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中华重症医学电子杂志

中华重症医学电子杂志 ›› 2023, Vol. 09 ›› Issue (02) : 168 -177. doi: 10.3877/cma.j.issn.2096-1537.2023.02.007

临床研究

血浆肝素结合蛋白在脓毒症早期诊断和预后预测中的应用
蔡荇, 张文娟, 於江泉, 郑瑞强†()   
  1. 225001　江苏扬州，江苏省苏北人民医院重症医学科
  • 收稿日期:2022-06-08 出版日期:2023-05-28
  • 通信作者: 郑瑞强
  • 基金资助:
    江苏省卫健委科研项目(Z2020055)

Study on the prognostic value of plasma heparin-binding protein in the early diagnosis and prognosis of sepsis

Xing Cai, Wenjuan Zhang, Jiangquan Yu, Ruiqiang Zheng†()   

  1. Department of Critical Care Medicine, Northern Jiangsu People's Hospital in Jiangsu Province, Yangzhou 225001, China
  • Received:2022-06-08 Published:2023-05-28
  • Corresponding author: Ruiqiang Zheng
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蔡荇, 张文娟, 於江泉, 郑瑞强. 血浆肝素结合蛋白在脓毒症早期诊断和预后预测中的应用[J/OL]. 中华重症医学电子杂志, 2023, 09(02): 168-177.

Xing Cai, Wenjuan Zhang, Jiangquan Yu, Ruiqiang Zheng. Study on the prognostic value of plasma heparin-binding protein in the early diagnosis and prognosis of sepsis[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2023, 09(02): 168-177.

目的

分析血浆肝素结合蛋白（HBP）对脓毒症的早期诊断及预后预测的价值。

方法

采用前瞻性观察性研究方法，收集2019年6月至2021年6月在江苏省苏北人民医院重症医学科确诊感染的患者198例，根据病情严重程度分为非脓毒症组（48例）、脓毒症组（52例）、脓毒症休克组（98例）。另外选择同期入住我科的40例非感染性疾病患者作为对照组。对比分析各组患者HBP、降钙素原（PCT）、C反应蛋白（CRP）、白细胞计数（WBC）、乳酸（Lac）水平的差异，绘制受试者工作特征（ROC）曲线评估各指标对脓毒症诊断及28 d生存情况的预测价值；采用logistic回归分析明确影响脓毒症预后的因素。

结果

入组时脓毒症休克组患者HBP水平显著高于其他3组，且脓毒症组患者的水平也显著高于非脓毒症组，差异有统计学意义（P＜0.05）。当取最佳截断值35.8 ng/ml时，HBP从感染群体中筛选出脓毒症患者的曲线下面积（AUC）为0.922。将所有脓毒症患者根据28 d后的存活情况分为死亡组（29例）和存活组（121例），死亡组患者的HBP和Lac水平均高于存活组，差异有统计学意义（P＜0.05），而2组间PCT、CRP和WBC比较，差异无统计学意义（P＞0.05）。当HBP＞97.6 ng/ml时，脓毒症病死率明显升高，预测患者28 d病死率的AUC为0.750，敏感度为65.5%，特异度为77.7%。死亡组在入组0、24、48、72 h血浆HBP水平均高于存活组，差异有统计学意义（P＜0.05），而死亡组血浆HBP水平在各时间点与前一时间点相比，差异均无统计学意义（P＞0.05）。

结论

HBP可作为诊断脓毒症的早期生物标志物，并且与PCT、CRP、WBC和Lac相比有更好的诊断价值。同时，HBP水平及变化趋势与脓毒症疾病严重程度相关，可用来评价脓毒症患者的预后情况。

关键词: 肝素结合蛋白, 脓毒症, 脓毒症休克, 生物标志物
Objective

To evaluate the value of plasma heparin binding protein (HBP) in the early diagnosis of sepsis, and to explore the application value of HBP for the severity and prognosis assessment of sepsis.

