Inflammatory response to trauma: implications for coagulation and resuscitation

Abstract

Purpose of review: Recent studies have changed our understanding of the timing and interactions of the inflammatory processes and coagulation cascade following severe trauma. This review highlights this information and correlates its impact on the current clinical approach for fluid resuscitation and treatment of coagulopathy for trauma patients.

Recent findings: Severe trauma is associated with a failure of multiple biologic emergency response systems that includes imbalanced inflammatory response, acute coagulopathy of trauma, and endovascular glycocalyx degradation with microcirculatory compromise. These abnormalities are all interlinked and related. Recent observations show that after severe trauma: proinflammatory and anti-inflammatory responses are concomitant, not sequential and resolution of the inflammatory response is an active process, not a passive one. Understanding these interrelated processes is considered extremely important for the development of future therapies for severe trauma in humans.

Summary: Traumatic injuries continue to be a significant cause of mortality worldwide. Recent advances in understanding the mechanisms of end-organ failure, and modulation of the inflammatory response has important clinical implications regarding fluid resuscitation and treatment of coagulopathy.

Figure 1. The impact of coagulation on inflammation and the impact of inflammation on coagulation

Coagulation triggers platelet activation and leads to P selectin and CD40 ligand expression platelet surface. Ischaemia leads to cell death and the release of histones and HMGB1, both of which augment inflammation. Inflammation in turn leads to tissue factor induction, leukocyte adhesion, thrombomodulin down regulation, and complement activation, Thus, coagulation increases inflammation that in turn increases coagulation. Adapted from (44).

Figure 2. The vicious cycle of tissue damage and inflammatory response

Tissue damage causes a local inflammatory response that may become more systemic. This systemic inflammation leads to endothelial damage at distant sites (including the lungs). The resulting tissue edema, decreased microperfusion and tissue hypoxia leads to more tissue damage.

Figure 3. Endothelial glycocalyx damage associated with systemic inflammation

The normal functions of the Endothelial Surface Layer (ESL) to maintain homeostasis are lost when glycocalyx degradation occurs. Loss of plasma proteins and fluid to the interstitium, inappropriate activation of coagulation and immune competent cells all contribute to edema and microcirculatory compromise.