{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:55:47Z","timestamp":1792205747043,"version":"4.4.0"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurocrit Care"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Almost two-thirds of patients with severe traumatic brain injury (TBI) develop some form of hemostatic disturbance, which contributes to poor outcome. While the initial head injury often leads to impaired clot formation, TBI is also associated with an increased risk of thrombosis. Most likely there is a progression from early bleeding to a later prothrombotic state. In this paper, we systematically review the literature on the time course of hemostatic disruptions following TBI. A MEDLINE search was performed for TBI studies reporting the trajectory of hemostatic assays over time. The search yielded 5,049 articles, of which 4,910 were excluded following duplicate removal as well as title and abstract review. Full-text assessment of the remaining articles yielded 33 studies that were included in the final review. We found that the first hours after TBI are characterized by coagulation cascade dysfunction and hyperfibrinolysis, both of which likely contribute to lesion progression. This is then followed by platelet dysfunction and decreased platelet count, the clinical implication of which remains unclear. Later, a poorly defined prothrombotic state emerges, partly due to fibrinolysis shutdown and hyperactive platelets. In the clinical setting, early administration of the antifibrinolytic agent tranexamic acid has proved effective in reducing head-injury-related mortality in a subgroup of TBI patients. Further studies evaluating the time course of hemostatic disruptions after TBI are warranted in order to identify windows of opportunity for potential treatment options.<\/jats:p>","DOI":"10.1007\/s12028-020-01037-8","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T17:04:03Z","timestamp":1593536643000},"page":"635-656","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Time Course of Hemostatic Disruptions After Traumatic Brain Injury: A Systematic Review of the Literature"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-3045","authenticated-orcid":false,"given":"Alexander","family":"Fletcher-Sandersj\u00f6\u00f6","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Peter","family":"Thelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Maegele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Michael","family":"Bellander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"1037_CR1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13054-016-1318-1","volume":"20","author":"N Stocchetti","year":"2016","unstructured":"Stocchetti N, Zanier ER. Chronic impact of traumatic brain injury on outcome and quality of life: a narrative review. Crit Care. 2016;20:1\u201310.","journal-title":"Crit Care"},{"key":"1037_CR2","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S1474-4422(17)30197-7","volume":"16","author":"M Maegele","year":"2017","unstructured":"Maegele M, Sch\u00f6chl H, Menovsky T, Mar\u00e9chal H, Marklund N, Buki A, et al. Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management. Lancet Neurol. 2017;16:630\u201377.","journal-title":"Lancet Neurol"},{"key":"1037_CR3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00701-007-1475-8","volume":"150","author":"BS Harhangi","year":"2008","unstructured":"Harhangi BS, Kompanje EJO, Leebeek FWG, Maas AIR. Coagulation disorders after traumatic brain injury. Acta Neurochir (Wien). 2008;150:165\u201375.","journal-title":"Acta Neurochir (Wien)"},{"key":"1037_CR4","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1182\/blood-2016-01-636423","volume":"128","author":"R Chang","year":"2016","unstructured":"Chang R, Cardenas JC, Wade CE, Holcomb JB. Advances in the understanding of trauma-induced coagulopathy. Blood. 