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中华危重症医学杂志(电子版) ›› 2017, Vol. 10 ›› Issue (06) : 367 -373. doi: 10.3877/cma.j.issn.1674-6880.2017.06.002

所属专题： 文献；

论著

恶性血液病感染患者内皮细胞损伤、炎症因子及凝血指标的临床研究
师灵灵1, 韩艳秋1,†()   
  1. 1. 010059　呼和浩特，内蒙古医科大学附属医院血液内科
  • 收稿日期:2017-04-26 出版日期:2017-12-01
  • 通信作者: 韩艳秋
  • 基金资助:
    内蒙古自治区草原英才创新团队项目(2013-9)

Clinical study on endothelial cell damage, inflammatory factors and coagulation indicators for sepsis in patients with hematological malignancies

Lingling Shi1, Yanqiu Han1,†()   

  1. 1. Department of Hematology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, China
  • Received:2017-04-26 Published:2017-12-01
  • Corresponding author: Yanqiu Han
  • About author:
    Corresponding author: Han Yanqiu, Email:
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引用本文：

师灵灵, 韩艳秋. 恶性血液病感染患者内皮细胞损伤、炎症因子及凝血指标的临床研究[J/OL]. 中华危重症医学杂志(电子版), 2017, 10(06): 367-373.

Lingling Shi, Yanqiu Han. Clinical study on endothelial cell damage, inflammatory factors and coagulation indicators for sepsis in patients with hematological malignancies[J/OL]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(06): 367-373.

目的

探讨恶性血液病感染患者内皮细胞损伤、炎症因子及凝血标记物的表达，三者的关系及临床意义分析。

方法

选取内蒙古医科大学附属医院2015年5月至12月确诊为恶性血液病（除急性早幼粒细胞白血病）的住院患者113例，按感染程度分未感染组（43例）、普通感染组（31例）和脓毒症组（39例）。检测三组患者一般资料，炎症指标[降钙素（PCT）、超敏C反应蛋白（hs-CRP）、白细胞介素6（IL-6）]、凝血指标[凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、D-二聚体、抗凝血酶Ⅲ（AT-Ⅲ）]和内皮损伤标记物[血管性血友病因子（vWF）]，并进行比较。绘制受试者工作特征曲线（ROC），采用Pearson相关系数进行相关性分析。

结果

三组间性别比、年龄、体温、WBC、中性粒细胞计数（NEUT）的比较，差异均无统计学意义（P均> 0.05）。而与未感染组相比，普通感染组和脓毒症组RBC [（3.8 ± 1.0）× 1012/L、（2.9 ± 1.0）× 1012/L、（2.9 ± 0.7）× 1012/L]、血红蛋白水平[（117 ± 24）g/L、（88 ± 26）g/L、（88 ± 20）g/L]均显著降低（P均< 0.05）。炎症指标比较显示，与未感染组相比，普通感染组和脓毒症组hs-CRP[（4 ± 3）mg/L、（44 ± 20）mg/L、（168 ± 65）mg/L]、PCT[0.04（0.02，0.08）μg/L、0.16（0.06，0.38）μg/L、0.80（0.35，2.48）μg/L]、IL-6 [（6 ± 4）ng/L、（36 ± 34）ng/L、（150 ± 119）ng/L]、CD64阳性率[（36 ± 21）%、（53 ± 13）%、（69 ± 20）%]均显著升高，且脓毒症组升高更多（P均< 0.05）。ROC曲线分析结果显示，炎症指标PCT、CD64阳性率、IL-6、hs-CRP的曲线下面积（AUC）、灵敏性、特异性依次减低。凝血指标和内皮损伤指标比较显示，与未感染组相比，普通感染组和脓毒症组PT[（11.8 ± 1.3）s、（13.6 ± 4.9）s、（14.0 ± 2.4）s]、APTT[（29 ± 8）s、（35 ± 10）s、（41 ± 9）s]、D-二聚体[0.44（0.34，1.58）mg/L、2.35（1.01，4.12）mg/L、5.24（2.13，9.87）mg/L]、vWF[（126 ± 53）%、（194 ± 66）%、（354 ± 154）%]均显著升高，而AT-Ⅲ活性[（101 ± 11）%、（99 ± 14）%、（82 ± 16）%]显著降低（P均< 0.05）。Pearson相关性分析显示，脓毒症组PCT与PT、APTT均呈正相关（r = 0.432、0.223，P均< 0.05），与AT-Ⅲ呈负相关（r = -0.394，P < 0.001）；CD64阳性率与PT、APTT、D-二聚体均呈正相关（r = 0.302、0.457、0.452，P均< 0.05），与AT-Ⅲ呈负相关（r = -0.436，P < 0.001）。脓毒症组vWF与炎症指标PCT、CD64阳性率均呈正相关（r = 0.341、0.681，P均< 0.001)，与凝血指标APTT、D-二聚体也呈正相关（r = 0.317、0.291，P均< 0.05），而与AT-Ⅲ呈负相关（r = -0.327，P < 0.001）。

