Characterizing the impact of traumatic brain injury phenotype on coagulation dynamics in severely injured patients

In severely injured patients, altered coagulation impairs stable clot formation and increases mortality. Traumatic brain injury (TBI) precipitates alterations in clot formation and breakdown. In this study, we aimed to characterize clotting kinetics, mechanics, fibrin networks, and circulating proteomic markers in TBI patients, and correlate these biomarkers to outcomes.

Plasma samples were collected from 63 injured patients upon presentation. Clotting kinetics, structure, fibrinolytic markers, thrombin generation, and proteomic profiles were analyzed. Clinical chart review was performed using our institution's trauma registry and medical records.

We analyzed coagulation and clinical factors of 34 No-TBI, 29 TBI patients and 7 healthy donors. Demographics were comparable between patient groups. TBI patients had increased mortality and larger perturbations in coagulation mainly in intrinsic coagulation and fibrinolytic function. Upon admission, TBI patients had higher D-dimer, lower factor VIII, and lower von Willebrand factor than No-TBI patients. TBI patients had reduced coagulation factor XIII alpha chain than healthy donors. Subgroup analyses included isolated TBI, polytrauma with TBI, and varying TBI severities. We identified distinct contributions of intracranial and extracranial injury on coagulopathy, thrombin generation and coagulation factor concentrations. Along with this, Severe TBI was associated with increased prehospital fibrinolysis, without an increase in tissue plasminogen activator concentration or fibrinolysis at blood draw.

TBI patients demonstrated patterns consistent with prehospital fibrinogen consumption and fibrinolysis. Unique differences were observed between the phenotypes of TBI, with severe isolated TBI patients exhibiting lower levels of vWF, Coagulation Factor VIII, Coagulation Factor XIII alpha chain, and PAI-1. These findings highlight the temporal and injury-phenotype contributions to TBI-induced coagulopathy.