Disturbances of the coagulatory system in patients with severe cerebral trauma. I Acta Neurochir (Wien) 43 51 59 Google Scholar Auer, LM, Ott, E 1979 Disturbances of the coagulatory system in patients with severe cerebral trauma II. Platelet function Acta Neurochir (Wien) 49 219 226 Google Scholar Avikainen, V 1977 Coagulation disorders in severely and critically injured patients Ann Chir Gynaecol 66 269 277 PubMed Google Scholar Bachli, E 2000 History of tissue factor Br J Haematol 110 248 255 PubMed Google Scholar Bakhtiari, K, Meijers, JC, de Jonge, E, Levi, M 2004 Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation Crit Care Med 32 2416 2421 PubMed Google Scholar Bayir, A, Kalkan, E, Kocak, S, Ak, A, Cander, B, Bodur, S 2006 Fibrinolytic markers and neurologic outcome in traumatic brain injury Neurol India 54 363 365 PubMed Google Scholar
Becker S, Schneider W, Kreuz W, Jacobi G, Scharrer I, Nowak-Gottl U (1999) Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma. Eur J Pediatr (158 Suppl 3): S197–S202
Bennett, B, Ratnoff, OD 1972 The normal coagulation mechanism Med Clin North Am 56 95 104 PubMed Google Scholar Bernard, GR, Vincent, JL, Laterre, PF, LaRosa, SP, Dhainaut, JF, Lopez-Rodriguez, A, Steingrub, JS, Garber, GE, Helterbrand, JD, Ely, EW, Fisher, CJ, Jr 2001 Efficacy and safety of recombinant human activated protein C for severe sepsis N Engl J Med 344 699 709 PubMed Google Scholar Boffard, KD, Riou, B, Warren, B, Choong, PI, Rizoli, S, Rossaint, R, Axelsen, M, Kluger, Y 2005 Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials J Trauma 59 8 15 PubMed Google Scholar Bredbacka, S, Edner, G 1994 Soluble fibrin and D-dimer as detectors of hypercoagulability in patients with isolated brain trauma J Neurosurg Anesth 6 75 82 Google Scholar Brohi, K, Singh, J, Heron, M, Coats, T 2003 Acute traumatic coagulopathy J Trauma 54 1127 1130 PubMed Google Scholar Carrick, MM, Tyroch, AH, Youens, CA, Handley, T 2005 Subsequent development of thrombocytopenia and coagulopathy in moderate and severe head injury: support for serial laboratory examination J Trauma 58 725 729 PubMed CrossRef Google Scholar Chang, EF, Meeker, M, Holland, MC 2006 Acute traumatic intraparenchymal haemorrhage: risk factors for progression in the early post-injury period Neurosurgery 58 647 656 PubMed Google Scholar Chiaretti, A, Piastra, M, Pulitano, S, Pietrini, D, De Rosa, G, Barbaro, R, Di Rocco, C 2002 Prognostic factors and outcome of children with severe head injury: an 8-year experience Childs Nerv Syst 18 129 136 PubMed Google Scholar Clark, JA, Finelli, RE, Netsky, MG 1980 Disseminated intravascular coagulation following cranial trauma. Case report J Neurosurg 52 266 269 PubMed Google Scholar Cortiana, M, Zagara, G, Fava, S, Seveso, M 1986 Coagulation abnormalities in patients with head injury J Neurosurg Sci 30 133 138 PubMed Google Scholar Cube, HM 1976 Letter: intravascular coagulation following trauma J Neurosurg 44 400 PubMed Google Scholar Dalens, B, Bezou, MJ 1983 Coagulopathy following brain injury J Pediatr 102 166 PubMed Google Scholar de Jonge, E, Levi, M, Stoutenbeek, CP, van Deventer, SJ 1998 Current drug treatment strategies for disseminated intravascular coagulation Drugs 55 767 777 PubMed Google Scholar Drayer, BP, Poser, CM 1975 Disseminated intravascular coagulation and head trauma. Two case studies Jama 231 174 175 PubMed Google Scholar Dutton, RP, McCunn, M, Hyder, M, D’Angelo, M, O’Connor, J, Hess, JR, Scalea, TM 2004 Factor VIIa for correction of traumatic coagulopathy J Trauma 57 709 718 PubMed CrossRef Google Scholar Etemadrezaie, H, Baharvahdat, H, Shariati, Z, Lari, SM, Shakeri, MT, Ganjeifar, B 2007 The effect of fresh frozen plasma in severe closed head injury Clin Neurol Neurosurg 109 166 171 PubMed Google Scholar Fabbri, A, Vandelli, A, Servadei, F, Marchesini, G 