红细胞分布宽度对急性胰腺炎严重程度和预后评估的价值

薛力玮， 刘 颖

1.桂林医学院，广西 桂林 541001； 2．桂林医学院第二附属医院消化科

红细胞分布宽度对急性胰腺炎严重程度和预后评估的价值

薛力玮1， 刘 颖2

1.桂林医学院，广西 桂林 541001； 2．桂林医学院第二附属医院消化科

目的探讨红细胞分布宽度(red blood cell distribution width, RDW)水平及入院后其动态变化对急性胰腺炎(acutepancreatitis, AP)病情预后的评估价值。方法选择2010年1月至2017年6月在桂林医学院附属医院收治的AP患者120例，设轻症组(MAP，43例)、中-重症组(MSAP，32例)及重症组(SAP，45例)；根据是否诊断为SAP组，分为非SAP组(75例)和SAP组(45例)；再将SAP组分为生存组(25例)、死亡组(20例)；对照组为健康体检者(30名)。收集患者入院时RDW、入院48 h后RDW、对照组RDW及其他相关临床资料，比较各组间RDW的差异、RDW的动态变化、RDW与APACHEⅡ评分、Ranson评分的相关性，利用受试者工作特征曲线(ROC)并确定曲线下面积(AUC)来分析RDW对AP的严重程度和预后的价值。结果SAP组入院时RDW及入院48 h后RDW均明显高于其他三组(P<0.001)；SAP组及MSAP组中，入院48 h后RDW与入院时RDW变化不大(P>0.05)；在多因素 Logistic 回归分析中，入院时RDW、APACHEⅡ评分、Ranson评分等指标均为SAP诊断及院内死亡的独立危险因素(P<0.05)；入院时RDW对诊断SAP的预测价值ROC曲线分析显示，RDWAUC为0.953(95%CI：0.899～0.983，P<0.001)；根据约登指数计算出入院时RDW最佳临界值为13.9%，敏感度为95.56%，特异度为81.33%；入院时RDW对SAP院内死亡的预测价值ROC曲线分析显示，RDWAUC为0.849(95%CI: 0.711～0.938，P<0.001)；根据约登指数计算出入院时RDW最佳临界值为16.2%，敏感度为70.00%，特异度为92.00%。结论RDW可预测AP的严重程度和预后，同时RDW的动态变化对AP的病情可能具有较好的预测价值。

红细胞分布宽度；急性胰腺炎；预后评估

急性胰腺炎(acute pancreatitis,AP)按病情严重程度，可分为轻症胰腺炎(mild acute pancreatitis, MAP)、中-重症胰腺炎(moderately severe acute pancreatitis, MSAP)、重症胰腺炎(severe acute pancreatitis, SAP)[1]。大多数AP常呈自限性，预后良好，但在SAP中，由于胰腺酶进入血液和随后造成对各个器官的损伤，在器官损伤后，会释放大量炎症介质和细胞因子，疾病早期即可引起系统性并发症，如全身炎症反应综合征(systemic inflammatory response syndrome, SIRS)和多器官功能障碍综合征(multiple organ dysfunction syndrome, MODS)，严重AP的死亡率为36%～50%[2]。因此, 在入院后24～48 h内评估AP患者严重程度和预后对AP的早期治疗非常重要。

红细胞分布宽度(red blood cell distribution width, RDW)可反映红细胞的异质性。目前许多研究[3-7]已证实，RDW在各种疾病中可作为一个独立、强大的预后及并发症的预测指标，如心血管疾病、脑卒中、呼吸系统疾病及2型糖尿病。enol等[8]第一次证明了RDW是AP死亡的独立危险因素之一，但其机制尚不明确。本研究通过分析AP患者早期RDW 水平与RDW 动态变化，评估RDW对AP严重程度和预后评估的价值，并探讨其机制。

1 资料与方法

1.1一般资料选择2010年1月至2017年6月在桂林医学院附属医院收治AP患者120例，研究对象符合中华医学会外科学分会胰腺外科学组《急性胰腺炎诊治指南》(2014年)的诊断标准[1]；按病情严重程度分为MAP组(43例)、MSAP组(32例)、SAP 组(45例)；根据是否诊断为SAP组，分为非SAP组(75例)和SAP组(45例)；再将SAP组分为生存组(25例)、死亡组(20例)；120例患者中，男82例、女38例，年龄(53.83±16.95)岁(21～89岁)；对照组为健康体检者30名，男19名、女11名，年龄(46.70±16.43)岁(22～74岁)。

1.2方法收集患者入院时RDW、入院48 h后RDW、对照组RDW及其他相关临床资料，统计SAP患者住院期间病死率。

2 结果

2.1入院时RDW比较120例AP患者入院时RDW明显高于对照组；MSAP组入院时RDW明显高于MAP组；SAP组入院时RDW明显高于MSAP组；但MAP组入院时RDW值与对照组的RDW值比较，差异无统计学意义(P>0.05，见表1)。

