Prehospital Plasma GFAP Analyzed as Stroke Biomarker

Emergency medical services (EMS) encountering patients with acute stroke symptoms are challenged with the difficult task of rapidly triaging the patient to the appropriate hospital with sufficient therapeutic capabilities.

Glial fibrillary acidic protein (GFAP) and tau are differentially released in ischemic and hemorrhagic stroke (HS), but their very early release dynamics are unknown, as previous studies have focused on single-time point measurements after hospital admission. Circulating GFAP was increased in only 36% of patients with intracerebral hemorrhage (ICH).

Clinical Neuroscientists at the Helsinki University Hospital (Helsinki, Finland) and their colleagues performed ultra-sensitivite single-molecule array measurements of plasma GFAP and total tau in a stroke code patient cohort with cardinal stroke symptoms. Sequential sampling included two ultra-early samples and a follow-up sample on the next morning. The team included 272 cases (203 acute cerebral ischemia [ACI], 60 HS, and nine stroke mimics).

The investigators performed plasma GFAP and total tau (T-tau) measurements using commercially available GFAP Discovery and Tau 2.0 kits on the Simoa HD-1 Analyzer, (Quanterix, Billerica, MA, USA). The median (IQR) last-known-well to sampling time was 53 (35–90) minutes for initial prehospital samples, 90 (67–130) minutes for secondary acute samples, and 21 (16–24) hours for next morning samples.

The scientists reported that the plasma GFAP was significantly higher in patients with HS than ACI (P < 0.001 for <1 hour and <3 hour prehospital samples, and <3 hour secondary samples), while total tau showed no intergroup difference. The prehospital GFAP release rate (pg/mL/minute) occurring between the two very early samples was significantly higher in patients with HS than ACI [2.4 (0.6–14.1)] versus 0.3 (0.3–0.9) pg/mL/minute. For cases with <3 hour prehospital sampling (ACI n = 178, HS n = 59), a combined rule (prehospital GFAP >410 pg/mL, or prehospital GFAP 90–410 pg/mL together with GFAP release >0.6 pg/mL/minute) enabled ruling out HS with high certainty (NPV 98.4%) in 68% of patients with ACI (sensitivity for HS 96.6%, specificity 68%, PPV 50%).

The authors concluded that their study demonstrated that when sufficiently sensitive assay technology is applied, the very early prehospital GFAP plasma concentration and its prehospital release rate can in combination provide improved differential diagnosis of patients with ACI and HS. GFAP ruled out HS in two-thirds of patients with ACI with high certainty, with improved performance in cases with moderate to severe stroke symptoms. The study was published on August 12, 2021 in the journal Clinical Chemistry.

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