2016;128:1043\u20139.","journal-title":"Blood"},{"key":"1037_CR5","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3390\/brainsci7070092","volume":"7","author":"JP Herbert","year":"2017","unstructured":"Herbert JP, Guillotte AR, Hammer RD, Scott LN. Coagulopathy in the setting of mild traumatic brain injury: Truths and consequences. Brain Sci. 2017;7:92.","journal-title":"Brain Sci"},{"key":"1037_CR6","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.3390\/ijms21051596","volume":"21","author":"A Fletcher-Sandersj\u00f6\u00f6","year":"2020","unstructured":"Fletcher-Sandersj\u00f6\u00f6 A, Maegele M, Bellander B-M. Does complement-mediated hemostatic disturbance occur in traumatic brain injury? A literature review and observational study protocol. Int J Mol Sci. 2020;21:1596.","journal-title":"Int J Mol Sci"},{"key":"1037_CR7","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.surg.2015.02.029","volume":"158","author":"LE Folkerson","year":"2015","unstructured":"Folkerson LE, Sloan D, Cotton BA, Holcomb JB, Tomasek JS, Wade CE. Predicting progressive hemorrhagic injury from isolated traumatic brain injury and coagulation. Surgery. 2015;158:655\u201361.","journal-title":"Surgery"},{"key":"1037_CR8","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1182\/blood-2017-11-784108","volume":"131","author":"J Zhang","year":"2018","unstructured":"Zhang J, Zhang F, Dong JF. Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury. Blood. 2018;131:2001\u20136.","journal-title":"Blood."},{"key":"1037_CR9","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1089\/neu.2015.4205","volume":"33","author":"Q Yuan","year":"2016","unstructured":"Yuan Q, Sun YR, Wu XHX, Yu J, Li ZQ, Du ZY, et al. Coagulopathy in traumatic brain injury and its correlation with progressive hemorrhagic injury: a systematic review and meta-analysis. J Neurotrauma. 2016;33:1279\u201391.","journal-title":"J Neurotrauma"},{"key":"1037_CR10","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00134-016-4655-2","volume":"43","author":"MB Skrifvars","year":"2017","unstructured":"Skrifvars MB, Bailey M, Presneill J, French C, Nichol A, Little L, et al. Venous thromboembolic events in critically ill traumatic brain injury patients. Intensive Care Med. 2017;43:419\u201328.","journal-title":"Intensive Care Med"},{"key":"1037_CR11","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jcrc.2017.08.012","volume":"43","author":"BP Strollo","year":"2018","unstructured":"Strollo BP, Bennett GJ, Chopko MS, Guo WA. Timing of venous thromboembolism chemoprophylaxis after traumatic brain injury. J Crit Care. 2018;43:75\u201380.","journal-title":"J Crit Care"},{"key":"1037_CR12","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jss.2018.10.021","volume":"235","author":"NE Glass","year":"2019","unstructured":"Glass NE, Vadlamani A, Hwang F, Sifri ZC, Kunac A, Bonne S, et al. Bleeding and thromboembolism after TBI in the elderly: a real conundrum. J Surg Res. 2019;235:615\u201320.","journal-title":"J Surg Res"},{"key":"1037_CR13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.clineuro.2018.09.032","volume":"175","author":"LD Hachem","year":"2018","unstructured":"Hachem LD, Mansouri A, Scales DC, Geerts W, Pirouzmand F. Anticoagulant prophylaxis against venous thromboembolism following severe traumatic brain injury: a prospective observational study and systematic review of the literature. Clin Neurol Neurosurg. 2018;175:68\u201373.","journal-title":"Clin Neurol Neurosurg"},{"key":"1037_CR14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1097\/HTR.0000000000000035","volume":"30","author":"JS Albrecht","year":"2015","unstructured":"Albrecht JS, Liu X, Smith GS, Baumgarten M, Rattinger GB, Gambert SR, et al. Stroke incidence following traumatic brain injury in older adults HHS public access. J Head Trauma Rehabil. 2015;30:62\u20137.","journal-title":"J Head Trauma Rehabil"},{"key":"1037_CR15","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1161\/STROKEAHA.117.017327","volume":"48","author":"RG Kowalski","year":"2017","unstructured":"Kowalski RG, Haarbauer-Krupa JK, Bell JM, Corrigan JD, Hammond FM, Torbey MT, et al. Acute ischemic stroke after moderate to severe traumatic brain injury: incidence and impact on outcome. Stroke. 