Association between coagulation biomarkers, intracranial hemorrhage types, and tranexamic acid treatments in early traumatic brain injury

BACKGROUND: Although a prehospital 2 g bolus of tranexamic acid (TXA) has been associated with decreased mortality in patients with traumatic intracranial hemorrhage (ICH), the underlying mechanism remains controversial. We investigated whether early coagulation biomarkers are associated with ICH type, prehospital TXA treatment, and outcomes in patients with early traumatic brain injury (TBI). METHODS: We conducted a secondary analysis of the Prehospital TXA for TBI trial (Glasgow Coma Scale score of <13 and systolic blood pressure of ≥90 mm Hg in patients blindly randomized prehospital to either a 2 g TXA bolus, 1 g TXA bolus plus 1 g TXA infusion, or placebo bolus plus infusion). Intracranial hemorrhage types were categorized as extradural, subdural, subarachnoid, intraventricular, intraparenchymal, mixed, any ICH, and no ICH. Outcomes including Glasgow Outcome Score-Extended, Disability Rating Score, and mortality were examined at discharge and 6 months. Associations between biomarkers, ICH type, TXA treatment group, and outcomes were examined. RESULTS: Of 783 patients, 464 had ICH (5 extradural, 40 subdural, 84 subarachnoid, 7 intraventricular, 26 intraparenchymal, 302 mixed, 464 any ICH), and 319 had no ICH. Three markers of fibrinolytic activity (D-dimer, plasmin-α2-antiplasmin complex [PAP], and thrombin-antithrombin complex [TAT]) were significantly increased in the presence of any ICH and mixed ICH. Higher D-dimer, PAP, and TAT levels were associated with increased mortality, and worse Glasgow Outcome Score-Extended and Disability Rating Score at discharge and 6 months. Plasmin-α2-antiplasmin complex was associated with TXA treatment, with lower PAP levels associated with the higher initial TXA bolus dose. CONCLUSION: In patients with early TBI, D-dimer, PAP, and TAT are associated with the presence of any ICH and mixed ICH. Higher D-dimer, PAP, and TAT levels are associated with neurologic outcomes. Only PAP is associated with TXA treatment. Future studies should examine the utility of PAP as a potential marker for TXA responsiveness. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.