Role of early cell-free DNA levels decrease as a predictive marker of fatal outcome after severe traumatic brain injury

Abstract

Introduction: Circulating cell-free DNA levels are increased after trauma injury. This increase is higher since the first hours after trauma and may be related with primary outcome. A sensitive and reliable biomarker for patients at higher risk is needed to identify these patients to initiate early intervention. In this way, circulating DNA may be a possible biological marker after severe TBI.

Materials and methods: We investigated DNA plasma concentrations after severe traumatic brain injury and during the next 96 h in the Intensive Care Unit (ICU) by real time PCR. 65 patients suffering severe TBI were included in the study.

Results: Cell-free DNA levels were considerably higher in patients samples compared with voluntary control ones. After the following four days we observed a 51% decrease during the first 24h and a 71% fall from 48 h. TBI population was stratified for the primary outcome (survivors/non-survivor) and DNA levels decrease ratio was calculated for the first 48 h. A higher decrease in the survivors from 0 h to 24h compared with the non-survivors was found. A cut-off point of 1.95 ratio was established for the detection of the highest proportions of patients after the TBI that will not survive after the injury with a sensitivity of 70% and specificity of 66%.

Conclusions: In summary we showed that severe TBI is associated with elevated cf-DNA levels and we propose that cf-DNA decrease during the first 24h may predict patient outcome.