R. A. Namas1, X. Zhu1, D. Liu1, O. Abdul-Malak1, J. Sperry1, Y. Vodovotz1, T. Billiar1 1University Of Pittsburgh,General Surgery,Pittsburgh, PA, USA
Introduction: Trauma-induced coagulopathy (TIC) is often associated with a broad systemic inflammatory response that can predispose patients to follow a complicated clinical course. Despite significant recent advancements associating post-traumatic inflammation with TIC, a better understanding of this complex interaction is needed. To characterize the systemic inflammatory response accompanying TIC, we analyzed an extensive time course of circulating inflammatory mediators coupled with data-driven modeling.
Methods: From a cohort of 472 blunt trauma survivors, 114 patients had TIC (defined by admission INR ≥ 1.3). After excluding patients with history of anticoagulant intake pre-trauma, 98 TIC patients (71 males [M] and 27 females [F], age: 39.7 ± 2, injury severity score [ISS]: 23.7 ± 1) were matched to 98 non-TIC patients (71/27 M/F, age: 39.8 ± 2, ISS: 23.4 ± 1) for age, gender ratio, and ISS using IBM SPSS®. Three samples within the first 24 h were obtained from all patients and then daily up to day 7 post-injury and assayed for twenty four inflammation biomarkers using Luminex™. Two-way analysis of variance was used to determine statistical significance (p<0.05) between the TIC and non-TIC sub-groups. Dynamic network analysis (DyNA) was used to infer dynamic connectivity and complexity among the inflammatory mediators.
Results: ICU length of stay (LOS), total LOS, and days on ventilation were statistically significantly prolonged in the TIC group when compared to non-TIC group. In addition, the TIC group had a greater requirement of operative intervention within the first 24 h post-admission. The TIC group had a higher degree of organ dysfunction from days 1 to 7 when compared to the non-TIC group. Importantly, circulating levels of IL-6, IL-10, MCP-1, MIG, IP-10, and IL-8 and were significantly elevated in the TIC group. DyNA suggested that the inflammatory response in the non-TIC group had a higher coordinated degree of interconnectivity while the response in TIC consisted of multiple sparse nodes with reduced interconnectivity within the initial 4 h post-injury.
Conclusion: These results suggest that post-traumatic coagulopathy, identified by elevated admission INR, is associated with a markedly differential inflammatory response when compared to patients that present without TIC despite similar injury patterns. Reduced dynamic network connectivity in the TIC patients suggests a discoordinated inflammatory response that might promote immune dysfunction and hence worse outcome.