结论

PCT和CD64可为恶性血液病感染患者早期诊断提供更准确的依据。多种标志物联合检测能更准确地诊断感染及预测发展成脓毒症的可能性。

关键词: 脓毒症, 恶性血液病, 内皮细胞损伤, 炎症因子, 凝血紊乱
Objective

To investigate the expression of endothelial cell damage, inflammation factors and coagulation indicators for sepsis in patients with hematological malignancies, and to explore the correlation and clinical significance among them.

Methods

A total of 113 hospitalized patients who were diagnosed with hematological malignancies (except for acute promyelocytic leukemia), were selected in the Affiliated Hospital of Mongolia Medical University from May 2015 to December 2015. According to the degree of infection, these patients were divided into three groups: non-infection group (n = 43), common infection group (n = 31) and sepsis group (n = 39). The general physical data, inflammation indices [procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6)], coagulation related markers [prothrombin time (PT), activated partial thromboplatin time (APTT), D-dimer, antithrombinⅢ (AT-Ⅲ)] and endothelial injury marker [von Willebrand factor (vWF)] were determined and compared among the three groups. The receiver operating characteristic curve (ROC) was drawn. Correlation analysis was performed using Pearson correlation coefficient.

Results

The comparison of gender, age, temperature, white blood cell count (WBC) and neutrophil count (NEUT) were not significantly different among these groups (all P > 0.05). Compared with the non-infection group, the red blood cell count (RBC) [(3.8 ± 1.0) × 1012/L, (2.9 ± 1.0) × 1012/L, (2.9 ± 0.7) × 1012/L], hemoglobin [(117 ± 24) g/L, (88 ± 26) g/L, (88 ± 20) g/L] decreased significantly in the other two groups. The inflammation indices demonstrated that to compare with the non-infection group, hs-CRP [(4 ± 3) mg/L, (44 ± 20) mg/L, (168 ± 65) mg/L], PCT [0.04 (0.02, 0.08) μg/L, 0.16 (0.06, 0.38) μg/L, 0.80 (0.35, 2.48) μg/L]、IL-6 [(6 ± 4) ng/L, (36 ± 34) ng/L, (150 ± 119) ng/L], and the positive rates of CD64 [(36 ± 21)%, (53 ± 13)%, (69 ± 20)%] in the common infection group and sepsis group all increased, and increased greater in the sepsis group (all P < 0.05). ROC curve analysis showed that the area under curve (AUC), sensitivity and specificity of PCT, the positive rate of CD64, IL-6, and hs-CRP reduced in turn. The coagulation related markers and endothelial injury marker demonstrated that in comparison with the non-infection group, PT [(11.8 ± 1.3) s, (13.6 ± 4.9) s, (14.0 ± 2.4) s], APTT [(29 ± 8) s, (35 ± 10) s, (41 ± 9) s], D-dimer [0.44 (0.34, 1.58) mg/L, 2.35 (1.01, 4.12) mg/L, 5.24 (2.13, 9.87) mg/L], vWF [(126 ± 53)%, (194 ± 66)%, (354 ± 154)%] were all higher in the common infection group and sepsis group, while the activity of AT-Ⅲ was lower in these two groups (all P < 0.05). Pearson correlation analysis showed the level of PCT in the sepsis group positively correlated with PT, APTT (r = 0.432, 0.223; both P < 0.05), and negatively correlated with AT-Ⅲ (r = -0.394, P < 0.001); the positive rate of CD64 positively correlated with PT, APTT, D-dimer (r = 0.302, 0.457, 0.452; all P < 0.05), and negatively correlated with AT-Ⅲ (r = -0.436, P < 0.001). The vWF in the sepsis group positively correlated with the inflammation indices PCT, CD64 (r = 0.341, 0.681; both P < 0.001), and also correlated with the coagulation related markers APTT, D-dimer (r = 0.317, 0.291; both P < 0.05), but negatively correlated with AT-Ⅲ (r = -0.327, P < 0.001).

