Plasma levels of von Willebrand factor may be a useful biomarker traumatic brain injury (TBI) and its severity, suggest new research.
“Reliable detection of this biomarker at very early times can allow for rapid detection of TBI and therefore intervention,” Rachel Elizabeth Thomas, MD, PhD, a resident neurologist at the University, told study researchers of Pennsylvania, Philadelphia, Pennsylvania. Annual Meeting of the American Academy of Neurology (AAN) 2021.
“The level reflects the degree of severity and provides a certain degree of prognostic information,” he added.
A specific marker of acute injuries?
Von Willebrand factor is a glycoprotein released into the endothelium in response to local trauma. It plays a role in hemostasis and inflammation and is an indicator of traumatic microvascular injury. Research has shown that it is a biomarker of cerebrovascular pathology. In addition, increased factor expression is associated with vascular and neurodegenerative dementia.
The researchers examined whether von Willebrand factor is a mild and repetitive biomarker of TBI. They measured plasma levels of von Willebrand factor in 17 professional boxers before and after boxing fights.
Eligible participants were between 18 and 35 years old. They had a score of ≥1 on the Rivermead Postcussion Symptom Questionnaire (RPQ-3), had competed in at least three 3-minute fights, and had resisted 25 or more blows to the head.
The researchers compared the plasma levels of von Willebrand factor in boxers with those of 42 patients presented at the University of Pennsylvania Trauma Center with TBI and those of 23 people monitored without injuries.
There were no significant differences in von Willebrand factor plasma levels between pre-fight boxers (13.15 µg / mL) and control individuals (6.16 µg / mL). Among boxers, von Willebrand factor levels increased by a factor of 1.8 in 30 minutes after fights, compared to levels among controllers. The mean von Willebrand factor level after combat was 25.09 µg / mL.
“The Von Willebrand factor may be more specific for acute injuries, as it does not appear to remain chronically elevated,” Thomas said.
In addition, the researchers found a significant positive correlation (r = 0.51; Pg = 0.03) between the change in folding in von Willebrand plasma factor levels and the number of blows to the head suffered by athletes.
They also found a significant positive correlation between the change in folding in the von Willebrand factor and the RPQ-3 score (r = 0.69; Pg = .002). These objective and subjective data suggest that von Willebrand factor levels reflect the severity of the injury, Thomas said.
Among hospitalized patients with TBI, von Willebrand factor levels were significantly higher than those of control individuals (73.2 µg / mL vs. 40.8 µg / mL; Pg <.0009). The researchers found a linear correlation between von Willebrand plasma factor level and RPQ-3 score (r = 0.24) which was not statistically significant.
Von Willebrand factor levels among hospitalized patients with TBI were on average higher and showed a greater degree of variability than levels among boxers immediately after a fight.
“This is not unexpected, as this group represents a more heterogeneous population with various forms of acute blunt injury, compared to boxers, who have suffered relatively repetitive and milder trauma,” Thomas said. Medscape Medical News.
Traditional neurotrauma biomarkers reflect neuronal and glial lesions, while von Willebrand factor is an indicator of vascular trauma.
“Although alone, von Willebrand factor is not specific to intracranial vascular injury, combined with markers such as neurofilament lumen, GFAP [glial fibrillary acidic protein], and tau, could be used to identify TBI-associated microvascular lesions and thus delineate between TBI-specific endophenotypes, “Thomas said. It could distinguish, for example, predominant neuronal lesions from predominantly vascular lesions.
Because von Willebrand factor plays a role in the neurovascular unit and is a marker of microvascular injury, the researchers aim to pair plasma von Willebrand factor measurements with advanced imaging techniques to assess cerebral blood flow or cerebrovascular reactivity. This study could help determine whether von Willebrand factor levels correlate with the degree of vascular injury and cerebrovascular dysregulation.
Point of care test?
Commenting on the findings of Medscape Medical News, Kristine O’Phelan, MD, professor of clinical neurology and director of neurocritical care in the Department of Neurology at Miller University School of Medicine, Coral Gables, Florida, said the likely utility of the Von Willebrand factor would be as a marker of injury in patients with mild or sport-related TBI concussion.
Imaging and clinical examinations do not always reveal these lesions, O’Phelan added. “Having a biomarker that can be easily tested in the blood would be very helpful,” he said.
The most exciting part of this study is that it indicates the potential to develop a point-of-care test for use on the athletic field or on the battlefield for the early detection of mild TBI, he added.
The fact that the von Willebrand factor test has already been developed is an advantage, O’Phelan said. The normal and abnormal values of the test are clearly understood. “I think they will still have to calibrate it for head wound, because the test is not usually used, “O’Phelan said.
One of the strengths of the study is that the researchers compared patients with TBI to monitor people who had exercised, he added, because that comparison helps clarify the relationship of the biomarker to the injury. Another strong point is the application of the test to injuries of various types and degrees of severity.
But the biomarker will have to be tested in a larger population, O’Phelan said. In addition, it is necessary to identify the appropriate patient population for this test, as well as the best time period for its application and possible factors that could confuse the test results.
“I’m a little concerned about the use of early biomarkers for prognosis, especially in severe TBI, because there are a lot of variables that go into the outcome,” O’Phelan said. This test would probably be administered in the first hours after the injury, but many factors can affect patient outcomes, he added.
An influential factor is age. “If you have a von Willebrand factor of any number, this could be of a different importance in a 30-year-old than in an 80-year-old,” O’Phelan said. “We need to understand how to better interpret these findings.”
The study was supported by the National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense and the Pennsylvania Department of Health. Thomas and O’Phelan have not disclosed any relevant financial relationship.
Annual Meeting of the American Academy of Neurology (AAN) 2021: Summary S26.005. Filed April 21, 2021.