Prospective Validation of Glial Fibrillary Acidic Protein, d-Dimer, and Clinical Scales for Acute Large-Vessel Occlusion Ischemic Stroke Detection.

Background: Large-vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood-based biomarkers (glial fibrillary acidic protein and d-dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods: The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance-identified stroke code activations <18 hours from symptom onset were recruited at Brandon Regional Hospital (Brandon, FL) between May 2021 and August 2022. Previously determined cutoff concentrations of plasma glial fibrillary acidic protein (213 pg/mL) and d-dimer (600 ng/mL) were used in combination with prehospital stroke scales to detect LVO. We compared rates of LVO detection against a reference standard using computed tomography/magnetic resonance angiography. Results: A total of 382 patients with suspected stroke were recruited. The final cohort was composed of 323 patients with suspected stroke with the following distribution: LVO ischemic stroke (n = 29, 9%), non-LVO ischemic stroke (n = 48, 15%), hemorrhagic stroke (n = 13, 4%), transient ischemic attack (n = 12, 3.9%), and stroke mimics (n = 220, 68.1%). Combining blood-based biomarkers (glial fibrillary acidic protein and d-dimer) with the scale field assessment stroke triage for emergency destination yielded the best performance for LVO detection, with specificity of 94% and sensitivity of 71%. Performance was found to be higher in a subanalysis focusing on patients presenting <6 hours from symptom onset, with 93% specificity and 81% sensitivity. Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage. Conclusion: The present work prospectively validated the potential utility of previously defined glial fibrillary acidic protein and d-dimer cutoff levels (ie, 213 pg/mL and 600 ng/mL, respectively), demonstrating their value for discrimination of LVO stroke from differential diagnoses during code stroke workups. (ClinicalTrials.gov number, NCT04292600.).