2004 Coagulopathy and NICE recommendations for patients with mild head injury J Neurol Neurosurg Psychiatry 75 1787 1788 PubMed Google Scholar Fourrier, F 2004 Recombinant human activated protein C in the treatment of severe sepsis: an evidence-based review Crit Care Med 32 S534 S541 PubMed Google Scholar Gando, S 2001 Disseminated intravascular coagulation in trauma patients Semin Thromb Hemost 27 585 592 PubMed Google Scholar Gando, S, Tedo, I, Kubota, M 1992 Posttrauma coagulation and fibrinolysis Crit Care Med 20 594 600 PubMed Google Scholar Giesen, PL, Nemerson, Y 2000 Tissue factor on the loose Semin Thromb Hemost 26 379 384 PubMed Google Scholar Goldstein, B, Nadel, S, Peters, M, Barton, R, Machado, F, Levy, H, Haney, DJ, Utterback, B, Williams, MD, Giroir, BP 2006 ENHANCE: results of a global open-label trial of drotrecogin alfa (activated) in children with severe sepsis Pediatr Crit Care Med 7 200 211 PubMed Google Scholar Gomez, PA, Lobato, RD, Ortega, JM, De La Cruz, J 1996 Mild head injury: differences in prognosis among patients with a Glasgow Coma Scale score of 13 to 15 and analysis of factors associated with abnormal CT findings Br J Neurosurg 10 453 460 PubMed Google Scholar Goodnight, SH, Jr 1977 Defibrination following head injury Compr Ther 3 25 28 PubMed Google Scholar Goodnight, SH, Kenoyer, G, Rapaport, SI, Patch, MJ, Lee, JA, Kurze, T 1974 Defibrination after brain-tissue destruction: a serious complication of head injury N Engl J Med 290 1043 1047 PubMed CrossRef Google Scholar Grenander, A, Bredbacka, S, Rydvall, A, Aroch, R, Edner, G, Koskinen, LO, Olivecrona, M 2001 Antithrombin treatment in patients with traumatic brain injury: a pilot study J Neurosurg Anesth 13 49 56 Google Scholar Hoots, WK 1997 Experience with antithrombin concentrates in neurotrauma patients Semin Thromb Hemost 23 3 16 PubMed Google Scholar Hoyt, DB 2004 A clinical review of bleeding dilemmas in trauma Semin Hematol 41 40 43 PubMed Google Scholar Hulka, F, Mullins, RJ, Frank, EH 1996 Blunt brain injury activates the coagulation process Arch Surg 131 923 927 PubMed Google Scholar Hymel, KP, Abshire, TC, Luckey, DW, Jenny, C 1997 Coagulopathy in pediatric abusive head trauma Pediatrics 99 371 375 PubMed Google Scholar Kaufman, HH, Hui, KS, Mattson, JC, Borit, A, Childs, TL, Hoots, WK, Bernstein, DP, Makela, ME, Wagner, KA, Kahan, BD 1984 Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury Neurosurgery 15 34 42 PubMed Google Scholar Kaufman, HH, Moake, JL, Olson, JD, Miner, ME, duCret, RP, Pruessner, JL, Gildenberg, PL 1980 Delayed and recurrent intracranial haematomas related to disseminated intravascular clotting and fibrinolysis in head injury Neurosurgery 7 445 449 PubMed Google Scholar Kaufman, HH, Timberlake, G, Voelker, J, Pait, TG 1993 Medical complications of head injury Med Clin North Am 77 43 60 PubMed Google Scholar Kearney, TJ, Bentt, L, Grode, M, Lee, S, Hiatt, JR, Shabot, MM 1992 Coagulopathy and catecholamines in severe head injury J Trauma 32 608 611 PubMed Google Scholar Keimowitz, RM, Annis, BL 1973 Disseminated intravascular coagulation associated with massive brain injury J Neurosurg 39 178 180 PubMed Google Scholar Keller, MS, Fendya, DG, Weber, TR 2001 Glasgow Coma Scale predicts coagulopathy in pediatric trauma patients Semin Pediatr Surg 10 12 16 PubMed Google Scholar Kumura, E, Sato, M, Fukuda, A, Takemoto, Y, Tanaka, S, Kohama, A 1987 Coagulation disorders following acute head injury Acta Neurochir (Wien) 85 23 28 Google Scholar Kuo, JR, Chou, TJ, Chio, CC 2004 Coagulopathy as a parameter to predict the outcome in head injury patients – analysis of 61 cases J Clin Neurosci 11 710 714 PubMed Google Scholar Kushimoto, S, Shibata, Y, Yamamoto, Y 2003 Implications of fibrinogenolysis in patients with closed head injury J Neurotraum 