The more time that elapses before a stroke is diagnosed and treated, the more brain tissue is irreparably damaged, and the worse the outcome for the individual. However, even when symptoms point to a stroke, it is crucial to distinguish between a hemorrhagic (bleeding) or ischemic (clot-caused) stroke before giving treatment. That’s usually done through imaging, which can be delayed for hours while a patient is stabilized, brought to the emergency room and then on to radiology for a brain scan — all the while brain cells are dying.

“It is crucial to differentiate these two types of stroke because they need opposite treatments. In ischemic stroke, you need to open the blocked blood vessel with clot-busting drugs or physically remove the clot. In contrast, in a bleeding stroke, you need to lower increased blood pressure and give medication to reverse the effects of certain blood-thinning drugs,” said lead study author Love-Preet Kalra, M.D., a neurology resident at the RKH Hospital Klinikum Ludwigsburg, in Germany.

Researchers studied whether blood levels of glial fibrillary acidic protein (GFAP) could be useful for quickly diagnosing stroke types. GFAP is a protein specific to the brain released into the bloodstream when brain cells are damaged or destroyed. It is already used in assessing traumatic brain injuries.

In a parallel study published in 2024, Kalra and colleagues found that GFAP levels could rapidly distinguish who had a bleeding stroke among unresponsive patients. In this study, researchers evaluated whether levels of GFAP could differentiate between hemorrhagic stroke (caused by bleeding) and ischemic stroke (caused by a blood clot), as well as conditions that mimic a stroke. This assessment was conducted using blood samples collected by the emergency medical services ambulance team before patients arrived at the hospital.

The analysis found that GFAP levels were:

• almost 7 times higher in patients with bleeding stroke than those with clot-caused stroke (208 picograms per milliliter, or pg/mL, vs. 30 pg/mL);
• more than 4 times higher in patients with bleeding stroke than those with stroke mimics (208 pg/mL vs. 48 pg/mL);
• able to rule out bleeding stroke when below 30 pg/mL in patients with moderate to severe neurological deficits;
• able to predict which patients had a bleeding stroke with 90%-95% accuracy when age-based cut-off points were used. These age-based groups were evenly distributed: below age 72, between age 72 and 83, and above age 83. Notably, the cut-off for the below 72 was very low.
• higher in bleeding stroke patients taking blood thinners than those not on blood-thinning medications.

“I was personally surprised by the extremely elevated GFAP values in blood thinner-associated bleeding stroke and the fact that, in moderately or severely affected acute stroke patients, bleeding stroke could be excluded in all cases which showed a GFAP lower than 30 pg/mL,” Kalra said.

If larger studies confirm the results, Kalra said early GFAP measurements could change how people with stroke symptoms are treated.

“Treatment to lower blood pressure and reverse blood-thinning medications could be performed in the prehospital setting, leading to a huge change in clinical practice. In the future, even blood thinners or clot-busting treatment might be applied before people reach the hospital,” Kalra said.

A limitation of this test is that a centrifugation step (separates the components of blood) is currently needed. GFAP also increases with age, creating a grey area in which small bleeding strokes might not be identified or mistaken for ischemic strokes in elderly patients.

“This study reveals that levels of GFAP, a marker for brain injury, are higher in patients with brain hemorrhages compared to those who have strokes caused by blood clots. This finding suggests that GFAP could serve as a useful prehospital test for assessing brain injuries. 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. Currently, most ambulances and emergency medical services do not have access to this blood test,” said American Heart Association expert volunteer Louise D. McCullough, M.D., P.H.D., FAHA, who is the Roy M. and Phyllis Gough Huffington Distinguished Chair of Neurology at McGovern Medical School; chief of neurology at Memorial Hermann Hospital-Texas Medical Center and co-director of UTHealth Neurosciences, all in Houston. McCullough was not involved in this study.

Study details, background or design:

• The study included 353 people (average age 75, 47% women) reaching the emergency room within six hours of the onset of stroke symptoms.
• People were excluded from the analysis if they had previously had a brain tumor or if they had experienced a stroke or traumatic brain injury within the past three months.
• Blood was drawn before they reached the emergency room at RKH Hospital Ludwigsburg in Ludwigsburg, Germany, where the blood was tested for GFAP levels using a portable blood analyzer.
• Brain imaging diagnosed intracerebral hemorrhage (bleeding stroke) in 76 people, clot-caused strokes in 258 and conditions mimicking stroke (such as seizure or migraine), in 19 people.
• GFAP levels were compared between groups based on the diagnosis at hospital discharge.