Methods

A prospective observational study was conducted in Department of Critical Care Medicine of Northern Jiangsu People's Hospital. One hundred and ninety-eight patients with confirmed infections from June 2019 to June 2021 were enrolled in this study. According to the illness severity of sepsis, patients were assigned as non-sepsis (n=48), sepsis (n=52) and septic shock (n=98). Forty patients in the same period without infection were selected as control group. The differences in HBP, procalcitonin (PCT), C-reactive protein (CRP), white blood cell count (WBC) and lactate (Lac) levels were compared and analyzed. The prognostic values on sepsis diagnosis and 28-day mortality were evaluated through drawing receiver operating characteristic (ROC) curve. Logistic regression analysis was used to clarify the factors affecting the prognosis of sepsis.

Results

The plasma level of HBP was obviously elevated in septic shock group than patients in other three groups (P＜0.05), while patients in sepsis group had higher HBP than patients in non-sepsis group (P＜0.05). Take an optimal cutoff value of 35.8 ng/ml, the area under the curve (AUC) for HBP to distinguish sepsis from from non-sepsis was 0.922. The levels of HBP and Lac were also significantly elevated in non-survivors compared to survival group (P＜0.05). Ho sever, no significant differences of PCT, CRP and WBC levels were found between the two groups. Plasma HBP＞97.6 ng/ml was associated with elevated mortality, AUC of HBP predicting 28-day mortality of sepsis patients was 0.750, with a sensitivity of 65.5% and a specificity of 77.7%. The plasma HBP levels in death group were higher than those in survival group at 0 h, 24 h, 48 h and 72 h after admission (P＜0.05). Meanwhile, in death group, the plasma HBP level showed no statistical differences in each time point compared with that in the previous time point (P＞0.05).

Conclusion

HBP can be a better and more specific early predictor of sepsis compared with PCT, CRP, WBC and Lactate. Meanwhile, the level and tendency of HBP has valuable to evaluate the severity of sepsis and mortality.

