Diagnostic Utility of Glial Fibrillary Acidic Protein Beyond 12 Hours After Traumatic Brain Injury: A TRACK-TBI Study

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12 hours (h) of suspected traumatic brain injury (TBI) have been FDA-approved to aid in determining the need for brain computed tomography (CT) scan. The current study was aimed to determine whether this context of use can be expanded beyond 12h post-TBI in patients presenting with Glasgow Coma Scale (GCS) 13-15. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled TBI participants aged ≥17 years who presented to United States Level 1 trauma center and received a clinically indicated brain CT scan within 24h post-injury, a blood draw within 24h and at 14 days for biomarker analysis. Data from participants with emergency department arrival GCS 13-15 and biomarker values at days 1 and 14 were extracted for the primary analysis. A subgroup of hospitalized participants with serial biomarkers at days 1, 3, 5, and 14 were analyzed, including plasma GFAP and UCH-L1, and serum neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B). The primary analysis compared biomarker values dichotomized by head CT results (CT+/CT-). Area under receiver-operating characteristic curve (AUC) was used to determine diagnostic accuracy. The overall cohort included 1142 participants with initial GCS 13-15, with mean age 39.8 years, 65% male, and 73% Caucasian. GFAP provided good discrimination in the overall cohort at days 1 (AUC=0.82) and 14 (AUC=0.72), and in the hospitalized subgroup at days 1 (AUC=0.84), 3 (AUC=0.88), 5 (AUC=0.82), and 14 (AUC=0.74). UCH-L1, NSE, and S100B did not perform well (AUC=0.51-0.57 across timepoints). This study demonstrates the utility of GFAP to aid in decision-making for diagnostic brain CT imaging beyond the 12h timeframe in TBI patients with GCS 13-15.