Advances in Clinical Medicine
Vol. 10  No. 04 ( 2020 ), Article ID: 35042 , 7 pages
10.12677/ACM.2020.104076

Diagnostic Value of Monocyte-Large Platelet Ratio in Patients with AECOPD and PE

Yuanyuan Liu, Zhaozhong Cheng

Respiratory Department of the Affiliated Hospital of Qingdao University Medical College, Qingdao Shandong

Received: Mar. 23rd, 2020; accepted: Apr. 8th, 2020; published: Apr. 15th, 2020

ABSTRACT

Objective: To investigate whether monocyte to large platelet ratio (MLPR) is associated with pulmonary embolism (PE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A retrospective analysis was performed on patients with AECOPD who had undergone CTPA examination and suspected PE in the Affiliated Hospital of Qingdao University from January 2010 to June 2019 to compare the MLPR levels of the two groups of patients and plot the receiver operating characteristics (Receiver operating characteristics, ROC) curve to determine the critical value of MLPR. Results: This study included 232 patients in the AECOPD combined PE group and 470 patients in the AECOPD alone group. The MLPR (OR = 68.678) of the patients in the AECOPD combined PE group was higher than that in the AECOPD group alone, and was statistically significant (P < 0.05). It is 0.855 (95% CI 0.827 - 0.883), and when the MLPR value is >1.04%, it has the best diagnostic value for AECOPD combined with PE. At this time, the best diagnostic sensitivity is 94.8% and the diagnostic specificity is 75.7%. Conclusion: MLPR has important diagnostic value in patients with AECOPD and PE. It has high sensitivity and specificity, and has high clinical application value.

Keywords:Acute Exacerbation of Chronic Obstructive Pulmonary Disease, Pulmonary Embolism, Monocyte to Large Platelet Ratio

单核细胞–大血小板比率对AECOPD合并PE患者诊断价值

刘原源,程兆忠

青岛大学附属医院呼吸内科,山东 青岛

收稿日期:2020年3月23日;录用日期:2020年4月8日;发布日期:2020年4月15日

摘 要

目的:探究单核细胞–大血小板比率(Monocyte to large platelet ratio, MLPR)对于慢性阻塞性肺疾病急性加重(Acute exacerbation of chronic obstructive pulmonary disease, AECOPD)患者是否合并分肺栓塞(Pulmonary embolism, PE)。方法:回顾性分析2010年1月至2019年6月在青岛大学附属医院诊治的已行CTPA检查疑诊PE的AECOPD患者,比较两组患者MLPR水平,并绘制受试者操作特性(Receiver operating characteristics, ROC)曲线,确定MLPR的临界值。结果:该研究纳入AECOPD合并PE组患者232人,单纯AECOPD患者470人,AECOPD合并PE组患者MLPR (OR = 68.678)高于单纯AECOPD组,且有统计学意义(P < 0.05),MLPR的AUC为0.855 (95% CI 0.827~0.883),并当MLPR取值为>1.04%时,对AECOPD合并PE有最佳诊断价值,此时的最佳诊断灵敏度为94.8%,诊断特异度为75.7%。结论:MLPR在AECOPD合并PE患者中有重要的诊断价值,其兼具较高的灵敏度及特异度,具有很高的临床应用价值。

关键词 :慢性阻塞性肺疾病急性加重,肺栓塞,单核细胞–大血小板比率

Copyright © 2020 by author(s) and Hans Publishers Inc.

This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).

http://creativecommons.org/licenses/by/4.0/

1. 引言

PE是一种较为常见的高致死率的血栓栓塞性疾病 [1],而多项研究均表明,在慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)尤其AECOPD患者中其发病率更高 [2] [3]。

单纯AECOPD与AECOPD合并PE患者有相似的咳嗽、咯血、呼吸困难的临床表现,但常规实验室检查如血气分析、D二聚体等并不能明确诊断,现常用计算机断层扫描肺血管造影(Computed tomographic pulmonary angiography, CTPA)确诊PE,但该检查为有创检查,对于造影剂过敏、肾功能损害等患者并不适用,且费用较高。因此,开发一种简便、廉价的诊断工具协助AECOPD患者PE的诊断十分必要。

单核细胞作为组织因子的重要来源,在凝血级联反应中起到了至关重要的作用 [4]。且在AECOPD患者中,受到低氧及体内升高的CRP的刺激,单核细胞可增多并释放更多的组织因子促进凝血 [5] [6]。有研究表明,血小板的大小与其功能呈正相关 [7],且血小板的聚集似乎选择性涉及大血小板,这意味着当体内存在血栓时,大血小板聚集则是其主要来源 [8]。结合以上单核细胞及大血小板的作用相关研究,MLPR似乎可为评估AECOPD患者是否PE的良好指标。

