WP lead: Dr. Sisse Rye Ostrowski, Copenhagen
To improve our understanding of the body’s acute response to injury TACTIC will determine patterns of different TIC biomarkers to:
- Identify biomarker signatures associated with haemorrhagic coagulopathy (measurement of coagulation factors, natural anticoagulants and fibriniolysis markers in plasma samples from trauma patients).
- Identify biomarker signatures associated with vasculopathic coagulopathy (measurement of biomarkers of sympathoadrenal activation and endothelial cell activation and damage in plasma samples from trauma patients).
The combined output of the haemorrhagic and vasculopathic coagulopathy biomarkers will be used in WP5 to enable the molecular description of different coagulopathic patients in relation to their functional coagulation status. Furthermore, the correlation of biomarkers with outcomes (e.g. patterns of organ dysfunction, infection) will be investigated.
TIC is heterogeneous in nature and the influence of genetic background is yet unknown. Here TACTIC will target genetic elements associated with vasculopathic coagulopathy to identify determinants that confer the adverse acute pathology (e.g. early TIC) and adverse patient outcome by:
Identify genetic polymorphisms that predispose patients to TIC & adverse outcomes (measurement of SNPs for α and β adrenergic receptor, thrombomodulin receptor, protein C system, syndecan-1, Angiopoietin 2, HMGB1 and TLR2 systems in DNA from trauma patients).
The SNPs identified to be significantly associated with early TIC or more adverse outcome will be prospectively evaluated for their predictive value. Further analysis of samples collected during the TACTIC RCT will be conducted to enable the refinement and testing of hypotheses as appropriate (Year 5). These results will provide substrate for further efforts to deliver novel diagnostic assays for the earlier and more accurate identification of patients at risk of TIC and developing more adverse outcomes.