60 A Maladaptive Fibrinolytic Phenotype Is Associated with Inflammatory Cytokines and Mortality After Burn Injury

TL;DR

After severe burns, abnormal blood clot breakdown is linked to higher inflammation and increased risk of death.

Contribution

This study identifies a link between maladaptive fibrinolytic phenotypes and elevated inflammatory cytokines after burn injury.

Findings

A maladaptive fibrinolytic phenotype was associated with higher mortality (26.5% vs 7.8%).

IL-6 and IL-10 levels were elevated in patients with maladaptive fibrinolytic phenotypes.

Fibrinolytic dysfunction correlates with increased inflammatory response after burn injury.

Abstract

Burn injury results in a multifactorial response characterized by dysregulation of the inflammatory and fibrinolytic systems. This inflammatory response is characterized by changes in the levels of cytokines with elevated levels of pro-inflammatory cytokines portending a poorer prognosis. Abnormal fibrinolytic function following burn injury is also associated with mortality risk. However, the relationship between fibrinolytic function and the inflammatory response up to 48 hours post-burn has not been established. This study aimed to identify a relationship between a maladaptive fibrinolytic phenotype and inflammatory cytokines, and their association with mortality.

Patients presenting to a regional burn center within 4 hours of thermal injury were included. Blood was drawn at hospital admission and sequentially at hours 2, 4, 8, 12, 24, 36, and 48. Thromboelastography (Rapid TEG) was performed. Percent clot lysis 30 minutes after maximum clot strength (LY30) was used to characterize fibrinolytic phenotypes: shutdown (SD; < 0.6), physiologic (PHYS; 0.6-7.7), and hyperfibrinolytic (HF; >7.7). Phenotype patterns that remained in or transitioned to HF or SD at hour 48, or the latest available time point were considered maladaptive. A multivex assay was used to obtain levels of interleukin 6 (IL-6), interleukin 10 (IL-10), and tumor necrosis factor alpha (TNF-α). Cytokine patterns by fibrinolytic phenotypes and mortality status were examined using mixed effects model.

Of 98 patients included, the mean TBSA burned was 20.9% (21.8). Overall mortality was 14.3%. From admission to hour 48, levels of IL-6 and TNF-α increased from 73.1 to 178.9 pg/mL and 1.3 to 1.8 pg/mL respectively, while levels of IL-10 decreased from 23.5 to 7.5 pg/mL, but there were no statistically significant differences in cytokine levels among the three fibrinolytic phenotypes at any time point. A maladaptive phenotype pattern (n=34, 34.7%) was associated with higher mortality compared to those with an adaptive phenotype (n=64, 65.3%) (26.5% vs 7.8%; p=0.02). Compared to an adaptive phenotype, IL-6 levels were higher at hours 24 (443.1 vs 121.8 pg/mL; p=0.03) and 36 (436.1 vs 90.2 pg/mL; p=0.02), while IL-10 levels were higher at hours 8 (7.2 vs 1.5 pg/mL; p=0.03) in patients with a maladaptive phenotype. Levels of TNF-α were not different between phenotypes.

After burn injury, a maladaptive fibrinolytic phenotype is associated with elevated IL-6 and IL-10, and mortality. Fibrinolytic dysregulation is associated with increased cytokine response in severe burn. Further biochemical studies are needed to explore the relationships between fibrinolysis and inflammation.

Correction or treatment of burn induced fibrinolytic dysfunction may mitigate the hyperinflammatory response after burn injury.

Department of Defense Award Number W911NF-10-1-0459