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

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aut.relation.journalNeurocritical Careen_NZ
aut.researcherJones, Kelly
dc.contributor.authorBöhm, JKen_NZ
dc.contributor.authorSchaeben, Ven_NZ
dc.contributor.authorSchäfer, Nen_NZ
dc.contributor.authorGüting, Hen_NZ
dc.contributor.authorLefering, Ren_NZ
dc.contributor.authorThorn, Sen_NZ
dc.contributor.authorSchöchl, Hen_NZ
dc.contributor.authorZipperle, Jen_NZ
dc.contributor.authorGrottke, Oen_NZ
dc.contributor.authorRossaint, Ren_NZ
dc.contributor.authorStanworth, Sen_NZ
dc.contributor.authorCurry, Nen_NZ
dc.contributor.authorMaegele, Men_NZ
dc.contributor.authorÅkerlund, Cen_NZ
dc.contributor.authorAmrein, Ken_NZ
dc.contributor.authorAndelic, Nen_NZ
dc.contributor.authorAndreassen, Len_NZ
dc.contributor.authorAnke, Aen_NZ
dc.contributor.authorAntoni, Aen_NZ
dc.contributor.authorAudibert, Gen_NZ
dc.contributor.authorAzouvi, Pen_NZ
dc.contributor.authorAzzolini, MLen_NZ
dc.contributor.authorBartels, Ren_NZ
dc.contributor.authorBarzó, Pen_NZ
dc.contributor.authorBeauvais, Ren_NZ
dc.contributor.authorBeer, Ren_NZ
dc.contributor.authorBellander, BMen_NZ
dc.contributor.authorBelli, Aen_NZ
dc.contributor.authorBenali, Hen_NZ
dc.contributor.authorBerardino, Men_NZ
dc.contributor.authorBeretta, Len_NZ
dc.contributor.authorBlaabjerg, Men_NZ
dc.contributor.authorBragge, Pen_NZ
dc.contributor.authorBrazinova, Aen_NZ
dc.contributor.authorBrinck, Ven_NZ
dc.contributor.authorBrooker, Jen_NZ
dc.contributor.authorBrorsson, Cen_NZ
dc.contributor.authorBuki, Aen_NZ
dc.contributor.authorBullinger, Men_NZ
dc.contributor.authorCabeleira, Men_NZ
dc.contributor.authorCaccioppola, Aen_NZ
dc.contributor.authorCalappi, Een_NZ
dc.contributor.authorCalvi, MRen_NZ
dc.contributor.authorCameron, Pen_NZ
dc.contributor.authorLozano, GCen_NZ
dc.contributor.authorCarbonara, Men_NZ
dc.contributor.authorCavallo, Sen_NZ
dc.contributor.authorChevallard, Gen_NZ
dc.contributor.authorChieregato, Aen_NZ
dc.contributor.authorCiterio, Gen_NZ
dc.contributor.authorCeyisakar, Ien_NZ
dc.contributor.authorClusmann, Hen_NZ
dc.contributor.authorCoburn, Men_NZ
dc.contributor.authorColes, Jen_NZ
dc.contributor.authorCooper, JDen_NZ
dc.contributor.authorCorreia, Men_NZ
dc.contributor.authorČović, Aen_NZ
dc.contributor.authorCzeiter, Een_NZ
dc.contributor.authorCzosnyka, Men_NZ
dc.contributor.authorDahyot-Fizelier, Cen_NZ
dc.contributor.authorDark, Pen_NZ
dc.contributor.authorDawes, Hen_NZ
dc.contributor.authorDe Keyser, Ven_NZ
dc.contributor.authorDegos, Ven_NZ
dc.contributor.authorCorte, FDen_NZ
dc.contributor.authorBoogert, HDen_NZ
dc.contributor.authorDepreitere, Ben_NZ
dc.contributor.authorĐilvesi, Đen_NZ
dc.contributor.authorDixit, Aen_NZ
dc.contributor.authorDonoghue, Een_NZ
dc.contributor.authorDreier, Jen_NZ
dc.contributor.authorDulière, GLen_NZ
dc.contributor.authorErcole, Aen_NZ
dc.contributor.authorEsser, Pen_NZ
dc.contributor.authorEzer, Een_NZ
dc.contributor.authorFabricius, Men_NZ
dc.contributor.authorFeigin, VLen_NZ
dc.contributor.authorFoks, Ken_NZ
dc.contributor.authorFrisvold, Sen_NZ
dc.contributor.authorFurmanov, Aen_NZ
dc.contributor.authorGagliardo, Pen_NZ
dc.contributor.authorGalanaud, Den_NZ
dc.contributor.authorGantner, Den_NZ
dc.contributor.authorGao, Gen_NZ
dc.contributor.authorGeorge, Pen_NZ
dc.contributor.authorGhuysen, Aen_NZ
dc.contributor.authorGiga, Len_NZ
dc.contributor.authorGlocker, Ben_NZ
dc.contributor.authorGolubovic, Jen_NZ
dc.contributor.authorGomez, PAen_NZ
dc.contributor.authorGratz, Jen_NZ
dc.contributor.authorGravesteijn, Ben_NZ
dc.contributor.authorGrossi, Fen_NZ
dc.contributor.authorGruen, RLen_NZ
dc.contributor.authorGupta, Den_NZ
dc.contributor.authorHaagsma, JAen_NZ
dc.contributor.authorHaitsma, Ien_NZ
dc.contributor.authorHelbok, Ren_NZ
dc.contributor.authorHelseth, Een_NZ
dc.contributor.authorHorton, Len_NZ
dc.date.accessioned2022-09-05T04:28:32Z
dc.date.available2022-09-05T04:28:32Z
dc.date.copyright2021-01-01en_NZ
dc.date.issued2021-01-01en_NZ
dc.description.abstractBackground: 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.en_NZ
dc.identifier.citationNeurocritical Care 36, 927–941 (2022). https://doi.org/10.1007/s12028-021-01400-3
dc.identifier.doi10.1007/s12028-021-01400-3en_NZ
dc.identifier.issn1541-6933en_NZ
dc.identifier.issn1556-0961en_NZ
dc.identifier.urihttps://hdl.handle.net/10292/15422
dc.publisherSpringer
dc.relation.urihttps://link.springer.com/article/10.1007/s12028-021-01400-3
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessrightsOpenAccessen_NZ
dc.subjectCENTER-TBI; Coagulopathy; Fibrin monomers; Progressive intracranial hemorrhage; Thrombin generation; Traumatic brain injury
dc.titleExtended Coagulation Profiling in Isolated Traumatic Brain Injury: A CENTER-TBI Analysisen_NZ
dc.typeJournal Article
pubs.elements-id475370
pubs.organisational-data/AUT
pubs.organisational-data/AUT/Faculty of Health & Environmental Science
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/National Institute Stroke & Applied Neurosciences
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/National Institute Stroke & Applied Neurosciences/NISAN - Stroke
pubs.organisational-data/AUT/Faculty of Health & Environmental Science/School of Clinical Sciences
pubs.organisational-data/AUT/PBRF
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences
pubs.organisational-data/AUT/PBRF/PBRF Health and Environmental Sciences/HY Public Health & Psychosocial Studies 2018 PBRF
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