Objective:We aimed to validate a panel of blood biomarkers to differentiate between ischemic stroke (IS) and intracerebral hemorrhage (ICH) in patients with suspected stroke.Methods:Patients with suspected stroke admitted within 4.5 hours after onset were enrolled. Blood samples were collected at hospital admission. Glial fibrillary acid protein (GFAP), retinol binding protein 4 (RBP-4), N-terminal pro B-type natriuretic peptide (NT-proBNP) and endostatin were measured by immunoassays. Cut-off points were obtained for 100% specificity for IS. A high-sensitivity assay to measure GFAP and rapid point-of-care tests (POCTs) to measure RBP-4 and NT-proBNP were used in subsets of patients. Biomarker panels were evaluated in another cohort of 62 stroke mimics.Results:A total of 189 patients (154 IS and 35 ICH) were enrolled. IS patients had higher RBP-4, NT-proBNP and endostatin and lower GFAP levels than ICH patients. The best biomarker combination for the identification of IS was RBP-4+NT-proBNP, which was able to identify 29.7% of IS patients with 100% specificity. In the subset of patients for whom GFAP was measured with the high-sensitivity assay, RBP-4, NT-proBNP and GFAP identified 51.5% of IS patients with 100% specificity. When stroke mimics were included, specificities were reduced to 98.4 and 96.8%, respectively. POCTs of RBP-4 and NT-proBNP showed results similar results to those of conventional ELISAs.Conclusions:A biomarker panel including RBP-4, NT-proBNP and GFAP provided moderate but potentially useful sensitivity rates at 100% specificity for IS diagnosis. If confirmed in future studies, this strategy might allow pre-hospital treatment in selected patients.Classification of Evidence:This study provides Class I evidence that a biomarker panel including RBP-4, NT-proBNP and GFAP distinguishes IS from ICH with moderate accuracy.==========
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