Time-dependent changes in proinflammatory mediators are associated with trauma-related venous thromboembolism
Atharwa R. Mankame, Kelly E. Sanders, Jessica C. Cardenas- Critical Care and Intensive Care Medicine
- Emergency Medicine
Abstract
Background
Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTE) after major trauma.
Objectives
Identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients.
Methods
We performed a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios (PROPPR) study. Plasma levels of 27 cytokines/chemokines were measured by BioPlex at admission and 2, 4, 6, 12, 24, 48, and 72 hours later. Patients who died from exsanguination or within 24 hours were excluded. Mann-Whitney tests were performed to assess No-VTE and VTE groups at each time point. Multivariable logistic regression was used to determine the adjusted effects of inflammatory mediators on VTE risk.
Results
86 (15%) of the 575 patients included developed VTE. Interleukins IL-1ra, IL-6, IL-8, IL-10, Eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon-gamma inducible protein (IP-10), monocyte chemoattractant protein (MCP-1), and chemokine ligand 5 (RANTES) were all significantly increased among VTE patients. Multivariable analyses demonstrated that IL-6, IL-8, IP-10, and MCP-1 were independently associated with VTE. Cox proportional hazards modeling identified IL-6, IL-8, and MCP-1 as independent predictors of accelerated VTE development. We identified significant correlations between inflammation and markers of coagulation and endothelial activation.
Conclusions
Sustained, systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.