Diagnostic Accuracy of GFAP and UCH-L1 for Acute Intracranial Trauma in a Predominantly Blast-Exposed Cohort of Combat Casualties

Importance There is an urgent need for objective blood tests to guide triage of suspected traumatic brain injury (TBI) in far-forward combat environments, where blast exposure is common and neuroimaging is frequently unavailable. Blood-based glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) are transforming triage of suspected TBI due to their 99% negative predictive value for ruling out acute intracranial trauma in civilian impact TBI. However, accuracy in military blast-dominant TBI is unclear. Objective To determine accuracy of day-of-injury serum or plasma GFAP and UCH-L1 levels for ruling-out acute intracranial trauma in a sequential real-world cohort of combat casualties. Design Retrospective cohort study leveraging existing data from a clinical laboratory validation protocol that processed and stored leftover day-of-injury clinical samples from evacuated combat casualties between January 1, 2024, and February 6, 2025 for subsequent analysis for GFAP and UCH-L1 using FDA-cleared assay thresholds. Setting Single-center, tertiary referral trauma center. Participants Day-of-injury plasma or serum GFAP and UCH-L1 levels were available for 137 combat casualties. The cohort was 99.3% male with a median age of 21.8 years; 75.2% sustained blast-related injuries. Most (92.7%) had blood collected within 6 hours of injury. Exposure Serum or plasma GFAP and UCH-L1 measured with Abbott Alinity-i or i-STAT TBI assays. Elevation was defined as GFAP [≥]35 pg/mL or UCH-L1 [≥]400 pg/mL on Alinity-i, and GFAP [≥]30 pg/mL or UCH-L1 [≥]360 pg/mL on i-STAT. Main Outcomes and Measures Accuracy of biomarker elevation for ruling-out intracranial trauma on head CT, including sensitivity, specificity, and negative predictive value (NPV). Results Among 137 casualties, 83 (60.6%) were biomarker-elevated. Sixteen participants (11.7%) had CT-confirmed intracranial trauma, of whom 15 were biomarker-elevated, yielding 93.8% sensitivity and 98.2% NPV, and 43.8% specificity. Twenty-three participants (16.8%) had intracranial trauma and/or head/face/c-spine fracture; 21 were biomarker-elevated, corresponding to 91.3% sensitivity, 96.3% NPV, and 45.6% specificity. Conclusions and Relevance In this real-world cohort of blast-dominant combat casualties, day-of-injury GFAP and UCH-L1 demonstrated high NPV and sensitivity for intracranial trauma, with modest specificity. These findings support the utility of GFAP and UCH-L1 to aid early triage and decision-making in blast-dominant military TBI.