TBI Blood Biomarkers Show Accuracy Within 30 Minutes of Injury

Blood biomarkers taken within an hour of injury signaled the presence of CT lesions and the need for 24-hour neurosurgical intervention with high accuracy in patients with traumatic brain injury (TBI), a cohort study found.

In an analysis of blood samples from a previous trial, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) were significantly elevated within 30 and 60 minutes of injury, Linda Papa, MDCM, MSc, of the Orlando Regional Medical Center in Florida, and colleagues reported in JAMA Network Open.

Of blood biomarkers taken within 30 minutes, GFAP had the highest diagnostic accuracy, with the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, need for neurosurgical intervention, and clinically important early outcomes (CIEO) — a composite outcome including early death, neurosurgery, and prolonged mechanical ventilation — within a week of injury:

• CT lesions: AUC 0.88, 95% CI 0.85-0.92
• Need for neurosurgical intervention: AUC 0.78, 95% CI 0.72-0.84
• CIEO: AUC 0.89, 95% CI 0.85-0.93

In blood samples taken within 60 minutes, GFAP also had the highest AUCs. Various biomarker combinations were not better than GFAP alone.

Overall, GFAP showed the strongest independent association with outcomes, with sensitivities of 98% to 99% and specificities of 18% to 36%.

“This study addresses a critical knowledge gap by using a large cohort of TBI patients enrolled in a multicenter prehospital TBI clinical trial,” Papa told MedPage Today in an email. “To our knowledge, this is among the first studies to show the performance of these biomarkers so early after injury on such a large scale.”

The findings show blood biomarkers can be used much earlier after injury than previously thought, she noted. “This opens up the possibility for using these biomarkers in many settings” like prehospital settings or in ambulances, on the sidelines of organized sports, and in the military,” she said.

The FDA cleared the first blood test for detecting GFAP and UCH-L1 in mild TBI in 2018. “However, implementation of these biomarker tests into clinical practice has been slow, in part because the currently cleared context of use is narrow,” Ramon Diaz-Arrastia, MD, PhD, of the University of Pennsylvania in Philadelphia, wrote in an accompanying editorial.

“In this study, Papa and colleagues present data that suggest another potential context of use, namely the use of these biomarkers in prehospital settings,” Diaz-Arrastia observed.

“Assaying blood biomarkers at the scene of the injury or during ambulance transport would help inform the decision of whether the patient can safely be transported to the nearest ED [emergency department], or whether the nearest ED should be bypassed because the patient is likely to need neurosurgical care that may only be accessible at a higher-level trauma center,” he added.

Very little research has addressed this context, since most studies have used blood samples collected several hours after injury, Diaz-Arrastia noted.

The study raises a few key questions, he pointed out. “The first is whether UCH-L1 measurements add value, or whether GFAP alone is sufficient,” he wrote.

“A second question is whether other biomarkers could improve on the specificity, particularly for the need for neurosurgical interventions and clinically meaningful outcomes (mortality, need for delayed neurosurgical intervention, or prolonged mechanical ventilation), for which GFAP alone at a standard cutoff has marginal specificity of around 20%.”

Researchers analyzed blood samples from the Prehospital Tranexamic Acid Use for TBI clinical trial, conducted from 2015 to 2017, that took samples from hemodynamically stable patients with suspected TBI and a prehospital Glasgow Coma Scale score of 3 to 12, indicating moderate to severe injury.

They included 804 patients who had samples drawn and biomarker data. These patients had a mean age of 41; 74.2% were male, and 71% were white. Most samples (563) were taken within 60 minutes of injury; of these, 375 were taken within 30 minutes.

Of those with samples drawn within 60 minutes, 56.1% had traumatic intracranial lesions on CT, 16.9% had neurosurgical intervention within 24 hours of injury, and 30.6% had CIEO.

All three biomarkers showed significant incremental elevation with worsening diffuse injury on CT. Each biomarker also had significant associations with individual components of CIEO, especially early mortality.

Limitations included a large proportion of male participants in the study. Researchers also did not examine specific clinical circumstances beyond needing neurosurgical care.