20 357 363 Google Scholar Kushimoto, S, Yamamoto, Y, Shibata, Y, Sato, H, Koido, Y 2001 Implications of excessive fibrinolysis and alpha(2)-plasmin inhibitor deficiency in patients with severe head injury Neurosurgery 49 1084 1089 PubMed Google Scholar Lawson, JH, Kalafatis, M, Stram, S, Mann, KG 1994 A model for the tissue factor pathway to thrombin. I. An empirical study J Biol Chem 269 23357 23366 PubMed Google Scholar Levi, M 2005 Disseminated intravascular coagulation: what’s new? Crit Care Clin 21 449 467 PubMed Google Scholar Levi, M, Ten Cate, H 1999 Disseminated intravascular coagulation N Engl J Med 341 586 592 PubMed Google Scholar Mann, KG, Butenas, S, Brummel, K 2003 The dynamics of thrombin formation Arterioscler Thromb Vasc Biol 23 17 25 PubMed Google Scholar Martinowitz, U, Michaelson, M 2005 Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force J Thromb Haemost 3 640 648 PubMed Google Scholar May, AK, Young, JS, Butler, K, Bassam, D, Brady, W 1997 Coagulopathy in severe closed head injury: is empiric therapy warranted? Am Surg 63 233 236 PubMed Google Scholar Mayer, SA, Brun, NC, Begtrup, K, Broderick, J, Davis, S, Diringer, MN, Skolnick, BE, Steiner, T 2005 Recombinant activated factor VII for acute intracerebral haemorrhage N Engl J Med 352 777 785 PubMed Google Scholar McGauley, JL, Miller, CA, Penner, JA 1975 Diagnosis and treatment of diffuse intravascular coagulation following cerebral trauma. Case report J Neurosurg 43 374 376 PubMed Google Scholar Miner, ME, Kaufman, HH, Graham, SH, Haar, FH, Gildenberg, PL 1982 Disseminated intravascular coagulation fibrinolytic syndrome following head injury in children: frequency and prognostic implications J Pediatr 100 687 691 PubMed Google Scholar Morenski, JD, Tobias, JD, Jimenez, DF 2003 Recombinant activated factor VII for cerebral injury-induced coagulopathy in pediatric patients. Report of three cases and review of the literature J Neurosurg 98 611 616 PubMed CrossRef Google Scholar Muller-Berghaus, G, ten Cate, H, Levi, M 1999 Disseminated intravascular coagulation: clinical spectrum and established as well as new diagnostic approaches Thromb Haemost 82 706 712 PubMed Google Scholar Murray, GD, Butcher, I, McHugh, GS, Lu, J, Mushkudiani, NA, Maas, AI, Marmarou, A, Steyerberg, EW 2007 Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study J Neurotraum 24 329 337 Google Scholar Murshid, WR, Gader, AG 2002 The coagulopathy in acute head injury: comparison of cerebral versus peripheral measurements of haemostatic activation markers Br J Neurosurg 16 362 369 PubMed Google Scholar Nekludov, M, Antovic, J, Bredbacka, S, Blomback, M 2007 Coagulation abnormalities associated with severe isolated traumatic brain injury: cerebral arterio-venous differences in coagulation and inflammatory markers J Neurotraum 24 174 180 Google Scholar Olson, JD, Kaufman, HH, Moake, J, O’Gorman, TW, Hoots, K, Wagner, K, Brown, CK, Gildenberg, PL 1989 The incidence and significance of haemostatic abnormalities in patients with head injuries Neurosurgery 24 825 832 PubMed Google Scholar Ordog, GJ, Wasserberger, J, Balasubramanium, S 1985 Coagulation abnormalities in traumatic shock Ann Emerg Med 14 650 655 PubMed Google Scholar Owen, CA, Jr, Bowie, EJ 1979 Surgical haemostasis J Neurosurg 51 137 142 PubMed CrossRef Google Scholar Patel, NY, Hoyt, DB, Nakaji, P, Marshall, L, Holbrook, T, Coimbra, R, Winchell, RJ, Mikulaschek, AW 2000 Traumatic brain injury: patterns of failure of nonoperative management J Trauma 48 367 374 PubMed Google Scholar Pathak, A, Dutta, S, Marwaha, N, Singh, D, Varma, N, Mathuriya, SN 2005 Change in tissue thromboplastin content of brain following trauma Neurol India 53 178 182 PubMed Google Scholar Pattisapu, J, Miller, JD, Parent, AD 1985 Disseminated intravascular coagulation in patients