Blood Test Could Improve Diagnosis of Severe Strokes on a Global Scale

By Deborah Borfitz 

June 4, 2024 | A potentially game-changing diagnostic assay is under development that can quickly and accurately identify who is and isn’t having a large vessel occlusion (LVO), a devastating subset of ischemic stroke that occurs when a major artery in the brain is blocked. The portable fingerprick blood test combines two biomarkers with a simple scale used by paramedics to calculate stroke severity to “rule in ischemic clot and rule out brain bleeds,” according to Joshua Bernstock, M.D., Ph.D., a clinical fellow in the department of neurosurgery at Brigham and Women’s Hospital and medical director of UK-based Pockit Diagnostics. 

Head bleeds could not be differentiated from LVO in the field up until now, he says. The new detection tool showed an impressive 93% specificity for the highly aggressive stroke in a TIME (Testing for Identification Markers of Stroke) trial that published recently in Stroke: Vascular and Interventional Neurology (DOI: 10.1161/SVIN.123.001304).  

This suggests that patients who test LVO-positive should be transported directly to a comprehensive stroke center, bypassing local community hospitals lacking the ability to perform an endovascular thrombectomy to mechanically retrieve and aspirate the clot, says Bernstock. The critical task at this point, even in high-income countries like the U.S. and U.K., is “is getting patients to the right place at the right time.” 

Intravenous tissue plasminogen activator (tPA) has been the standard treatment for ischemic strokes since the 1990s, but it is much less effective for strokes caused by LVO, he says. In 2015, a landmark series of clinical trials were published showing the efficacy of endovascular thrombectomy over tPA in patients experiencing LVO strokes. Although the window of surgical opportunity was initially thought to be within six hours of symptom onset, it has since been well demonstrated that there are benefits for up to 24 hours “so it is really about ending at the right place as soon as possible.”  

The biomarkers in the test are glial fibrillary acidic protein (GFAP), also associated with brain bleeds and traumatic brain injury, and D-dimer, the protein produced when a blood clot dissolves. “GFAP is already FDA-approved for TBI [traumatic brain injury], but nobody before us has been able to put it in a lateral flow format… [suitable for] pre-hospital settings,” says Bernstock.  

Economic Value 

LVO ischemic stroke is a blockage of proximate flow vessels that deprives large areas of the brain of vital nutrients and oxygen, Bernstock explains. They continue to be lethal, and lead to severe morbidities, largely because patients are not getting properly diagnosed. 

The global macroeconomic consequences related to stroke are also vast, as Bernstock and his colleagues reported last year (Stroke, DOI: 10.1161/STROKEAHA.123.043131). The “value of lost welfare” was pegged at 1.66% of the global GDP. The largest share was attributed to the ischemic stroke subtype, where LVO accounts for about one-third of cases. 

“In stroke care, time is brain,” Bernstock says. “The faster we can get these people to appropriate care the better.” For many LVO stroke patients today, the odyssey begins with imaging at an emergency department in a local hospital where a brain scan is done and, if the diagnosis is confirmed, they are transferred to a specialist regional hospital for treatment.  

Delays are associated with a risk of complications, including hemorrhagic transformation whereby removal of the blockage can result in a massive brain bleed. But even then, the benefits of having the procedure have been shown time and again to outweigh the risks, says Bernstock. 

For patients whose LVO stroke is detected in a timely fashion, endovascular thrombectomy has proven to be “absolutely transformative,” he notes. “With the right team and right intervention, they can walk out of the hospital days later like it never even happened.” 

U.K. Trial Begins

One imagined utility of the test will ultimately be to rule out brain bleeds in the ambulance so intravenous tPA can be started on those patients as they are being moved to a higher echelon of care, says Bernstock. Those determined to have brain bleeds might also be triaged and sent to either a primary stroke center for medical management or a comprehensive stroke center for surgical evaluation, depending on the size of the bleed. 

In terms of clinical trials underway and on the immediate horizon, the emphasis is on making a differential diagnosis of LVO in the field. The first study now enrolling participants in the U.K. is assessing how well the new blood test works so that in the future it might be routinely used in ambulances. 

Results of the new test will be compared with routine tests done following emergency arrival at a hospital, and four institutions—Royal Victoria Infirmary, Northumbria Specialist Emergency Care Hospital, University Hospital of North Durham, and Royal Blackburn Hospital—are serving as study sites. “The initial signals are very positive,” says Bernstock, adding that the goal is regulatory approval in the U.K. and Europe as well as the United States.  

The research is being undertaken by Pockit Diagnostics, founded in 2017. The principles met at the University of Cambridge, where Bernstock did his Ph.D.   

Worldwide Impact

Utility of the test in the pre-hospital space is the focus of clinical trials that will be run in the U.K. with support from the National Health Service and the U.K.-based Stroke Association, he says, with trials to start in the U.S. in the coming months. The vision is for people diagnosed with likely LVO stroke to be taken directly to a regional hospital, saving time and reducing delays before treatment.  

The trials will all look a bit different, including one leveraging the test to expedite triage of stroke patients by having them bypass standard imaging and move directly to intervention. The diagnostic technology will be leveraged in multiple ways “because we think it is so disruptive,” Bernstock says. 

The blood test could be particularly impactful in low- and middle-income countries (LMICs) where it has been problematic to get LVO stroke patients to treatment, adds Bernstock. As was shown in research published by the global network Mission Thrombectomy last year in Circulation (DOI: 10.1161/CIRCULATIONAHA.122.063366), access to mechanical thrombectomy is extremely low with enormous disparities between countries based on income level. Pre-hospital diagnostics and LVO triage policy were identified as the main drivers of this phenomenon, he points out. 

Interventionalists in 67 countries responded to the survey, which found that in countries like India and Thailand only about 1% of LVOs are being treated. Even in the U.S., which is better equipped than anywhere else in the world, the rate still sits at around a dismal 30%, says Bernstock.