2017;48:1802\u20139.","journal-title":"Stroke"},{"key":"1037_CR16","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3390\/ijerph14030230","volume":"14","author":"SW Liu","year":"2017","unstructured":"Liu SW, Huang LC, Chung WF, Chang HK, Wu JC, Chen LF, et al. Increased risk of stroke in patients of concussion: A nationwide cohort study. Int J Environ Res Public Health. 2017;14:230.","journal-title":"Int J Environ Res Public Health"},{"key":"1037_CR17","doi-asserted-by":"crossref","first-page":"e740","DOI":"10.1016\/j.wneu.2018.10.130","volume":"122","author":"TT Eric Nyam","year":"2019","unstructured":"Eric Nyam TT, Ho CH, Chio CC, Lim SW, Wang JJ, Chang CH, et al. Traumatic brain injury increases the risk of major adverse cardiovascular and cerebrovascular events: a 13-year, population-based study. World Neurosurg. 2019;122:e740\u2013e53.","journal-title":"World Neurosurg"},{"key":"1037_CR18","doi-asserted-by":"crossref","unstructured":"McFarlane TD, Love J, Hanley S, Dixon BE, Hammond FM. Increased risk of stroke among young adults with serious traumatic brain injury. J Head Trauma Rehabil. 2019;1.","DOI":"10.1097\/HTR.0000000000000539"},{"key":"1037_CR19","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1089\/neu.2015.4039","volume":"33","author":"R Nakae","year":"2016","unstructured":"Nakae R, Takayama Y, Kuwamoto K, Naoe Y, Sato H, Yokota H. Time course of coagulation and fibrinolytic parameters in patients with traumatic brain injury. J Neurotrauma. 2016;33:688\u201395.","journal-title":"J Neurotrauma"},{"key":"1037_CR20","doi-asserted-by":"crossref","unstructured":"Nakae R, Yokobori S, Takayama Y, Kuwamoto K, Naoe Y, Yokota H. Age-related differences in fibrinolytic parameters in patients with acute traumatic brain injury. Surg Neurol Int 2017;8.","DOI":"10.4103\/sni.sni_56_17"},{"key":"1037_CR21","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.injury.2010.04.019","volume":"41","author":"T Lustenberger","year":"2010","unstructured":"Lustenberger T, Talving P, Kobayashi L, Inaba K, Lam L, Plurad D, et al. Time course of coagulopathy in isolated severe traumatic brain injury. Injury. 2010;41:924\u20138.","journal-title":"Injury"},{"key":"1037_CR22","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1089\/neu.2007.0322","volume":"24","author":"M Nekludov","year":"2007","unstructured":"Nekludov M, Bellander B-MM, Blomb\u00e4ck M, Wallen HN, Blomback M, Wallen HN. Platelet dysfunction in patients with severe traumatic brain injury. J Neurotrauma. 2007;24:1699\u2013706.","journal-title":"J Neurotrauma"},{"key":"1037_CR23","volume-title":"Fibrinolytic activation in patients with progressive intracranial hemorrhage after traumatic brain injury","author":"K Fair","year":"2019","unstructured":"Fair K, Farrell D, McCully B, Rick E, Dewey EN, Hilliard C, et al. Fibrinolytic activation in patients with progressive intracranial hemorrhage after traumatic brain injury. New York: Mary Ann Liebert Inc.; 2019."},{"key":"1037_CR24","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.jss.2014.08.016","volume":"193","author":"A Briggs","year":"2015","unstructured":"Briggs A, Gates JD, Kaufman RM, Calahan C, Gormley WB, Havens JM. Platelet dysfunction and platelet transfusion in traumatic brain injury. J Surg Res. 2015;193:802\u20136.","journal-title":"J Surg Res"},{"key":"1037_CR25","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.ajem.2017.04.020","volume":"35","author":"H Wang","year":"2017","unstructured":"Wang H, Cao H, Zhang X, Ge L, Bie L. The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients. Am J Emerg Med. 2017;35:1404\u20137.","journal-title":"Am J Emerg Med"},{"key":"1037_CR26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/00003246-199801000-00031","volume":"26","author":"RU Scherer","year":"1998","unstructured":"Scherer RU, Spangenberg P. Procoagulant activity in patients with isolated severe head trauma. Crit Care Med. 1998;26:149\u201356.","journal-title":"Crit Care Med."},{"key":"1037_CR27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/00008506-200101000-00010","volume":"13","author":"B Grenander","year":"2001","unstructured":"Grenander B, Bredbacka S, Rydvall A, \u00c1roch R, Edner G, Koskinen LOD, et al. Antithrombin treatment in patients with traumatic brain injury: a pilot study. J Neurosurg Anesthesiol. 