Comparison of the Source and Prognostic Utility of cfDNA in Trauma and Sepsis
CCCF ePoster library. Jackson Chornenki N. Nov 9, 2018; 233330
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Nicholas Jackson Chornenki
Nicholas Jackson Chornenki
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Abstract
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Introduction: Traumatic injuries are a major cause of morbidity and mortality worldwide. In trauma patients, cell and tissue death can result from inflammation or injury. Cell-free DNA (cfDNA) has anti-fibrinolytic and pro-coagulant effects and can be released by neutrophils via NETosis in response to infection, sterile inflammation, and hypoxia or by processes like necrosis. Previously, cfDNA has been noted to be elevated and prognostic in sepsis. In patients with severe traumatic brain injury, high levels of cfDNA were associated with an increased risk of death. Protein C (PC) is a natural anticoagulant that inhibits coagulation in the microcirculation. Low PC levels are associated with increased risk of death in sepsis.



Objective: to determine if cfDNA or PC, previously shown to be capable of discriminating between survivors and non-survivors in sepsis, had prognostic utility in trauma patients.

 

Methods: Patient plasma samples were obtained from a combination of two prospective observational cohort studies: DYNAMICS (NCT0135504) and ENPOLY.  Clinical data and plasma samples were obtained on admission, daily for the first week, and then weekly thereafter. Levels of cfDNA, PC, and Myeloperoxidase (MPO) were measured in the plasma using established laboratory protocols.  Using 293XL-hTLR9 reporter cells, we determined the levels of NF-kB activation by these cells in response to cfDNA from the ENPOLY samples at all time points.

 

Results: A total of 77 trauma patients were included (n=38 from DYNAMICS and n=39 from ENPOLY). The median age was 49 yrs; 27.3% were female. Mortality was 16.9% at 28 days. Levels of cfDNA were elevated compared to healthy values in our patient population, but not significantly different between survivors and non- survivors. PC levels were reduced in our population compared to normal levels but did not differ significantly between survivors and non-survivors.  Platelet count on admission was significantly lower in non-survivors than survivors (p< 0.01) suggesting an underlying consumptive process. Receiver Operating Characteristic curves for predicting mortality are shown in Table 1. When plasma samples were added with 293XL-hTLR9 reporter cells, there was no production of SEAP at any time point, indicating no NF-kB activation and the cfDNA in trauma samples is not bacterial in origin. When MPO levels were quantified as a surrogate marker of NETosis, there was no correlation to cfDNA levels (r= –0.192, p = 0.115); however, a positive correlation existed between MPO and cfDNA in a comparison group of septic patients (n=52) from the DYNAMICS study (r=0.424, p < 0.001).

 

Conclusion: Levels of cfDNA and PC are abnormal in multiple critical conditions such as sepsis and trauma. However, variation in the source of cfDNA between septic and trauma patients may account for differences in prognostic utility. In trauma patients, future studies into dysregulation of platelet production and function may prove useful for improving survival.

 

 

 

 


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