Key words: Heparin-binding protein, Sepsis, Septic shock, Biomarkers
表1 各组研究对象一般资料比较
一般资料 对照组（40例） 非脓毒症组（48例） 脓毒症组（52例） 脓毒症休克组（98例） 统计值 P值
年龄（岁，
x¯
±s）		 62.7±6.0 60.6±10.5 62.9±10.0 63.6±9.5 F=1.095 0.352
性别［男，例（%）］ 18（45.0） 24（50.0） 32（61.5） 52（53.1） χ2=2.722 0.736
基础疾病［例（%）］
高血压 10（25.0） 17（35.4） 12（23.1） 28（28.6） χ2=2.120 0.548
糖尿病 7（17.5） 11（22.9） 13（25.0） 31（31.6） χ2=3.378 0.337
冠心病 5（12.5） 8（16.7） 6（11.5） 19（19.4） χ2=1.991 0.574
感染来源［例（%）］
呼吸系统 - 32（66.7） 27（51.9） 50（51.0） χ2=3.466 0.177
腹腔脏器 - 4（8.3） 8（15.4） 15（15.3） χ2=1.513 0.469
泌尿系统 - 7（14.6） 10（19.2） 16（16.3） χ2=0.404 0.817
血流感染 - 0 3（5.8） 8（8.2） χ2=4.098 0.129
其他 - 5（10.4） 4（7.7） 9（9.2） χ2=0.226 0.893
APACHEⅡ评分（分，
x¯
±s）		 14.7±5.3 15.9±4.9 16.5±3.8 22.1±6.2 F=27.088 ＜0.001
图1 各组研究对象感染标志物水平的比较。图a~e分别为HBP、PCT、CRP、WBC、Lac水平注：HBP为肝素结合蛋白；PCT为降钙素原；CRP为C反应蛋白；WBC为白细胞计数；Lac为乳酸
表2 各组研究对象HBP、PCT、CRP、WBC和Lac水平比较［M（Q25，Q75）］
组别 例数 HBP（ng/ml） PCT（ng/ml） CRP（mg/L） WBC（×109/L） Lac（mmol/L）
对照组 40 7.6（5.9，10.8） 0.6（0.2，1.0） 11.0（9.1，16.9） 9.9（1.7，11.3） 2.1（1.6，2.9）
非脓毒症组 48 16.3（5.9，31.2）a 1.3（0.5，2.9）a 44.5（34.0，64.5）a 11.2（7.7，13.4） 1.6（1.1，2.5）
脓毒症组 52 36.1（29.9，45.9）ab 8.1（2.6，23.0）ab 62.1（45.3，77.8）ab 14.8（7.7，19.7）ab 2.4（1.6，3.9）ab
脓毒症休克组 98 86.9（54.9，131.0）abc 32.5（16.7，62.0）abc 101.7（74.8，144.3）abc 14.8（9.9，23.8）ab 3.2（2.3，7.0）abc
H值 168.727 145.241 162.460 26.029 41.925
P值 ＜0.001 ＜0.001 ＜0.001 ＜0.001 ＜0.001
表3 非脓毒症组、脓毒症组和脓毒症休克组0、24、48、72 h血浆HBP水平比较［ng/ml，M（Q25，Q75）］
组别 例数 0 h 24 h 48 h 72 h H值 P值
非脓毒症组 48 16.3（5.9，31.2） 11.4（5.9，20.8） 10.8（5.9，16.1） 5.9（5.9，8.4） 30.616 ＜0.001
脓毒症组 52 36.1（29.9，45.9）a 30.6（21.4，34.9）a 21.0（15.2，31.2）a 10.7（9.3，19.8）a 77.260 ＜0.001
脓毒症休克组 98 86.9（55.0，131.0）ab 56.0（35.8，89.3）ab 43.1（24.8，72.9）ab 24.6（16.2，46.7）ab 106.611 ＜0.001
H值 113.882 109.381 85.532 110.478
P值 ＜0.001 ＜0.001 ＜0.001 ＜0.001
图2 HBP、PCT、CRP、WBC和Lac从感染群体中筛选出脓毒症患者的ROC曲线注：HBP为肝素结合蛋白；PCT为降钙素原；CRP为C反应蛋白；WBC为白细胞计数；Lac为乳酸
表4 不同感染指标对脓毒症的诊断效能
感染指标 临界值 敏感度（%） 特异度（%） AUC 95%CI P值
HBP 35.8 ng/ml 84.7 87.5 0.922 0.873~0.971 ＜0.001
PCT 3.58 ng/ml 85.3 81.2 0.899 0.851~0.947 ＜0.001
CRP 66.5 mg/L 72.7 83.3 0.858 0.803~0.914 ＜0.001
WBC 13.8×109/L 56.0 83.7 0.671 0.598~0.744 ＜0.001
Lac 1.95 mmol/L 82.7 62.5 0.728 0.634~0.821 ＜0.001
图3 28 d存活组与死亡组感染标志物水平的比较。图a~e分别为HBP、PCT、CRP、WBC、Lac水平注：HBP为肝素结合蛋白；PCT为降钙素原；CRP为C反应蛋白；WBC为白细胞计数；Lac为乳酸
图4 各感染标志物预测脓毒症患者28 d病死率的ROC曲线注：HBP为肝素结合蛋白；PCT为降钙素原；CRP为C反应蛋白；WBC为白细胞计数；Lac为乳酸；ROC为受试者工作特征
表5 死亡组和存活组0、24、48、72 h血浆HBP水平［ng/ml，M（Q25，Q75）］
组别 例数 0 h 24 h 48 h 72 h H值 P值
死亡组 29 112.2（56.9，192.8） 86.0（50.1，129.0） 72.0（35.0，106.6） 66.0（38.5，89.0） 14.364 0.002
存活组 121 58.8（36.2，95.9） 41.0（28.5，66.0）a 25.0（18.5，45.1）a 17.4（10.3，24.6）a 161.165 ＜0.001
Z值 4.172 4.344 5.348 6.642
P值 ＜0.001 ＜0.001 ＜0.001 ＜0.001
表6 28 d病死率影响因素的logistic多因素回归分析
影响因素 B值 S.E.值 Wald χ2值 OR 95%CI P值
APACHEⅡ评分（分） 0.052 0.040 1.662 1.053 0.973~1.140 0.197
HBP（ng/ml） 0.008 0.003 6.569 1.008 1.002~1.014 0.010
Lac（mmol/L） 0.218 0.062 12.429 1.244 1.102~1.404 ＜0.001
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