2001;13:49\u201356.","journal-title":"J Neurosurg Anesthesiol"},{"key":"1037_CR28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/00008506-199404000-00002","volume":"6","author":"S Bredbacka","year":"1994","unstructured":"Bredbacka S, Edner G. Soluble fibrin and D-dimer as detectors of hypercoagulability in patients with isolated brain trauma. J Neurosurg Anesthesiol. 1994;6:75\u201382.","journal-title":"J Neurosurg Anesthesiol"},{"key":"1037_CR29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/TA.0b013e318256deab","volume":"73","author":"ME Kutcher","year":"2012","unstructured":"Kutcher ME, Redick BJ, McCreery RC, Crane IM, Greenberg MD, Cachola LM, et al. Characterization of platelet dysfunction after trauma. J Trauma Acute Care Surg. 2012;73:13\u20139.","journal-title":"J Trauma Acute Care Surg"},{"key":"1037_CR30","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1136\/jnnp.38.6.567","volume":"38","author":"CJ Vecht","year":"1975","unstructured":"Vecht CJ, Sibinga CT, Minderhoud JM. Disseminated intravascular coagulation and head injury. J Neurol Neurosurg Psychiatry. 1975;38:567\u201371.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1037_CR31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/BF01809225","volume":"43","author":"L Auer","year":"1978","unstructured":"Auer L. Disturbances of the coagulatory system in patients with severe cerebral trauma. I. Acta Neurochir. 1978;43:51\u20139.","journal-title":"Acta Neurochir"},{"key":"1037_CR32","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/01.TA.0000159249.68363.78","volume":"58","author":"M Carrick","year":"2005","unstructured":"Carrick M, Tyroch A, Youens C, Handley T. Subsequent development of thrombocytopenia and coagulopathy in moderate and severe head injury: support for serial laboratory examination. J Trauma. 2005;58:725\u20139.","journal-title":"J Trauma"},{"key":"1037_CR33","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1001\/archsurg.1996.01430210021004","volume":"131","author":"F Hulka","year":"1996","unstructured":"Hulka F, Mullins RJ, Frank EH. Blunt brain injury activates the coagulation process. Arch Surg. 1996;131:923\u20137 (discussion 927\u20138).","journal-title":"Arch Surg"},{"key":"1037_CR34","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1089\/neu.2005.22.291","volume":"22","author":"M Engstr\u00f6m","year":"2005","unstructured":"Engstr\u00f6m M, Romner B, Schal\u00e9n W, Reinstrup P. Thrombocytopenia predicts progressive hemorrhage after head trauma. J Neurotrauma. 2005;22:291\u20136.","journal-title":"J Neurotrauma"},{"key":"1037_CR35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1227\/00006123-198610000-00005","volume":"19","author":"H Touho","year":"1986","unstructured":"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;19:523\u201331.","journal-title":"Neurosurgery"},{"key":"1037_CR36","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1080\/02699052.2018.1536805","volume":"32","author":"AR Guillotte","year":"2018","unstructured":"Guillotte AR, Herbert JP, Madsen R, Hammer RD, Litofsky NS. Effects of platelet dysfunction and platelet transfusion on outcomes in traumatic brain injury patients. Brain Inj. 2018;32:1849\u201357.","journal-title":"Brain Inj"},{"key":"1037_CR37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fneur.2018.00015","volume":"9","author":"C Lindblad","year":"2018","unstructured":"Lindblad C, Thelin EP, Nekludov M, Frostell A, Nelson DW, Svensson M, et al. Assessment of platelet function in traumatic brain injury-A retrospective observational study in the neuro-critical care setting. Front Neurol. 2018;9:15.","journal-title":"Front Neurol"},{"key":"1037_CR38","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1136\/jcp.28.10.814","volume":"28","author":"CJ Vecht","year":"1975","unstructured":"Vecht CJ, Minderhoud JM, Sibinga CT. Platelet aggregability in relation to impaired consciousness after head injury. J Clin Pathol. 