C. C. McCoy1, E. Benrashid1, M. L. Shapiro1, S. N. Vaslef1, J. H. Lawson1 1Duke University Medical Center,Department Of Surgery,Durham, NC, USA
Introduction:
Current translational research in traumatic coagulopathy is limited by the heterogeneity of individual injuries and the acute, unpredictable nature of trauma incidence. As a result, coagulation studies of plasma from trauma patients lack baseline comparisons and are biased by numerous clinical factors including multisystem trauma, pre-hospital resuscitation and blood component administration. Developing both animal and human models of trauma will permit a more rigorous characterization of coagulation changes resulting from specific organ injury.
Methods:
A mouse model of blunt traumatic brain injury (TBI) was utilized to create a pilot study of TBI-specific coagulation changes. Three mice received piston-based, blunt TBI (6.8 m/s, 3mm deflection) following anesthesia and scalp retraction, while three mice received anesthesia and scalp retraction alone. Thirty minutes following intervention, blood was obtained and a proteomic analysis of coagulation was performed. 2-dimensional difference gel electrophoresis (DIGE) was coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify proteins with altered concentration in an unbiased fashion.
Results:
Multiple coagulation-related proteins were detected by DIGE, and three known coagulation proteins demonstrated concentration alterations (greater than 5% concentration change) following trauma. Five novel proteins of unknown function also demonstrated alterations in concentration. Although previously uncharacterized, these proteins could serve as targets for future investigation of injury-induced changes in the plasma proteome.
Conclusion:
Detecting concentration changes of known coagulation factors and novel proteins during TBI reinforces the value of organ-specific models of trauma as a mechanism to study the plasma proteome during injury. To validate animal model findings, proteomic analyses will be performed on human plasma collected before, during and after elective surgery to develop human, organ-specific injury models. Data from such research will enhance our knowledge of coagulation changes during tissue trauma, the influence of inflammatory pathways, and their relationship to organ-specific injury.
