A concerted effort to tackle the global health problem posed by traumatic brain injury (TBI) is long overdue. TBI is a public health challenge of vast, but insufficiently recognised, proportions. Worldwide, more than 50 million people have a TBI each year, and it is estimated that about half the world's population will have one or more TBIs over their lifetime. TBI is the leading cause of mortality in young adults and a major cause of death and disability across all ages in all countries, with a disproportionate burden of disability and death occurring in low-income and middle-income countries (LMICs). It has been estimated that TBI costs the global economy approximately $US400 billion annually. Deficiencies in prevention, care, and research urgently need to be addressed to reduce the huge burden and societal costs of TBI. This Commission highlights priorities and provides expert recommendations for all stakeholders—policy makers, funders, health-care professionals, researchers, and patient representatives—on clinical and research strategies to reduce this growing public health problem and improve the lives of people with TBI.Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Söderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbüchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigator

Summary. Background: Low fibrinogen levels are known to occur in trauma. However, the extent of fibrinogen depletion during trauma hemorrhage, the response to replacement therapy and association with patient outcomes remain unclear. Objectives: The study aims were to: characterize admission fibrinogen level and correlate it with factors associated with injury; describe the time course of fibrinogen depletion and response to replacement therapy; determine the correlation of fibrinogen level with rotational thromboelastography (ROTEM) parameters; evaluate the effect of fibrinogen supplementation ex vivo; and establish the association between fibrinogen level and clinical outcomes. Methods: This was a prospective cohort study of 517 patients. Blood samples were drawn on admission and after admistration of every 4 units of packed red blood cells. Fibrinogen levels were determined with the Clauss method, and global hemostatic competence was assessed with thromboelastometry. The effect of fibrinogen supplementation was assessed in a subgroup of coagulopathic patients. Results: Low admission fibrinogen level was independently associated with injury severity score (P < 0.01), shock (P < 0.001), and prehospital fluid volume (P < 0.001). Fibrinogen supplementation during transfusion maintained but did not augment fibrinogen levels. Administration of cryoprecipitate was associated with improved survival. ROTEM parameters correlated with fibrinogen level, and ex vivo fibrinogen administration reversed coagulopathic ROTEM parameters. Fibrinogen level was an independent predictor of mortality at 24 h and 28 days (P < 0.001). Conclusions: Fibrinogen level is decreased in injured patients on admission and is associated with poor outcomes. ROTEM is a rapid means of assessing hypofibrinogenemia. Earlier administration of specific fibrinogen replacement may improve outcomes, and prospective controlled trials are urgently needed.

In November 2017, the Lancet Neurology Commission on Traumatic Brain Injury (TBI) highlighted existing deficiencies in epidemiology, patient characterization, identifying best practice, outcome assessment, and evidence generation. The Commission concluded that C needed to address deficiencies in prevention , and made a recommendation for large collaborative studies which could provide the framework for precision medicine and comparative effectiveness research (CER).