1975;28:814\u201320.","journal-title":"J Clin Pathol"},{"key":"1037_CR39","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1089\/neu.2008.0548","volume":"25","author":"CH Halpern","year":"2008","unstructured":"Halpern CH, Reilly PM, Turtz AR, Stein SC. Traumatic coagulopathy: the effect of brain injury. J Neurotrauma. 2008;25:997\u20131001.","journal-title":"J Neurotrauma"},{"key":"1037_CR40","doi-asserted-by":"crossref","unstructured":"Pahatouridis D, Alexiou GA, Zigouris A, Mihos E, Drosos D, Voulgaris S. Brain injury coagulopathy in moderate head injury. The role of early administration of low molecular weight heparin. 2010;","DOI":"10.3109\/02699052.2010.490510"},{"key":"1037_CR41","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1089\/neu.2006.0173","volume":"24","author":"M Nekludov","year":"2007","unstructured":"Nekludov M, Antovic J, Bredbacka S, Blomb\u00e4ck M. Coagulation abnormalities associated with severe isolated traumatic brain injury: cerebral arterio-venous differences in coagulation and inflammatory markers. J Neurotrauma. 2007;24:174\u201380.","journal-title":"J Neurotrauma"},{"key":"1037_CR42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3109\/00365519309092568","volume":"53","author":"JV S\u00f8rensen","year":"2009","unstructured":"S\u00f8rensen JV, Jensen HP, Rahr HB, Borris LC, Lassen MR, Fedders O, et al. Haemostatic activation in patients with head injury with and without simultaneous multiple trauma. Scand J Clin Lab Invest. 2009;53:659\u201365.","journal-title":"Scand J Clin Lab Invest"},{"key":"1037_CR43","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1097\/00005373-199906000-00018","volume":"46","author":"S Gando","year":"1999","unstructured":"Gando S, Nanzaki S, Kemmotsu O. Coagulofibrinolytic changes after isolated head injury are not different from those in trauma patients without head injury. J Trauma. 1999;46:1070\u20136 (discussion 1076\u20137).","journal-title":"J Trauma."},{"key":"1037_CR44","first-page":"PC01","volume":"8","author":"HMA Foaud","year":"2014","unstructured":"Foaud HMA, Labib JR, Metwally HG, El-Twab KMA. Plasma D-dimer as a prognostic marker in ICU admitted Egyptian children with traumatic brain injury. J Clin Diagn Res. 2014;8:PC01\u20136.","journal-title":"J Clin Diagn Res"},{"key":"1037_CR45","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2176\/nmc.oa.2018-0254","volume":"59","author":"E Suehiro","year":"2019","unstructured":"Suehiro E, Fujiyama Y, Kiyohira M, Motoki Y, Nojima J, Suzuki M. Probability of soluble tissue factor release lead to the elevation of d-dimer as a biomarker for traumatic brain injury. Neurol Med Chir (Tokyo). 2019;59:63\u20137.","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"1037_CR46","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/SHK.0000000000000912","volume":"48","author":"J Karri","year":"2017","unstructured":"Karri J, Cardenas JC, Matijevic N, Wang YW, Choi S, Zhu L, et al. Early fibrinolysis associated with hemorrhagic progression following traumatic brain injury. Shock. 2017;48:644\u201350.","journal-title":"Shock"},{"key":"1037_CR47","doi-asserted-by":"crossref","unstructured":"Defazio M V., Rammo RA, Robles JR, Bramlett HM, Dietrich WD, Bullock MR. The potential utility of blood-derived biochemical markers as indicators of early clinical trends following severe traumatic brain injury. World Neurosurg. 2014. p. 151\u20138.","DOI":"10.1016\/j.wneu.2013.01.015"},{"issue":"Suppl 3","key":"1037_CR48","doi-asserted-by":"crossref","first-page":"S197","DOI":"10.1007\/PL00014355","volume":"158","author":"S Becker","year":"1999","unstructured":"Becker S, Schneider W, Kreuz W, Jacobi G, Scharrer I, Nowak-G\u00f6ttl U. Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma. Eur J Pediatr. 