GFAP Biomarker Assay Can Discern ICH vs Ischemic Stroke

Glial fibrillary acidic protein (GFAP), a blood biomarker, can be used to rapidly distinguish between hemorrhagic and ischemic stroke, according to a new prospective study. The hope, researchers say, is that point-of-care GFAP testing could one day help triage stroke patients and enable prehospital targeted therapies.

Love-Preet Kalra, MD (RKH Klinikum Ludwigsburg, Germany), who presented the study as an oral abstract at the recent International Stroke Conference in Los Angeles, CA, noted that GFAP already has a role in assessing traumatic brain injuries but has been unwieldy, as testing required use of a centrifuge. In this study, they used the i-STAT Alinity device (Abbott), a portable blood analyzer.

“[Use of] this point-of-care test, which delivers values within 15 minutes, is new. We’ve always performed the measurements on stationary platforms, so we pulled the samples and sent them to bigger labs,” Kalra told TCTMD. With the newer assay, the idea is that emergency medical services (EMS) personnel can simply add a few drops of blood to a cartridge, insert it into a handheld analyzer, see results quickly, then wirelessly transmit that information to the hospital.

For the current study, the research team used blood samples taken in the ambulance but analyzed them at the hospital with the handheld device. Their findings now need to be validated in more patients and more centers, and the feasibility of doing the assay before hospital arrival needs to be assessed, she added. As next steps, “we’ve already started equipping our rescue services with that test,” enrolling around 50 patients so far.

Patients stand to benefit if everything pans out as hoped. For instance, data from the INTERACT4 randomized trial suggest intensive BP-lowering can lessen bleeding in the brain and improve outcomes among patients with hemorrhagic stroke—the ability to identify intracranial hemorrhage (ICH) might facilitate this strategy, said Kalra. The knowledge also could inspire EMS to pursue anticoagulant reversal in patients on the medications.

The ability to rule out ICH could, on the other hand, allow for early initiation of therapies aimed at ischemic stroke, she added.

Negative Predictive Value of 100%

Kalra and colleagues excluded patients who’d had a brain tumor or experienced stroke or traumatic brain injury within the past 3 months, since these conditions are known to elevate GFAP. They enrolled 353 acute stroke patients (mean age 74.6) admitted within 6 hours of symptom onset, using the i-STAT Alinity device to analyze blood samples collected by EMS in the ambulance before hospital arrival.

Median GFAP concentrations in patients later diagnosed with ICH were nearly sevenfold higher (208 pg/mL) than in those deemed to have ischemic stroke (30 pg/mL) and more than fourfold higher than in patients found to have stroke mimics (48 pg/mL; P < 0.001). Additionally, patients whose ICH was associated with anticoagulation had higher GFAP levels than those not on anticoagulation.

The researchers identified various cut points for diagnosing ICH across three age groups: 57 pg/mL in those younger than 72 years, 161 pg/mL in those aged 72-83, and 150 pg/mL in those older than 83. Use of these thresholds resulted in positive predictive values ranging from 90.0 to 95.5%. For patients with moderate to severe neurological deficit (NIHSS > 6), GFAP values below 30 pg/mL were able to rule out ICH with a negative predictive value of 100%.

“I actually found these results incredibly interesting and pretty surprising,” said Louise D. McCullough, MD, PhD (Memorial Hermann Hospital-Texas Medical Center, Houston), in a video interview released by the American Heart Association. The finding that a point-of-care test could differentiate between ischemic and hemorrhagic stroke “is very important because the treatment for these two diseases is very different,” she commented, noting that this knowledge could also help with transfer decisions.

“However, the study had a relatively small sample size, and for the test to be effective, both the patient’s blood and the GFAP test must be available as a ‘point-of-care’ test in the field,” McCullough noted in a press release. “Currently, most ambulances and emergency medical services do not have access to this blood test.”