2. 资料与方法

2.1. 一般资料

2010年1月至2019年6月经青岛大学附属医院医院诊治的AECOPD合并PE及单纯AECOPD患者,回顾性搜集分析其性别、年龄、既往病史及入院时心率、血常规、血气分析、CRP、PCT、D二聚体等临床资料,收集资料时已告知患者并征得患者知情同意。

两组患者纳入标准:1) 依据2019年慢性阻塞性肺疾病全球防治创议(GOLD) [9],符合慢阻肺诊断标准的患者[吸入支气管扩张剂后第1秒用力呼吸容积(FEV1)/用力肺活量(FVC) ≥ 70%]。2) 患者在短期内出现气促加重,痰量增加,痰变脓性三项中的两项或更多,并需改变COPD治疗期间常规用药。3) Wells评分或改良Geneva评分提示PE风险为中危或高危。4) 经CTPA检查后排除PE。5) 经CTPA检查后确诊合并PE。排除标准:1) 临床资料不完整。2) 既往2月内输血史。3) 患急性冠脉综合征、肺水肿、气胸及需要侵入性或非侵入性通气治疗的患者。4) 治疗剂量抗凝药应用史。5) 合并任何骨髓增生性疾病、骨髓纤维化、Glanzmann病,Bernard-Soulier综合征,怀疑弥散性血管内凝血患者。单纯AECOPD组纳入标准:符合以上纳入标准1)~4)条,并不符合排除标准中任何一条者。AECOPD合并PE组纳入标准:符合纳入标准1)~3)、5),并不符合排除标准中任何一条者。

2.2. 研究方法

对两组患者的临床资料进行对照分析。其中MLPR计算如下:MLPR = (单核细胞计数)/(大血小板计数) × 100% [10]。

2.3. 统计分析

采用SPSS22.0软件对数据进行统计描述和分析。符合正态分布的计量资料采用均数 ± 标准差( x ¯ ± s)描述,组间比较采用独立样本t检验。非正态分布的计量资料采用中位数(P50)、四分位数间距(P25,P75)描述,组间比较采用Mann-Whitney检验。分类资料采用频数(百分比)描述,组间比较采用Pearson χ2检验。P < 0.05为差异有统计学意义。对于有统计学意义的指标,计算其OR及95%置信区间并采用多因素Logistic回归分析AECOPD合并PE的独立影响因素。采用ROC曲线评价相关指标对AECOPD合并PE的诊断价值,并计算其对应的AUC进行分析并将其预测准确性与CTPA结果相比。

3. 结果

3.1. 一般资料分布

AECOPD合并PE及单纯AECOPD患者在性别、年龄、吸烟史、肥胖、合并恶性肿瘤、合并高血压、合并糖尿病、合并心脏病、合并慢性肾脏疾病、既往肺栓塞病史、既往心肌梗死病史方面差异无统计意义。而AECOPD合并PE组患者既往DVT病史者较单纯AECOPD明显增多且差异具有统计学差异) (表1表2)。

Table 1. Gender of patients with AECOPD alone and ACOPD combined with PE

表1. 单纯AECOPD及ACOPD合并PE患者性别

Table 2. Past medical history of patients with AECOPD alone and ACOPD with PE

表2. 单纯AECOPD及ACOPD合并PE患者既往病史

3.2. 临床指标

对共702例患者进行单因素分析,结果如下:AECOPD合并PE组的D二聚体、单核细胞计数、CRP、PDW、MPV、MLPR高于单纯AECOD组,差异统计学意义(P < 0.05)。AECOPD合并PE组的淋巴细胞计数、血小板、大血小板计数、PLR、大血小板/淋巴细胞比率低于单纯AECOD组,差异统计学意义(P < 0.05)。两组患者的年龄、心率、白细胞计数、PCT、PH、PaO2、SaO2、PaCO2、HCO3-、BE比较,差异无统计学意义(P > 0.05) (见表3)。

Table 3. Single factor analysis of clinical indicators of patients with AECOPD and ACOPD combined with PE