1999;158(Suppl 3):S197\u2013202.","journal-title":"Eur J Pediatr"},{"key":"1037_CR49","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1097\/SLA.0000000000003464","volume":"270","author":"CM Leeper","year":"2019","unstructured":"Leeper CM, Strotmeyer SJ, Neal MD, Gaines BA. Window of opportunity to mitigate trauma-induced coagulopathy: fibrinolysis shutdown not prevalent until 1 hour post-injury. Ann Surg. 2019;270:528\u201334.","journal-title":"Ann Surg"},{"key":"1037_CR50","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1097\/SLA.0000000000002355","volume":"266","author":"CM Leeper","year":"2017","unstructured":"Leeper CM, Neal MD, McKenna CJ, Gaines BA. Trending fibrinolytic dysregulation: fibrinolysis shutdown in the days after injury is associated with poor outcome in severely injured children. Ann Surg. 2017;266:508\u201315.","journal-title":"Ann Surg"},{"key":"1037_CR51","doi-asserted-by":"crossref","first-page":"R2","DOI":"10.1186\/cc9399","volume":"15","author":"S Greuters","year":"2011","unstructured":"Greuters S, van den Berg A, Franschman G, Viersen VA, Beishuizen A, Peerdeman SM, et al. Acute and delayed mild coagulopathy are related to outcome in patients with isolated traumatic brain injury. Crit Care. 2011;15:R2.","journal-title":"Crit Care"},{"key":"1037_CR52","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1016\/j.injury.2012.04.013","volume":"43","author":"A Homnick","year":"2012","unstructured":"Homnick A, Sifri Z, Yonclas P, Mohr A, Livingston D. The temporal course of intracranial haemorrhage progression: How long is observation necessary? Injury. 2012;43:2122\u20135.","journal-title":"Injury"},{"key":"1037_CR53","doi-asserted-by":"crossref","unstructured":"Tynng\u00e5rd N, Lindahl TL, Ramstr\u00f6m S. Assays of different aspects of haemostasis - what do they measure? Thromb J 2015.","DOI":"10.1186\/s12959-015-0036-2"},{"key":"1037_CR54","doi-asserted-by":"crossref","unstructured":"Vulliamy P, Kornblith LZ, Kutcher ME, Cohen MJ, Brohi K, Neal MD. Alterations in platelet behavior after major trauma: adaptive or maladaptive? Platelets 2020. p. 1\u201310.","DOI":"10.1080\/09537104.2020.1718633"},{"key":"1037_CR55","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/00005373-200110000-00003","volume":"51","author":"RC Jacoby","year":"2001","unstructured":"Jacoby RC, Owings JT, Holmes J, Battistella FD, Gosselin RC, Paglieroni TG. Platelet activation and function after trauma. J Trauma. 2001;51:639\u201347.","journal-title":"J Trauma"},{"key":"1037_CR56","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/TA.0000000000002140","volume":"86","author":"CC Verni","year":"2019","unstructured":"Verni CC, Davila A, Balian S, Sims CA, Diamond SL. Platelet dysfunction during trauma involves diverse signaling pathways and an inhibitory activity in patient-derived plasma. J Trauma Acute Care Surg. 2019;86:250\u20139.","journal-title":"J Trauma Acute Care Surg"},{"key":"1037_CR57","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12028-014-0051-3","volume":"22","author":"AM Massaro","year":"2015","unstructured":"Massaro AM, Doerfler S, Nawalinski K, Michel B, Driscoll N, Ju C, et al. Thromboelastography defines late hypercoagulability after TBI: a pilot study. Neurocrit Care. 2015;22:45\u201351.","journal-title":"Neurocrit Care"},{"key":"1037_CR58","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1227\/01.NEU.0000108641.98845.88","volume":"54","author":"SC Stein","year":"2004","unstructured":"Stein SC, Graham DI, Chen X-H, Smith DH. Association between intravascular microthrombosis and cerebral ischemia in traumatic brain injury. Neurosurgery. 2004;54:687\u201391 (discussion 691).","journal-title":"Neurosurgery"},{"key":"1037_CR59","first-page":"19","volume-title":"Hemorrhagic progression of a contusion after traumatic brain injury: a review","author":"D Kurland","year":"2012","unstructured":"Kurland D, Hong C, Aarabi B, Gerzanich V, Simard JM. Hemorrhagic progression of a contusion after traumatic brain injury: a review. New York: Mary Ann Liebert, Inc.; 2012. p. 19\u201331."