Association of the Circulating Supar Levels with Inflammation, Fibrinolysis, and Outcome in Severe Burn Patients

Abstract

Background: Hyperfibrinolysis and pro/anti-inflammatory imbalance usually occur in the early stage of severe burns. Soluble urokinase-type plasminogen activator receptor (suPAR) is involved in fibrinolysis and inflammation. To date, the levels of circulating suPAR in non-survivors with severe burns remain unknown. This study aimed to investigate the early association between circulating suPAR levels and biomarkers of fibrinolysis, pro/anti-inflammatory, and prognosis. Methods: Sixty-four consecutive Chinese patients with severe burns and 26 healthy volunteers were enrolled in a prospective observational cohort. Clinical characteristics and laboratory data were collected prospectively. Blood samples were collected at 48 h post-burn, and suPAR and biomarkers of pro/anti-inflammatory and fibrinolysis were detected by enzyme-linked immunosorbent assays. Important indicators between non-survivors and survivors were compared. Linear regression analysis was performed to screen variables associated with suPAR. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were performed to evaluate the prognostic value of suPAR. Result: Compared with the control group, the circulating suPAR levels in the survivors (P < 0.001) and non-survivors (P ¼ 0.017) were higher. Compared with survivors, non-survivors had lower circulating suPAR levels at 48 h post-burn, and they showed a higher degree of fibrinolysis (higher D-dimer) and a lower TNF-a/IL-10 ratio. According to linear regression analysis, the variables independently associated with a lower suPAR level were lower platelet factor 4 (PF-4), urokinase-type plasminogen activator (uPA), and TNF-a/IL-10 levels and a higher D-dimer level. Logistic regression and ROC analyses indicated that a suPAR level 4.70 mg/L was independently associated with 30-day mortality. Conclusion: Low circulating suPAR levels at 48 h post-burn in severe burn patients may reflect decreased TNF-a/IL-10 ratio and increased hyperfibrinolysis. suPAR can predict 30-day mortality in patients with severe burn. KEYWORDS-Burn, hyperfibrinolysis, IL-10, pro/anti-inflammatory imbalance, suPAR ABBREVIATIONS-ABSI score-abbreviated burn severity index score; APTT-activated partial prothrombin time; AUCarea under the curve; CRP-C-reactive protein; IFN-g-interferon g; IL-interleukin; INR-international standardized ratio; ns-no significance; PAI-1-plasminogen activator inhibitor-1; PF-4-platelet factor 4; PT-prothrombin time; ROCreceiver operating characteristic curve; SOFA-sequential organ failure assessment; sP-selectin-soluble P-selectin; suPAR-soluble urokinase-type plasminogen activator receptor; TBSA-total burn surface area; TNF-a-tumor necrosis factor a; TT-thrombin time; uPA-urokinase-type plasminogen activator

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“…Patients experiencing burns typically present complex resuscitation problems. Lin et al (10) from Fujian Medical University examine markers of fibrinolysis and pro- inflammatory and anti-inflammatory mediator balance in patients experiencing severe burns. A particular interest of this group is soluble urokinase-type plasminogen activator receptor (suPAR), a mediator of fibrinolysis and inflammation (10).…”

“…Lin et al (10) from Fujian Medical University examine markers of fibrinolysis and pro- inflammatory and anti-inflammatory mediator balance in patients experiencing severe burns. A particular interest of this group is soluble urokinase-type plasminogen activator receptor (suPAR), a mediator of fibrinolysis and inflammation (10). Sixty-four patients with burns measuring at least 30% of the total body surface area were compared with 26 healthy volunteers.…”