Leading a Breakthrough

How Orlando Health shepherded a rapid blood test expected to change the game for concussion care

It isn’t often in healthcare that a person gets to be part of a major step forward in medicine. But that’s exactly what’s happening in the emergency department at Orlando Health. The same clinical team that responded to the horrifying Pulse nightclub mass shooting in 2016 is now on the cusp of an important advancement that will vastly improve how concussions are managed.

In the 1990s, Linda Papa, M.D., was starting her medical career as a young resident in emergency medicine. At the time, guidelines for traumatic brain injuries (TBIs), including mild TBIs (also known as concussions), were just starting to emerge. “Management of TBI, particularly, mild TBI, was somewhat of a black box. There was a need for more research to help physicians manage and diagnose them,” says Dr. Papa, who is the Director of Clinical Research at Orlando Health.

At the time, the CT scan as a diagnostic tool for TBI was only a few decades old, and clinicians were still getting used to the relatively new technology. “There were no guidelines for when to use them on patients with mild TBI,” shares Dr. Papa, “So we would do scans on the patients we thought needed them.” Sometimes this meant CT scans were done on those who didn’t need them, while other patients actually had important injuries that were missed.

Dr. Papa also noticed that some patients with mild TBI or concussion who had normal CT scans and were discharged would return to the emergency departments—days or weeks later—with persistent post-concussive symptoms such as headaches, problems concentrating, memory loss, insomnia, anxiety and balance problems. A CT scan would be repeated and was usually negative. Patients and their families were frustrated, and in some cases devastated, because there was no objective evidence to explain the brain injury symptoms.

Unraveling a mystery

Since then, clinical guidelines have evolved to allow physicians to make more informed decisions about when a CT scan should be performed. But it hasn’t solved the problem. There are still too many scans being performed, unnecessarily exposing patients to radiation and increasing healthcare costs. Also, CT scans do not diagnose concussion. In fact, most patients with concussion have a normal CT scan.

Dr. Papa knew there had to be a better way and sought to find answers. She focused on the fact that there was no blood test for the brain like there was for other organs such as the heart, liver and kidneys. This testing obstacle was because the brain is protected by the blood-brain barrier, which acts as a gatekeeper, preventing certain kinds of substances from going in and out of the brain. Inspired by her patients, Dr. Papa dedicated her career to researching a better way to diagnose people with suspected TBIs.

At the turn of the millennium, Dr. Papa started working with neuroscientists to systematically identify substances that show up in a rat’s brain after an injury. The team then looked for these substances, known as biomarkers, in the fluid around the brains of people with severe TBI. “After a severe brain injury, there is bleeding and swelling of the brain, so cerebrospinal fluid is removed using a special drain to decompress the brain,” says Dr. Papa. “Rather than discarding the fluid, as usual, we examined the fluid for the most promising biomarkers.”

In 2005, Dr. Papa conducted the first groundbreaking biomarker study in patients with mild TBI in the emergency department using the protein biomarkers GFAP and UCH-L1. As a result, the team was finally able to detect them in the blood of patients with mild TBI and concussion. “I was analyzing the data one night and was so excited when I saw how well the amount of biomarker in the blood correlated with the severity of the brain injury, even in the mildest of injuries. It was a eureka moment!”

This became the blood test for TBI.

Dr. Papa and the team started presenting at conferences and publishing in medical journals, and the findings garnered considerable attention, particularly from the U.S. Department of Defense (DoD) and the National Institutes of Health. The DoD and Abbott Laboratories worked to further develop and go to market with the innovative test. On April 1, 2024, the first whole-blood point-of-care test was approved by the U.S. Food and Drug Administration (FDA) for adult use. In August, Orlando Regional Medical Center became the first hospital in the world to use the new TBI blood test to assess ER patients with suspected concussion.

Improving concussion care for kids

The team is currently working to get the TBI blood test FDA-approved for children. “This will be an important test for children because they can’t always verbalize what happened or how they feel, and it’s crucial to know how severe their brain injuries are,” says Dr. Papa.

Of the children who are scanned for TBI, 80% to 90% come back normal. The problem is that a CT scan exposes them to potentially harmful radiation. The younger a person is exposed to radiation, the higher their risk for developing cancer. “The health risks and benefits are different for children, but we have to do scans because we do not want to miss critical injuries,” says Dr. Papa. A TBI blood test could significantly reduce the number of unnecessary CT scans for both children and adults alike.

How it works

A nurse or other healthcare professional takes blood from the patient with a suspected TBI and places a few drops into a custom-made handheld medical device, which detects two proteins in the blood called GFAP and UCH-L1 in as little as 15 minutes. These biomarkers are released from brain cells when they are damaged. If these protein concentrations are below a certain threshold, a CT scan can be avoided. Alternatively, if either protein is above the threshold, a CT scan should be performed. The higher the concentrations

of the biomarkers, the more severe the TBI.

“Often, emergency physicians feel a CT is not warranted, but are uncomfortable making that decision, so many CT scans are ordered unnecessarily,” says Dr. Papa. “Now, we have an objective blood test to corroborate our clinical decisions. More importantly, if protein levels are unexpectedly high, it alerts us to the severity of brain injury and allows us to get patients the critical care they need right away.”

The first FDA-approved test in 2018 took four hours to produce a result. Eventually, scientists at Abbott were able to bring it down to 15 minutes. “We don’t need bulky machines, and we don’t have to process the blood anymore,” says Dr. Papa. “Now it’s a point-of-care test in the emergency department at the patient’s bedside.”

The rollout at Orlando Health has been thrilling. Clinical staff are excited that they can see patients’ TBI biomarker levels within 15 minutes and it’s improving patient care. “It is so rewarding to see a dream that started 25 years ago actually come to the bedside and improve the way patients are cared for,” says Dr. Papa.

Making the leap from discovery to standard practice

When Jennel Lengle, VP of Supply Chain Board and Clinical Operations at HealthTrust, heard about Orlando Health’s TBI blood test implementation, she got excited about the prospect of getting the device on contract and into member organizations’ emergency departments across the country. “I recognized that it was leading practice and took it to our Laboratory Clinical Advisory Board for discussion,” says Lengle.

After the TBI blood testing device was approved by the FDA, it was presented to HealthTrust’s Laboratory Advisory Board. “Every category we contract for within the healthcare space has been evaluated by subject matter experts in the field. Our Lab Advisory Board is made up of experts in the lab space who represent member organizations,” says Lengle.

The board approved the product to be brought on contract at the group purchasing organization (GPO). Members can now purchase this device and test (Contract #500273) on contracted pricing in the point-of-care testing category and incorporate it into care processes at their organizations.

The future is bright

Currently, the test is only approved to guide decision-making on whether or not an adult patient with suspected mild TBI should have a CT scan within 24 hours of injury. Eventually, the hope is for the test to become the standard of care for TBI.

After spending 25 years helping to bring the TBI blood test to fruition, Dr. Papa envisions a future brimming with possibility, including using the test to diagnose a concussion, to predict recovery, as well as to discover and monitor new treatments for TBI that have been elusive to date.

In one of her most recent studies, Dr. Papa showed that the TBI blood test could be used as early as within 30 minutes after injury. This opens up the possibility of using the test in pre-hospital settings, for example, along the sidelines of organized sports or within the military to assess personnel on active duty. There might also be application for primary care settings as well as rural or underserved communities where CT scans aren’t available. “In a way, we’re just getting started,” says Dr. Papa. “I can’t wait to see what the future holds.”