},{"key":"1037_CR60","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1097\/TA.0000000000002047","volume":"85","author":"E Furay","year":"2018","unstructured":"Furay E, Daley M, Teixeira PG, Coopwood TB, Aydelotte JD, Malesa N, et al. Goal-directed platelet transfusions correct platelet dysfunction and may improve survival in patients with severe traumatic brain injury. J Trauma Acute Care Surg. 2018;85:881\u20137.","journal-title":"J Trauma Acute Care Surg"},{"key":"1037_CR61","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1089\/neu.2014.3728","volume":"32","author":"DY Kim","year":"2015","unstructured":"Kim DY, O\u2019Leary M, Nguyen A, Kaji A, Bricker S, Neville A, et al. The effect of platelet and desmopressin administration on early radiographic progression of traumatic intracranial hemorrhage. J Neurotrauma. 2015;32:1815\u201321.","journal-title":"J Neurotrauma"},{"key":"1037_CR62","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/TA.0000000000002521","volume":"88","author":"EJ Furay","year":"2020","unstructured":"Furay EJ, Daley MJ, Satarasinghe P, Lara S, Aydelotte JD, Teixeira PG, et al. Desmopressin is a transfusion sparing option to reverse platelet dysfunction in patients with severe traumatic brain injury. J Trauma Acute Care Surg. 2020;88:80\u20136.","journal-title":"J Trauma Acute Care Surg"},{"key":"1037_CR63","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s13054-017-1808-9","volume":"21","author":"T Wada","year":"2017","unstructured":"Wada T, Gando S, Maekaw K, Katabami K, Sageshima H, Hayakawa M, et al. Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury. Crit Care. 2017;21:219.","journal-title":"Crit Care"},{"key":"1037_CR64","doi-asserted-by":"crossref","unstructured":"Duguid J, O\u2019Shaughnessy DF, Atterbury C, Maggs PB, Murphy M, Thomas D, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br. J. Haematol. 2004. p. 11\u201328.","DOI":"10.1111\/j.1365-2141.2004.04972.x"},{"key":"1037_CR65","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.surg.2016.08.023","volume":"161","author":"R Chang","year":"2017","unstructured":"Chang R, Folkerson LE, Sloan D, Tomasek JS, Kitagawa RS, Choi HA, et al. Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage. Surgery. 2017;161:538\u201345.","journal-title":"Surgery"},{"key":"1037_CR66","doi-asserted-by":"crossref","unstructured":"Joseph B, Amini A, Friese RS, Houdek M, Hays D, Kulvatunyou N, et al. Factor IX complex for the correction of traumatic coagulopathy. J Trauma Acute Care Surg. 2012. p. 828\u201334.","DOI":"10.1097\/TA.0b013e318247c944"},{"key":"1037_CR67","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.jemermed.2012.12.022","volume":"44","author":"J Ferreira","year":"2013","unstructured":"Ferreira J, Delossantos M. The clinical use of prothrombin complex concentrate. J Emerg Med. 2013;44:1201\u201310.","journal-title":"J Emerg Med"},{"key":"1037_CR68","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1227\/01.neu.0000316898.78371.74","volume":"62","author":"RK Narayan","year":"2008","unstructured":"Narayan RK, Maas AIR, Marshall LF, Servadei F, Skolnick BE, Tillinger MN. Recombinant factor viia in traumatic intracerebral hemorrhage: Results of a dose-escalation clinical trial. Neurosurgery. 2008;62:776\u201386.","journal-title":"Neurosurgery"},{"key":"1037_CR69","doi-asserted-by":"crossref","unstructured":"Longstaff C. Measuring fibrinolysis: from research to routine diagnostic assays. J Thromb Haemost 2018. p. 652\u201362.","DOI":"10.1111\/jth.13957"},{"key":"1037_CR70","doi-asserted-by":"crossref","unstructured":"Ramos CR, Moore EE, Manco-Johnson ML, Silliman CC, Chapman MC, Banerjee A. The incidence and magnitude of fibrinolytic activation in trauma patients: a rebuttal. J Thromb Haemost 2013; p. 1435\u20137.","DOI":"10.1111\/jth.12240"},{"key":"1037_CR71","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/jth.12078","volume":"11","author":"I Raza","year":"2013","unstructured":"Raza I, Davenport R, Rourke C, Platton S, Manson J, Spoors C, et al. The incidence and magnitude of fibrinolytic activation in trauma patients. J Thromb Haemost. 