with craniocerebral trauma J Miss State Med Assoc 26 347 350 PubMed Google Scholar Pfenninger, J, Plaschkes, J, Straume, BH 1982 Consumption coagulopathy after severe head injury in children Z Kinderchir 37 53 55 PubMed Google Scholar Piek, J, Chesnut, RM, Marshall, LF, van Berkum-Clark, M, Klauber, MR, Blunt, BA, Eisenberg, HM, Jane, JA, Marmarou, A, Foulkes, MA 1992 Extracranial complications of severe head injury J Neurosurg 77 901 907 PubMed CrossRef Google Scholar Pondaag, W 1979 Disseminated intravascular coagulation related to outcome in head injury Acta Neurochir Suppl (Wien) 28 98 102 Google Scholar Preston, FE, Malia, RG, Sworn, MJ, Timperley, WR, Blackburn, EK 1974 Disseminated intravascular coagulation as a consequence of cerebral damage J Neurol Neurosurg Psychiatry 37 241 248 PubMed Google Scholar Roberts, HR, Monroe, DM, Escobar, MA 2004 Current concepts of haemostasis: implications for therapy Anesthesiology 100 722 730 PubMed Google Scholar Roberts, I 2007 The CRASH-2 trial of an antifibrinolytic agent in traumatic haemorrhage: an international collaboration Indian J Med Res 125 5 7 PubMed Google Scholar Roseman, B 1985 Disseminated intravascular coagulation: a review Oral Surg Oral Med Oral Pathol 59 551 556 PubMed Google Scholar Rubin, RN, Colman, RW 1992 Disseminated intravascular coagulation. Approach to treatment Drugs 44 963 971 PubMed Google Scholar Sauaia, A, Moore, FA, Moore, EE, Moser, KS, Brennan, R, Read, RA, Pons, PT 1995 Epidemiology of trauma deaths: a reassessment J Trauma 38 185 193 PubMed Google Scholar Sawada, Y, Sadamitsu, D, Sakamoto, T, Ikemura, K, Yoshioka, T, Sugimoto, T 1984 Lack of correlation between delayed traumatic intracerebral haematoma and disseminated intravascular coagulation J Neurol Neurosurg Psychiatry 47 1125 1127 PubMed Google Scholar Scherer, RU, Spangenberg, P 1998 Procoagulant activity in patients with isolated severe head trauma Crit Care Med 26 149 156 PubMed Google Scholar Schreiber, MA, Differding, J, Thorborg, P, Mayberry, JC, Mullins, RJ 2005 Hypercoagulability is most prevalent early after injury and in female patients J Trauma 58 475 480 PubMed Google Scholar Selladurai, BM, Vickneswaran, M, Duraisamy, S, Atan, M 1997 Coagulopathy in acute head injury – a study of its role as a prognostic indicator Br J Neurosurg 11 398 404 PubMed Google Scholar Sherrington, RTA, Rhodes, A, Grounds, RM 2006 Intensive care and recombinant factor VIIa use: a review Neth J Crit Care 10 542 547 Google Scholar Sorensen, JV, Jensen, HP, Rahr, HB, Borris, LC, Lassen, MR, Fedders, O, Haase, JP, Knudsen, F 1993 Haemostatic activation in patients with head injury with and without simultaneous multiple trauma Scand J Clin Lab Inv 53 659 665 Google Scholar Stein, SC, Chen, XH, Sinson, GP, Smith, DH 2002 Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury J Neurosurg 97 1373 1377 PubMed Google Scholar Stein, SC, Smith, DH 2004 Coagulopathy in traumatic brain injury Neurocrit Care 1 479 488 PubMed Google Scholar Stein, SC, Spettell, C, Young, G, Ross, SE 1993 Delayed and progressive brain injury in closed-head trauma: radiological demonstration Neurosurgery 32 25 30 PubMed Google Scholar Stein, SC, Spettell, CM 1995 Delayed and progressive brain injury in children and adolescents with head trauma Pediatr Neurosurg 23 299 304 PubMed Google Scholar Stein, SC, Young, GS, Talucci, RC, Greenbaum, BH, Ross, SE 1992 Delayed brain injury after head trauma: significance of coagulopathy Neurosurgery 30 160 165 PubMed Google Scholar Strinchini, A, Baudo, F, Nosari, AM, Panzacchi, G, de Cataldo, F 1974 Letter: Defibrination and head injury Lancet 2 957 PubMed Google Scholar Takahasi, H, Urano, T, Nagai, N, Takada, Y, Takada, A 2000 Neutrophil elastase may play a key role in developing symptomatic disseminated intravascular coagulation and