Vollrath Jan Tilmann, Marzi Ingo, Herminghaus Anna, Lustenberger Thomas, Relja Borna
Department of Trauma, Hand and Reconstructive Surgery, Goethe University, 60590 Frankfurt, Germany.
Department of Anesthesiology, Duesseldorf University Hospital, 40225 Duesseldorf, Germany.
J Clin Med. 2020 Apr 24;9(4):1230. doi: 10.3390/jcm9041230.
Sepsis frequently occurs after major trauma and is closely associated with dysregulations in the inflammatory/complement and coagulation system. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a dual role as an anti-fibrinolytic and anti-inflammatory factor by downregulating complement anaphylatoxin C5a. The purpose of this study was to investigate the association between TAFI and C5a levels and the development of post-traumatic sepsis. Furthermore, the predictive potential of both TAFI and C5a to indicate sepsis occurrence in polytraumatized patients was assessed.
Upon admission to the emergency department (ED) and daily for the subsequent ten days, circulating levels of TAFI and C5a were determined in 48 severely injured trauma patients (injury severity score (ISS) ≥ 16). Frequency matching according to the ISS in septic vs. non-septic patients was performed. Trauma and physiologic characteristics, as well as outcomes, were assessed. Statistical correlation analyses and cut-off values for predicting sepsis were calculated.
Fourteen patients developed sepsis, while 34 patients did not show any signs of sepsis (no sepsis). Overall injury severity, as well as demographic parameters, were comparable between both groups (ISS: 25.78 ± 2.36 no sepsis vs. 23.46 ± 2.79 sepsis). Septic patients had significantly increased C5a levels (21.62 ± 3.14 vs. 13.40 ± 1.29 ng/mL; < 0.05) and reduced TAFI levels upon admission to the ED (40,951 ± 5637 vs. 61,865 ± 4370 ng/mL; < 0.05) compared to the no sepsis group. Negative correlations between TAFI and C5a ( = 0.0104) and TAFI and lactate ( = 0.0423) and positive correlations between C5a and lactate ( = 0.0173), as well as C5a and the respiratory rate ( = 0.0266), were found. In addition, correlation analyses of both TAFI and C5a with the sequential (sepsis-related) organ failure assessment (SOFA) score have confirmed their potential as early sepsis biomarkers. Cut-off values for predicting sepsis were 54,857 ng/mL for TAFI with an area under the curve (AUC) of 0.7550 ( = 0.032) and 17 ng/mL for C5a with an AUC of 0.7286 ( = 0.034).
The development of sepsis is associated with early decreased TAFI and increased C5a levels after major trauma. Both elevated C5a and decreased TAFI may serve as promising predictive factors for the development of sepsis after polytrauma.
脓毒症常发生于严重创伤后，与炎症/补体及凝血系统失调密切相关。凝血酶激活的纤溶抑制物（TAFI）通过下调补体过敏毒素C5a发挥抗纤溶和抗炎双重作用。本研究旨在探讨TAFI与C5a水平之间的关联以及创伤后脓毒症的发生情况。此外，还评估了TAFI和C5a对多发伤患者脓毒症发生的预测潜力。
对48例严重创伤患者（损伤严重度评分（ISS）≥16）在急诊科入院时及随后十天每天测定循环中TAFI和C5a水平。根据ISS对脓毒症患者与非脓毒症患者进行频率匹配。评估创伤和生理特征以及预后。计算预测脓毒症的统计相关性分析和临界值。
14例患者发生脓毒症，34例患者未出现任何脓毒症迹象（无脓毒症）。两组患者的总体损伤严重程度以及人口统计学参数具有可比性（ISS：无脓毒症组为25.78±2.36，脓毒症组为23.46±2.79）。与无脓毒症组相比，脓毒症患者在急诊科入院时C5a水平显著升高（21.62±3.14 vs. 13.40±1.29 ng/mL；P<0.05），TAFI水平降低（40,951±5637 vs. 61,865±4370 ng/mL；P<0.05）。发现TAFI与C5a之间呈负相关（r = 0.0104），TAFI与乳酸之间呈负相关（r = 0.0423），C5a与乳酸之间呈正相关（r = 0.0173），以及C5a与呼吸频率之间呈正相关（r = 0.0266）。此外，TAFI和C5a与序贯（脓毒症相关）器官衰竭评估（SOFA）评分的相关性分析证实了它们作为早期脓毒症生物标志物的潜力。预测脓毒症的TAFI临界值为54,857 ng/mL，曲线下面积（AUC）为0.7550（P = 0.032），C5a临界值为17 ng/mL，AUC为０.7286（P = 0.034）。
脓毒症的发生与严重创伤后早期TAFI降低和C5a水平升高有关。C5a升高和TAFI降低均可能是多发伤后脓毒症发生的有前景的预测因素。