2013;11:307\u201314.","journal-title":"J Thromb Haemost"},{"key":"1037_CR72","doi-asserted-by":"crossref","unstructured":"CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394:1713\u201323.","DOI":"10.1016\/S0140-6736(19)32233-0"},{"key":"1037_CR73","doi-asserted-by":"crossref","unstructured":"Olufajo OA, Yorkgitis BK, Cooper Z, Rios-Diaz A, Metcalfe D, Havens JM, et al. How long should we fear? Long-term risk of venous thromboembolism in patients with traumatic brain injury. J Trauma Acute Care Surg. Lippincott Williams and Wilkins; 2016. p. 71\u20137.","DOI":"10.1097\/TA.0000000000001046"},{"key":"1037_CR74","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jamcollsurg.2016.12.018","volume":"224","author":"JP Meizoso","year":"2017","unstructured":"Meizoso JP, Karcutskie CA, Ray JJ, Namias N, Schulman CI, Proctor KG. Persistent fibrinolysis shutdown is associated with increased mortality in severely injured trauma patients. J Am Coll Surg. 2017;224:575\u201382.","journal-title":"J Am Coll Surg"},{"key":"1037_CR75","first-page":"1147","volume":"74","author":"JR Hay","year":"2015","unstructured":"Hay JR, Johnson VE, Young AMH, Smith DH, Stewart W. Blood-brain barrier disruption is an early event that may persist for many years after traumatic brain injury in humans. J Neuropathol Exp Neurol Oxford Academic. 2015;74:1147\u201357.","journal-title":"J Neuropathol Exp Neurol Oxford Academic"},{"key":"1037_CR76","first-page":"261825","volume":"2015","author":"D Zhang","year":"2015","unstructured":"Zhang D, Gong S, Jin H, Wang J, Sheng P, Zou W, et al. Coagulation parameters and risk of progressive hemorrhagic injury after traumatic brain injury: a systematic review and meta-analysis. Biomed Res Int. 2015;2015:261825.","journal-title":"Biomed Res Int"},{"key":"1037_CR77","first-page":"189","volume":"20","author":"M Spatz","year":"1978","unstructured":"Spatz M, Micic D, Mrsulja BB, Klatzo I. Cerebral microvessels as mediators of cerebral transport. Adv Neurol. 1978;20:189\u201396.","journal-title":"Adv Neurol"},{"key":"1037_CR78","doi-asserted-by":"crossref","unstructured":"Levi M, Van Der Poll T, Schultz M. Systemic versus localized coagulation activation contributing to organ failure in critically ill patients. Semin Immunopathol Springer; 2012. p. 167\u201379.","DOI":"10.1007\/s00281-011-0283-7"},{"key":"1037_CR79","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1055\/s-0033-1357490","volume":"39","author":"GJ Del Zoppo","year":"2013","unstructured":"Del Zoppo GJ, Izawa Y, Hawkins BT. Hemostasis and alterations of the central nervous system. Semin Thromb Hemost. 2013;39:856\u201375.","journal-title":"Semin Thromb Hemost"},{"key":"1037_CR80","doi-asserted-by":"crossref","first-page":"484","DOI":"10.5271\/sjweh.3082","volume":"36","author":"L Rollin","year":"2010","unstructured":"Rollin L, Darmoni S, Caillard JF, Gehanno JF. Searching for high-quality articles about intervention studies in occupational health\u2014What is really missed when using only the Medline database? Scand J Work Environ Heal. 2010;36:484\u20137.","journal-title":"Scand J Work Environ Heal"}],"container-title":["Neurocritical Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-020-01037-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12028-020-01037-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12028-020-01037-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T19:45:02Z","timestamp":1624995902000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12028-020-01037-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":80,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["1037"],"URL":"https:\/\/doi.org\/10.1007\/s12028-020-01037-8","relation":{},"ISSN":["1541-6933","1556-0961"],"issn-type":[{"value":"1541-6933","type":"print"},{"value":"1556-0961","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]},"assertion":[{"value":"30 June 2020","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Marc Maegele has received honoraria for speaker\u00b4s bureaus, participation in advisory board meetings and congress travel support from IL-Werfen\/TEM International and Haemonetics. BMB has received speaker\u2019s fees from CSL Behring. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"We confirm that authorship requirements have been met and the final manuscript was approved by all authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}]}}