Traumatic brain injury (TBI) has a tremendous impact on global morbidity and mortality and there has been great interest in using biomarkers to diagnose TBI early and accurately for better disease management.¹ To achieve clinically meaningful diagnosis, Dr. Rachel traumatic, a neurology resident at the University of Pennsylvania, United States, considered the selected biomarkers should ideally have (1) high sensitivity/specificity for early detection, (2) strong correlation with the severity of injury and (3) significant predictive value for patient outcomes.

von Willebrand Factor is a large glycoprotein that is released from the endothelium during local trauma.² In the traumatic setting, von Willebrand Factor contributes to both thrombosis and inflammation and is an attractive candidate biomarker for identifying traumatic microvascular injury.³ To investigate its role in repetitive mild TBI, Dr. Thomas and investigators conducted a study which measured the plasma levels of von Willebrand Factor among professional boxers before and after boxing bouts.

Eligible patients consisted of professional boxers aged 18 to 35 (n=21) who had competed in at least three 3-minute bouts. The controls were non-injured, exercise subjects. Blood samples were collected from the athletes pre- and post-bout. Within-bout, the number of head blows were assessed by three independent examiners. The Rivermead Post- Concussion Symptoms Questionnaire (RPQ-3) assessment was then performed post-bout to assess the symptom severity.

Non-statistically significant differences were observed between von Willebrand Factor levels in the control and boxers pre-bout (baseline) (p<0.62). However, at 30 minutes post-bout, a significant increase in plasma von Willebrand Factor was observed when compared to the baseline level (p<0.000001). Dr. Thomas further commented that, “von Willebrand factor may be more specific for acute injuries given that it does not seem to stay chronically elevated.”

Investigators also found that fold-change in plasma von Willebrand Factor levels were moderately correlated with the number of blows to the head at 30 minutes post-bout (r=0.51; p=0.03) with 48 being the average number of blows. Moreover, a positive correlation between fold-changes in plasma von Willebrand Factor and RPQ-3 scoring was demonstrated (r=0.69; p=0.002).

Outside of the professional boxers, patients who were hospitalized with TBI due to acute blunt trauma including falls, assault and motor vehicle collisions had a significant increase in plasma von Willebrand Factor levels following TBI when compared to uninjured patients (p<0.0009).² A positive correlation between levels of plasma von Willebrand Factor and RPQ-3 scoring was also found but was not statistically significant (r=0.24; p=0.1788).

Dr. Thomas thereby concluded that, “The data demonstrates that von Willebrand Factor may be a useful biomarker for microvascular injury in individuals who suffered TBI, both secondary to mild repetitive trauma as well as acute, blunt trauma.” Based on the study results, reliable detection of this biomarker at very early time-points may allow prompt TBI identification and therefore intervention. Furthermore, the level of von Willebrand Factor may reflect the degree of severity and provides prognostic information. In the point-of-care setting, Dr. Thomas further suggested that the study data may also offer the potential utility on the sports field, battlefield or ambulance/ emergency department.

In the future, more advanced imaging techniques such as cerebral blood flow analysis can be used to determine the correlation between von Willebrand Factor level and the degree of vascular injury and cerebrovascular dysregulation. TBI endophenotypes may also be distinguished through von Willebrand Factor to determine whether the injury was predominantly vascular or neuronal.