multiple organ failure in patients with head injury J Trauma 49 86 91 PubMed Google Scholar Tan, JE, Ng, I, Lim, J, Wong, HB, Yeo, TT 2004 Patients who talk and deteriorate: a new look at an old problem Ann Acad Med Singapore 33 489 493 PubMed Google Scholar Taylor, FB, Jr, Toh, CH, Hoots, WK, Wada, H, Levi, M 2001 Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation Thromb Haemost 86 1327 1330 PubMed Google Scholar Tikk, A, Noormaa, U 1979 The significance of cerebral and systemic disseminated intravascular coagulation in early prognosis of brain injury Acta Neurochir Suppl (Wien) 28 96 97 Google Scholar Tinnemans, JG, Gerritsen, SM 1980 Afibrinogenemia and blunt head injury Intens Care Med 6 211 213 Google Scholar Touho, H, Hirakawa, K, Hino, A, Karasawa, J, Ohno, Y 1986 Relationship between abnormalities of coagulation and fibrinolysis and postoperative intracranial haemorrhage in head injury Neurosurgery 19 523 531 PubMed Google Scholar Ueda, S, Fujitsu, K, Fujino, H, Sekino, T, Kuwabara, T 1985 Correlation between plasma fibrin-fibrinogen degradation product values and CT findings in head injury J Neurol Neurosurg Psychiatry 48 58 60 PubMed CrossRef Google Scholar Vaisrub, S 1973 Covert consumption coagulopathy – a call to vigilance Jama 224 1523 PubMed Google Scholar van der Sande, JJ, Emeis, JJ, Lindeman, J 1981 Intravascular coagulation: a common phenomenon in minor experimental head injury J Neurosurg 54 21 25 PubMed Google Scholar van der Sande, JJ, Veltkamp, JJ, Boekhout-Mussert, RJ, Bouwhuis-Hoogerwerf, ML 1978 Head injury and coagulation disorders J Neurosurg 49 357 365 PubMed Google Scholar Vavilala, MS, Dunbar, PJ, Rivara, FP, Lam, AM 2001 Coagulopathy predicts poor outcome following head injury in children less than 16 years of age J Neurosurg Anesth 13 13 18 Google Scholar Vecht, CJ, Minderhoud, JM, Sibinga, CT 1975 Platelet aggregability in relation to impaired consciousness after head injury J Clin Pathol 28 814 820 PubMed Google Scholar Vecht, CJ, Sibinga, CT 1974 Letter: head injury and defibrination Lancet 2 905 PubMed Google Scholar Vecht, CJ, Sibinga, CT, Minderhoud, JM 1975 Disseminated intravascular coagulation and head injury J Neurol Neurosurg Psychiatry 38 567 571 PubMed CrossRef Google Scholar Wasserberger, J, Bundage, B, Ordog, G, Scharfenberger, JA, Balasubramaniam, S 1984 DIC in head trauma Ann Emerg Med 13 987 988 PubMed Google Scholar Watts, C 1977 Disseminated intravascular coagulation Surg Neurol 8 258 262 PubMed Google Scholar White, CE, Schrank, AE, Baskin, TW, Holcomb, JB 2006 Effects of recombinant activated factor VII in traumatic nonsurgical intracranial haemorrhage Curr Surg 63 310 317 PubMed Google Scholar Winter, JP, Plummer, D, Bottini, A, Rockswold, GR, Ray, D 1989 Early fresh frozen plasma prophylaxis of abnormal coagulation parameters in the severely head-injured patient is not effective Ann Emerg Med 18 553 555 PubMed Google Scholar Wu, XH, Shi, XY, Gan, JX, Lu, XG, Jiang, GY, Zhou, JF 2003 Dynamically monitoring tissue factor and tissue factor pathway inhibitor following secondary brain injury Chin J Traumatol 6 114 117 PubMed Google Scholar Yadav, YR, Basoor, A, Jain, G, Nelson, A 2006 Expanding traumatic intracerebral contusion/haematoma Neurol India 54 377 381 PubMed CrossRef Google Scholar Yokota, H, Naoe, Y, Nakabayashi, M, Unemoto, K, Kushimoto, S, Kurokawa, A, Node, Y, Yamamoto, Y 2002 Cerebral endothelial injury in severe head injury: the significance of measurements of serum thrombomodulin and the von Willebrand factor J Neurotraum 19 1007 1015 Google Scholar Yusim, Y, Perel, A, Berkenstadt, H, Attia, M, Knoller, N, Sidi, A 2006 The use of recombinant factor VIIa (NovoSeven) for treatment of active or impending bleeding in brain injury: broadening the indications J Clin Anesth 18 545 551 PubMed Google Scholar