A Novel Combination of Blood Biomarkers and Clinical Stroke Scales Facilitates Detection of Large Vessel Occlusion Ischemic Strokes

Gaude, Edoardo; Nogueira, Barbara; Ladreda Mochales, Marcos; Graham, Sheila; Smith, Sarah; Shaw, Lisa; Graziadio, Sara; Ladreda Mochales, Gonzalo; Sloan, Philip; Bernstock, Joshua D.; Shekhar, Shashank; Gropen, Toby I.; Price, Christopher I.

Acute ischemic stroke caused by large vessel occlusions (LVOs) is a major contributor to stroke deaths and disabilities; however, identification for emergency treatment is challenging. We recruited two separate cohorts of suspected stroke patients and screened a panel of blood-derived protein biomarkers for LVO detection. Diagnostic performance was estimated by using blood biomarkers in combination with NIHSS-derived stroke severity scales. Multivariable analysis demonstrated that D-dimer (OR 16, 95% CI 5–60; p-value < 0.001) and GFAP (OR 0.002, 95% CI 0–0.68; p-value < 0.05) comprised the optimal panel for LVO detection. Combinations of D-dimer and GFAP with a number of stroke severity scales increased the number of true positives, while reducing false positives due to hemorrhage, as compared to stroke scales alone (p-value < 0.001). A combination of the biomarkers with FAST-ED resulted in the highest accuracy at 95% (95% CI: 87–99%), with sensitivity of 91% (95% CI: 72–99%), and specificity of 96% (95% CI: 90–99%). Diagnostic accuracy was confirmed in an independent cohort, in which accuracy was again shown to be 95% (95% CI: 87–99%), with a sensitivity of 82% (95% CI: 57–96%), and specificity of 98% (95% CI: 92–100%). Accordingly, the combination of D-dimer and GFAP with stroke scales may provide a simple and highly accurate tool for identifying LVO patients, with a potential impact on time to treatment.