2.2入院48h后RDW动态变化情况MAP组中入院48 h后RDW明显低于入院时RDW(P<0.001)；MSAP、SAP组中入院48 h后RDW与入院时RDW比较，差异无统计学意义(P>0.05，见表1)。

表1 入院时与入院48 h后各组RDW值比较Tab 1 Comparison of RDW values at the time of admission and 48 hours after admission (±s)

注：与SAP组相比，*P<0.05;与MSAP组相比，#P<0.05。

2.3不同性别、病因AP患者RDW比较MAP组、MSAP组和SAP组内不同性别、病因入院时RDW比较，差异无统计学意义(P>0.05)；MAP组、MSAP组和SAP组内不同性别、病因入院48 h后RDW比较，差异无统计学意义(P>0.05，见表2)。

2.4RDW与APACHEⅡ评分、Ranson评分的相关性入院时RDW与APACHE Ⅱ评分、Ranson评分均存在良好的相关性，相关系数r值分别为0.778、0.678；入院48 h后RDW与APACHE Ⅱ评分、Ranson评分均存在良好相关性，相关系数r值分别为0.794、0.716。

2.5SAP组和非SAP组中临床资料比较年龄、入院时RDW、APACHE Ⅱ评分、Ranson评分在两组间比较，差异均有统计学意义(P<0.001，见表3)。Logistic 回归多因素分析显示：入院时RDW、APACHE Ⅱ评分、Ranson评分均为诊断SAP的独立危险因素(P<0.05)；在对诊断SAP预测价值ROC曲线分析显示，RDWAUC为0.953(95%CI: 0.899～0.983，P<0.001)；根据约登指数计算出入院时RDW最佳临界值为13.9%，灵敏度为95.56%，特异度为81.33%(见图1)；APACHE Ⅱ评分AUC为0.932 (95%CI: 0.871～0.970，P<0.001)；Ranson评分AUC为0.898 (95%CI: 0.830～0.946，P<0.001)。

2.6生存组和死亡组中临床资料比较入院时RDW、APACHE Ⅱ评分、Ranson评分在两组间比较，差异均有统计学意义(P<0.001，见表4)。Logistic回归多因素分析显示：入院时RDW、APACHE Ⅱ评分、Ranson评分均为SAP院内死亡的独立危险因素(P<0.05)；在对SAP院内死亡预测价值ROC曲线分析显示，RDWAUC为0.849(95%CI: 0.711～0.938，P<0.001);根据约登指数计算出入院时RDW最佳临界值为16.2%，灵敏度为70.00%，特异度为92.00%(见图2)；APACHE Ⅱ评分AUC为0.945(95%CI: 0.833～0.991，P<0.001)；Ranson评分AUC为0.888(95%CI: 0.758～0.962，P<0.001)。

表2 不同性别、病因AP患者RDW比较Tab 2 Comparison of RDW of AP patients between different gender and pathogenesis (±s)

表3 SAP组与非SAP组中一般临床资料比较Tab 3 Comparison of clinical characteristics between SAP group and non-SAP group (±s)

表4 生存组与死亡组中一般临床资料比较Tab 4 Comparison of clinical characteristics between survival group and death group (±s)

图1 RDW对SAP诊断预测价值的ROC曲线；图2 RDW对SAP院内死亡预测价值的ROC曲线Fig 1 ROC curve of RDW to predict the diagnosis of SAP; Fig 2 ROC curve of RDW to predict the hospital death of SAP

3 讨论

AP既包括胰腺局部炎症病变，也包括全身病理损伤。约20%的患者为SAP，常并发 MODS或感染而死亡[2]。目前Ranson评分仍然是评估AP病情严重程度的最常用的评分系统，但这个评分系统需要在入院后48 h来完成评估，其余的如APACHEⅡ评分、BISAP评分、MCTSI评分涉及许多测试，而且操作复杂，所以对临床实践并不方便；而在实验室检查中，肌酐、尿素氮特异性和灵敏性都有一定的局限性[9]；C反应蛋白(CRP)水平具有较高的灵敏性和阳性预测值，但CRP水平无法预测AP病情严重程度[10-11]；降钙素原(PCT)联合其他炎症指标，如白细胞介素-6(IL-6)，可预测AP炎症严重程度[12]，乙酰胆碱酯酶(AChE)对评估AP病情严重程度也具有较强的灵敏性和特异性[13]，但都不在临床常规检测范围内；白细胞介素-8(IL-8)、尿胰蛋白酶原激活肽(uTAP)、肿瘤坏死因子(TNF-α)目前还没有在临床上应用[9]。而RDW可反映全身系统的炎症反应，多项研究[8-9]证明，高水平RDW是对SAP患者死亡率的独立预测因子。

本研究发现，SAP组入院时RDW及入院48 h后RDW均明显高于MAP及MSAP组，在多因素 Logistic回归分析中RDW、APACHEⅡ评分、Ranson评分等指标均为SAP诊断及院内死亡的独立危险因素，通过ROC曲线分析，RDW对AP严重程度及预后的灵敏性及特异性均较强。而在SAP组及SMAP组中，入院48 h后RDW与入院时RDW变化不大，考虑与AP局部或全身并发症及器官功能衰竭有关，这也提示了RDW的动态变化可能对AP严重程度及预后有预测价值。

