Whole-blood point-of-care glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 biomarkers after traumatic brain injury in the US: a prospective diagnostic prediction of intracranial injury on head CT.

BACKGROUND: Biomarkers like glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) are being globally recommended as a valuable component in the evaluation of acute TBI. Having a regulatory-approved whole-blood test is imperative to provide consistent and democratized approach to healthcare. This prospective, national multicenter cohort trial (NCT04171960) evaluated the performance of a whole-blood, point-of-care (POC) GFAP/UCH-L1 panel in determining need for head computed tomography (CT) in adult patients presenting to the emergency department (ED) with suspected traumatic brain injury (TBI). METHODS: Adults presenting to the ED with suspected TBI, Glasgow Coma Scale score 13-15, completed head CT scan, and blood collected within 24 h of injury were included. GFAP and UCH-L1 measured in whole-blood through a POC TBI biomarker test were analyzed using prespecified cutoffs and combined into a single test result and compared with CT findings. FINDINGS: 970 enrolled participants [mean age 46.8 (18-97); 36%female; 69%White, 18%Black; 19%Hispanic/Latino] were analyzed. 683 participants (70.4%) had 'elevated' and 287 (29.6%) had 'not elevated' TBI blood test result. For detection of CT intracranial injury, the whole-blood TBI test had sensitivity of 96.5% (95%CI 93.6-98.1%) and NPV 96.5% (95%CI 93.7-98.1%). INTERPRETATION: The GFAP/UCH-L1 whole-blood test had high sensitivity and NPV for prediction of intracranial injury within 24 h of TBI. The platform received U.S.-FDA clearance and expands clinical use of the TBI test beyond the laboratory. This test provides results in 15 min; supporting rapid triage and decision-making in suspected TBI. FUNDING: Defense Health Agency (DHA) under Contract No. W81XWH19C0071.