表3. 单纯AECOPD及ACOPD合并PE患者临床指标单因素分析结果

选取单因素分析有统计学意义指标进行多因素Logistic回归分析。结果显示,D二聚体(OR = 1.000)、CRP (OR = 1.309)、MPV (OR = 0.040)、PDW (OR = 3.330)、MLPR (OR = 80.680)、合并DVT (OR = 19.360)是AECOPD合并PE的危险因素,大血小板计数(OR = 0.909)是AECOPD合并PE的保护因素,有统计学意义(P < 0.05) (见表4)。

Table 4. Multivariate Logistic regression analysis of patients with AECOPD and PE

表4. AECOPD合并PE患者的多因素Logistic回归分析

使用SPSS,以AECOPD合并PE为状态变量,分别以MPV、PDW、MLPR、大血小板计数、CRP、D二聚体、既往DVT这7项指标为检验变量计算AUC,可见MLPR具有最佳诊断价值(表5),MLPR的AUC为0.855 (95%CI 0.827~0.883),诊断价值非常好,并当MLPR > 1.04%时,对AECOPD合并PE有最佳诊断价值,此时的最佳诊断灵敏度为94.8%,诊断特异度为75.7%,约登指数为0.705,其ROC曲线如下(图1),余指标均不能兼具较高的灵敏度、特异度,诊断效果较差。

Table 5. ROC curves analysis of risk factors

表5. 危险因素的诊断ROC曲线分析

4. 讨论

单因素分析中可见AECOPD合并PE患者中单核细胞计数明显升高,且具有统计学差异。多项研究表明 [5] [11] [12] [13] 循环单核细胞和巨噬细胞可能有助于特发性DVT的发病机理可能如下:1) PE患者的循环单核细胞和源自单核细胞的巨噬细胞M1趋化蛋白明显升高,同时伴有IL-6和TNF-α水平的轻微升高,均可刺激并上调内皮细胞介导的包括细胞间黏附分子-1 (Intercellular cell adhesion molecule-1, ICAM-1)和血管细胞粘附分子-1 (Vascular cell adhesion molecule 1, VCAM-1)在内的粘附分子表达,而黏附分子可以通过使白细胞粘附于内皮壁,引起血管病变,并增加了血小板积聚促进静脉血栓形成;2) 单核细胞在凝血级联反应起到至关重要的作用 [13]。单核细胞被认为是组织因子重要来源,而组织因子是凝血级联反应关键元素。

Figure 1. ROC curve of MLPR

图1. MLPR ROC曲线

将单核细胞和炎症与血栓生成联系在一起的另一个重要机制是血小板–单核细胞的串扰,它可以导致单核细胞–血小板聚集。血小板可以通过P选择素与单核细胞上的白细胞受体P选择素糖蛋白配体1 (Leukocyte receptor P-selectin glycoprotein ligand 1, PSGL-1)结合,但研究表明其与单核细胞结合更持久稳定 [14]。血小板的活化对单核细胞–血小板的聚集也尤为重要,Bournazos等人的研究表明 [15],活化的血小板可以促进单核细胞的促炎症反应,提高机体内多种炎症因子水平,进一步促进血栓形成。

而血小板的活化与功能与血小板体积的呈正相关,血小板的聚集速度与程度随其体积增加而增大。因为大血小板的密度更高,每个血小板及其每立方微米血小板体积的致密体数量更多,内含的乳酸脱氢酶的酶活性更高;并且随着凝血酶浓度的增加,血小板可摄取和释放更多的5-羟色胺。本研究中AECOPD合并PE组患者大血小板计数均明显降低,且具有统计学意义,考虑为AECOPD患者体内存在炎症反应,血小板活化,体积增大,但合并PE患者由于血小板参与血栓形成,故在外周血液中数量降低,而血小板聚集速度随其体积增大而增快,故大血小板计数降低更为明显。这也与既往研究结果相符。

5. 结论

综上所述,AECOPD合并PE患者较单纯AECOPD患者具有较高的单核细胞计数及较低的大血小板计数,故其MLPR较单纯AECOPD患者更高,它可能是协助判断AECOPD是否合并PE的简单、便宜、可靠工具,其兼具较高的灵敏度及特异性,有助于减少CTPA过度使用的程度,从而减少潜在并发症的风险,具有较高的临床效益。

文章引用

刘原源,程兆忠. 单核细胞–大血小板比率对AECOPD合并PE患者诊断价值
Diagnostic Value of Monocyte-Large Platelet Ratio in Patients with AECOPD and PE[J]. 临床医学进展, 2020, 10(04): 482-488. https://doi.org/10.12677/ACM.2020.104076

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