据报道[8]，RDW的变化与疾病的炎症状态有关，这也许可以解释为什么更高水平RDW值的AP患者病情更重、死亡率更高。炎性因子和氧化应激在AP的发病和进展中起至关重要的作用。胰腺腺泡细胞的损伤在AP早期导致局部炎症反应，之后腺泡细胞凋亡或坏死可导致SIRS及MODS[14]。若红细胞生成时缺乏铁、维生素B12、叶酸等造血原料时，相应的RDW就会升高[15]。炎症影响骨髓中红细胞前体和铁代谢，同时炎性细胞因子可破坏红细胞细胞膜，抑制其成熟，让更新、更大的网织红细胞进入循环， 从而使RDW升高[16]。炎症可改变红细胞膜糖蛋白和膜离子通道，使得红细胞形态发生变化，导致红细胞大小异质性增加[17-18]。而氧化应激可通过破坏核酸、蛋白及脂质从而降低红细胞存活率并让更多未成熟红细胞进入血液循环[19]。此外，SAP常因全身血容量下降导致肾前性的急性肾损伤，同时长时间肠外营养及应激状态可导致贫血，从而使RDW升高[20]。因此，RDW值反映了AP的炎症状态,可用于预测AP的严重程度和预后。

综上所述,RDW可预测AP的严重程度和预后，初步解释了其存在的机制，同时RDW的动态变化对AP的病情也可能具有较好的预测价值，但本研究属于回顾性分析, 存在样本相对偏少,且未对AP患者出院后进行随访，无法了解出院后RDW动态变化情况的问题，对研究结果难免造成偏差。此外，还需进一步探究AP中RDW升高的具体机制。

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(责任编辑：李 健)

Valueofredbloodcelldistributionwidthinassessingtheseverityandprognosticevaluationofacutepancreatitis

XUE Liwei1, LIU Ying2

1.Guilin Medical University, Guilin 541001; 2.Department of Gastroenterology, the Second Affiliated Hospital of Guilin Medical University, China

ObjectiveTo explore the value of red blood cell distribution width (RDW) and its dynamic changes after admission in assessing the severity and prognostic evaluation of acute pancreatitis (AP).MethodsOne hundred and twenty cases of AP patients including 43 cases of mild acute pancreatitis (MAP), 32 cases of moderate severe acute pancreatitis (MSAP) and 45 cases of severe acute pancreatitis (SAP) from Jan. 2010 to Jun. 2017 in the Affiliated Hospital of Guilin Medical University were selected. According to the diagnostis of SAP or not， patients were divided into non-SAP group (75 cases) and SAP group (45 cases). Patients in SAP group were divided into survival group (25 cases) and death group (20 cases)， 30 healthy volunteers were selected as the control group. RDW of patients was collected at the time of admission and 48 hours after admission to hospital, as well as the RDW of the control group and other relevant clinical data were collected. The difference value of RDW in each group, the dynamic changes of the RDW and the correlation of RDW with APACHE Ⅱ score, Ranson score were compared. The value of RDW to the severity and prognosis of AP were analyzed by theROCcurve and area under curve (AUC).ResultsThe RDW of SAP group at the time of admission and 48 hours after admission to hospital were significantly higher than those in the other three groups (P<0.001). In the SAP group and MSAP group, the RDW at the time of admission was not significantly changed after 48 hours in hospital (P>0.05). In a multiariable Logistic regression analysis, RDW, APACHE Ⅱ score and Ranson score indexes at the time of admission were all independent risk factors for SAP diagnosis and hospital death (P<0.05). TheROCcurve analysis of the prediction value of SAP in admission showed that the RDWAUCwas 0.953 (95%CI: 0.899-0.983,P<0.001). According to the Youden index, the optimal critical value of RDW when admission was 13.9 % and the sensitivity was 95.56 % and the specificity was 81.33 %. RDW on admission to hospital to prognosis of death in the hospital in SAP group ofROCcurve analysis showed that RDWAUCwas 0.849 (95%CI: 0.711-0.938,P<0.001). According to the Youden index, the optimal critical value of RDW when admission was 16.2% and the sensitivity was 70.00% and the specificity was 92.00%.ConclusionRDW can predict the severity and prognosis of AP, and the dynamic change of RDW may have important value to predict the condition of it.

Red blood cell distribution width; Acute pancreatitis; Prognostic evaluation

10.3969/j.issn.1006-5709.2017.11.026

国家自然科学基金(81660097)

薛力玮，在读硕士研究生，研究方向：消化系统疾病。E-mail: xueliwei0528@126.com

刘颖，博士，副主任医师，副教授，研究方向：胃肠动力。E-mail: liuy1009@sina.com

R576

A

1006-5709(2017)11-1301-04

2017-07-13