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Extended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysis

2021; Springer Science+Business Media; Volume: 36; Issue: 3 Linguagem: Inglês

10.1007/s12028-021-01400-3

1556-0961

Julia K. Böhm, Victoria Schaeben, Nadine Schäfer, Helge Güting, Rolf Lefering, Sophie Thorn, Herbert Schöchl, Johannes Zipperle, Oliver Grottke, Rolf Rossaint, Simon Stanworth, Nicola Curry, Marc Maegele, Cecilia Åkerlund, Krisztina Amrein, Nada Anđelić, Lasse Andreassen, Audny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo‐Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Bražinová, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, András Büki, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Iris Ceyisakar, Hans Clusmann, Mark Coburn, Jonathan Coles, D. James Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot‐Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Françesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens P. Dreier, Guy‐Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gómez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin J. O. Kompanje, Daniel Kondziella, Evgenios Koraropoulos, Lars‐Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valérie Legrand, Aurélie Lejeune, Leon Levi, Roger Lightfoot, Hester F. Lingsma, Andrew I.R. Maas, Ana M. Castaño‐León, Marc Maegele, Marek Majdán, Alex Manara, Geoffrey T. Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, David Menon, Tomas Menovsky, Ana Mikolić, Benoît Misset, Visakh Muraleedharan, Lynnette Murray, Ancuța Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Matej Orešič, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean‐François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco C. Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Pleș, Suzanne Polinder, Iñigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan R. Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Ročka, Cecilie Røe, Olav Røise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusňák, Juan Sahuquillo, Oliver Sakowitz, Renán Sánchez-Porras, János Sándor, Nadine Schäfer, Silke Schmidt, Herbert Schöechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel A. Stamatakis, Simon Stanworth, Robert D. Stevens, William Stewart, Ewout W. Steyerberg, Nino Stocchetti, Nina Sundström, Anneliese Synnot, Riikka Takala, Viktória Tamás, Tomas Tamošuitis, Mark Taylor, Braden Te Ao, Olli Tenovuo, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vuleković, Kevin Wang, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle,

Trauma, Hemostasis, Coagulopathy, Resuscitation

Abstract Background Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury. Methods Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) ( n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick’s value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers. Results Patients with iTBI with INR ≥ 1.2 ( n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 ( n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15–20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2. Conclusions This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.