TY - JOUR
T1 - Extended Coagulation Profiling in Isolated Traumatic Brain Injury
T2 - A CENTER-TBI Analysis
AU - Böhm, Julia K.
AU - Schaeben, Victoria
AU - Schäfer, Nadine
AU - Güting, Helge
AU - Lefering, Rolf
AU - Thorn, Sophie
AU - Schöchl, Herbert
AU - Zipperle, Johannes
AU - Grottke, Oliver
AU - Rossaint, Rolf
AU - Stanworth, Simon
AU - Curry, Nicola
AU - Maegele, Marc
AU - Åkerlund, Cecilia
AU - Amrein, Krisztina
AU - Andelic, Nada
AU - Andreassen, Lasse
AU - Anke, Audny
AU - Antoni, Anna
AU - Audibert, Gérard
AU - Azouvi, Philippe
AU - Azzolini, Maria Luisa
AU - Bartels, Ronald
AU - Barzó, Pál
AU - Beauvais, Romuald
AU - Beer, Ronny
AU - Bellander, Bo Michael
AU - Belli, Antonio
AU - Benali, Habib
AU - Berardino, Maurizio
AU - Beretta, Luigi
AU - Blaabjerg, Morten
AU - Bragge, Peter
AU - Brazinova, Alexandra
AU - Brinck, Vibeke
AU - Brooker, Joanne
AU - Brorsson, Camilla
AU - Buki, Andras
AU - Bullinger, Monika
AU - Cabeleira, Manuel
AU - Caccioppola, Alessio
AU - Calappi, Emiliana
AU - Calvi, Maria Rosa
AU - Cameron, Peter
AU - Lozano, Guillermo Carbayo
AU - Carbonara, Marco
AU - Cavallo, Simona
AU - Chevallard, Giorgio
AU - Chieregato, Arturo
AU - Ylén, Peter
AU - CENTER-TBI investigators and participants
N1 - © 2021. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CENTER-TBI
KW - Coagulopathy
KW - Fibrin monomers
KW - Progressive intracranial hemorrhage
KW - Thrombin generation
KW - Traumatic brain injury
KW - Blood Coagulation Disorders
KW - Prospective Studies
KW - Humans
KW - Protein C
KW - Thrombin
KW - Brain Injuries, Traumatic/epidemiology
KW - Plasminogen
UR - http://www.scopus.com/inward/record.url?scp=85130632463&partnerID=8YFLogxK
U2 - 10.1007/s12028-021-01400-3
DO - 10.1007/s12028-021-01400-3
M3 - Article
C2 - 34918214
AN - SCOPUS:85130632463
SN - 1541-6933
VL - 36
SP - 927
EP - 941
JO - Neurocritical Care
JF - Neurocritical Care
IS - 3
ER -