Conclusions

PCT and CD64 can provide more accurate basis for early diagnosis of infection in patients with malignant hematological diseases. Multiple markers can more accurately detect infection and predict the possibility of sepsis.

Key words: Sepsis, Hematological malignancies, Endothelial cell injury, Inflammatory factors, Coagulation disorders
表1 三组恶性血液病患者一般资料的比较（ ± s）
组别 例数 性别比（男/女） 年龄（岁） 体温（℃） WBC（× 109/L） RBC（× 1012/L） 血红蛋白水平（g/L） NEUT（× 109/L）
未感染组 43 16/27 49 ± 14 36.4 ± 0.7 6.25（3.67，7.54） 3.8 ± 1.0 117 ± 24 3.27（2.06，5.17）
普通感染组 31 19/12 57 ± 15 37.6 ± 1.0 4.10（2.94，8.75） 2.9 ± 1.0a 88 ± 26a 2.45（1.09，3.96）
脓毒症组 39 24/15 57 ± 18 38.3 ± 0.9 2.19（1.06，7.01） 2.9 ± 0.7a 88 ± 20a 1.21（0.13，3.53）
F/χ2/Z值 ? 6.236 3.166 2.481 2.787 13.030 19.312 2.666
P值 ? 0.054 0.056 0.324 0.698 < 0.001 < 0.001 0.412
表2 三组恶性血液病患者炎症指标的比较（ ± s）
组别 例数 hs-CRP（mg/L） PCT（μg/L） IL-6（ng/L） CD64阳性率（%）
未感染组 43 4±3 0.04（0.02，0.08） 6±4 36 ± 21
普通感染组 31 44 ± 20a 0.16（0.06，0.38）a 36 ± 34a 53 ± 13a
脓毒症组 39 168 ± 65ab 0.80（0.35，2.48）ab 150 ± 119ab 69 ± 20ab
F/Z值 ? 188.306 4.639 43.545 29.632
P值 ? < 0.001 < 0.001 < 0.001 < 0.001
表3 三组恶性血液病患者凝血指标和内皮损伤指标的比较（ ± s）
组别 例数 PT（s） APTT（s） D-二聚体（mg/L） AT-Ⅲ（%） vWF（%）
未感染组 43 11.8 ± 1.3 29 ± 8 0.44（0.34，1.58） 101 ± 11 126 ± 53
普通感染组 31 13.6 ± 4.9a 35 ± 10a 2.35（1.01，4.12）a 99 ± 14a 194 ± 66a
脓毒症组 39 14.0 ± 2.4ab 41 ± 9ab 5.24（2.13，9.87）ab 82 ± 16ab 354 ± 154ab
F/χ2/Z值 ? 6.376 19.769 3.402 20.504 52.248
P值 ? < 0.001 < 0.001 < 0.001 < 0.001 < 0.001
表4 恶性血液病患者炎症指标诊断性能比较
指标 临界值 AUC 95%CI 灵敏度（%） 特异度（%） 标准误 P1值 Z值 P2值
PCT（μg/L） 3.13 0.999 0.965 ~ 1.000 99.20 98.90 0.040 < 0.001 参考
hs-CRP（mg/L） 151.21 0.865 0.788 ~ 0.922 89.60 81.20 0.004 0.038 0.981 0.038
IL-6（ng/L） 138.78 0.949 0.891 ~ 0.982 91.10 92.30 0.025 0.046 0.977 0.046
CD64阳性率（%） 65.71 0.976 0.982 ~ 0.995 96.60 95.80 0.051 0.001 0.999 0.001
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