PB0766 - Decreased compactness and increased fluid permeability of ex-vivo fibrin clots in patients after traumatic brain injury

Background: Traumatic brain injury (TBI) contributes to death and disability with an estimated 69 million people worldwide suffering TBI yearly. TBI increases the risk for psychopathology and cognitive decline as well as neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Fibrinogen and fibrin deposition leading to microglia and astrocytes-driven neuroinflammation in the brain tissue has been implicated in cognitive decline after TBI. It is unknown if aberrations in fibrin clot characteristics (FCC), including fibrin clot function and structure, alter the seepage of plasma fibrinogen/fibrin through the blood-brain barrier and their deposition, contributing to neurodegeneration after TBI.

Aims: To determine FCC changes in patients after TBI.

Methods: In an observational cohort of patients after TBI, we evaluated FCC in plasma samples using turbidity assay, submicron beads flow-through assay, and confocal fluorescence microscopy. Then, we compared FCC parameters among patients after TBI and matched controls.

Results: We compared FCC among 8 patients after TBI and 6 matched controls. Our results suggest no difference in fibrin clot formation and lysis kinetics on turbidity assay. However, fibrin clots of patients with TBI had a faster saline transit rate (mean+/-SD saline transit time of 24 min+/-22, n=8) compared to matched controls (91 min+/-75, n=6, p-value =0.03, unpaired t-test) (figure 1). Notably, ex-vivo fibrin clots of patients with TBI had decreased fibrin fibers density (mean+/-SD background non-fluorescent area of 50.5+/- 25.7, n=8) compared to matched controls (11.5+/-3.5, n=6, p-value=0.007, unpaired t-test) (figure 2).

Conclusion(s): Distinct FCC alterations may exist in patients after TBI, including decreased compactness and increased fluid permeability. In the future, we plan to evaluate if FCC changes are associated with deficits in neuropsychological performance in patients after TBI.