应用硫唑嘌呤治疗炎症性肠病致白细胞减少症的相关因素分析Δ  

Analysis of Related Factors of Leukopenia Induced by Azathioprine in the Treatment of Inflammatory Bowel Disease

作　　者：汪燕燕[1] 苏涌[1] 杨春兰[1] 夏泉[1] 许杜娟[1] 胡乃中[2] 

机构地区：[1]安徽医科大学第一附属医院药剂科,合肥230022 [2]安徽医科大学第一附属医院消化内科,合肥230022

出　　处：《中国药房》2016年第17期2348-2351,共4页China Pharmacy

基　　金：安徽省自然科学基金青年项目(No.1508085QH166)

摘　　要：目的:探讨硫唑嘌呤(AZA)治疗炎症性肠病(IBD)致白细胞减少症的临床相关因素。方法:收集我院2013年1月-2015年3月114例IBD患者的临床资料,采用高效液相色谱法测定其红细胞内AZA代谢物6-硫鸟嘌呤核苷酸(6-TGNs)的稳态浓度,考察患者性别、年龄、疾病种类、AZA日剂量、6-TGNs血药浓度与AZA致白细胞减少症的相关性,并采用受试者工作特征(ROC)曲线预测白细胞减少的最佳临界值。结果:114例IBD患者中,发生白细胞减少症的患者有40例(35.1%)。不同年龄、性别、疾病种类及AZA日剂量患者间发生白细胞减少症的比例比较,差异均无统计学意义(P>0.05)。不同6-TGNs血药浓度患者发生白细胞减少症的比例比较,差异有统计学意义(P<0.05)。发生白细胞减少症的患者体内6-TGNs平均血药浓度[(407.82±262.88)pmol/(8×108)RBC]高于白细胞水平正常的患者[(275.85±118.37)pmol/(8×108)RBC],差异有统计学意义(P<0.05)。ROC曲线预测其白细胞减少症发生的最佳临界值为6-TGNs血药浓度>291.04 pmol/(8×108)RBC。结论:AZA致白细胞减少症的发生可能与IBD患者红细胞内6-TGNs的浓度相关,且高浓度6-TGNs是其发生白细胞减少症的危险因素;医师可结合患者血常规数据与红细胞内6-TGNs浓度的检测结果,针对IBD患者开展AZA个体化治疗,以减少白细胞减少症的发生。OBJECTIVE：To explore the clinical related factors of leucopenia induced by azathioprine in the treatment of inflammatory bowel disease（IBD）. METHODS：Clinical information of 114 IBD patients were collected from our hospital during Jan.2013-Mar. 2015. Steady concentration of AZA metabolite 6-thioguanine（6-TGNs）in red blood cell was determined by HPLC. The correlation of patient＇s gender,age,diseases,AZA daily dose and blood concentration of 6-TGNs with leucopenia induced by AZA were investigated. The optimal critical value of leucopenia could be predicted with ROC curves. RESULTS：Among 114 IBD patients,40 patients suffered from leucopenia（35.1%）. There was no statistical significance in the proportion of leucopenia among patients with different age,gender,diseases and AZA daily dose（P〉0.05）. There was statistical significance in the proportion of leucopenia among patients with different concentrations of 6-TGNs（P〈0.05）. Mean blood concentration of 6-TGNs in leukopenia patients [（407.82±262.88）pmol/（8×108）RBC] was higher than patients with normal leukocyte level [（275.85±118.37）pmol/（8×108）RBC],with statistical significance（P〈0.05）. ROC curve predicted that the optimal critical value of leucopenia was blood concentration of 6-TGNs〉291.04 pmol/（8×108）RBC. CONCLUSIONS：AZA induced leucopenia may be related to the concentration of 6-TGNs in red blood cell of IBD patients,and high concentration of 6-TGNs is risk factors of leucopenia. Clinicians can provide AZA individual treatment for IBD patient to reduce the occurrence of leucopenia according to routine blood test and the concentration of 6-TGNs.

关 键 词：硫唑嘌呤 炎症性肠病 白细胞减少症 6-硫鸟嘌呤核苷酸 血药浓度 

分 类 号：R979.5[医药卫生—药品] R574.53[医药卫生—药学]