住院患者使用利奈唑胺致相关性血小板减少症的危险因素分析

中国药物警戒 ›› 2012, Vol. 9 ›› Issue (2): 71-76.

住院患者使用利奈唑胺致相关性血小板减少症的危险因素分析

陈超，郭代红^*，曹秀堂，蔡云，王芝林²，徐元杰，朱曼，马亮，赵鹏芝

1 解放军总医院a药品保障中心，b统计科，北京100853；
2 沈阳药科大学，辽宁沈阳 110033

收稿日期:2011-09-19 出版日期:2012-02-10 发布日期:2015-08-10
通讯作者: 郭代红,女,硕士,主任药师,硕士生导师。E-mail:guodh301@yahoo.com.cn
作者简介:陈超，女，学士，主管药师，临床药学。
基金资助:
解放军总医院科技创新苗圃基金项目（10KMM41）

Analysis on the Risk Factors Associated with the Development of Thrombocytopenia in Patients Who Received Linezolid Therapy

CHEN Chao, GUO Dai-hong^*, CAO Xiu-tang, CAI Yun, WANG Zhi-lin², XU Yuan-jie, ZHU Man, MA Liang, ZHAO Peng-zhi

1 aDepartment of Pharmacy, 1bDepartment of Statistics, the PLA General of Hospital, Beijing 100853, China;
2 Shenyang Pharmaceutical University, Liaoning Shenyang 110033, China

Received:2011-09-19 Online:2012-02-10 Published:2015-08-10

摘要/Abstract

摘要： 目的研究住院患者使用利奈唑胺致血小板减少的发生率及危险因素。方法采用回顾性横断面研究，以解放军总医院2011年1月至2011年5月间使用利奈唑胺的住院患者为研究对象，通过医院信息系统记录患者一般资料、病生理情况、用药情况并动态监测血小板计数变化。定义血小板减少症为低于正常值下限（即血小板计数<100×109/L），并根据排除标准控制混杂因素，对纳入病例使用利奈唑胺致血小板减少症的观察指标进行逐步逻辑回归筛选危险因素，并绘制ROC曲线预测发生特征。结果获得用药病例345例，按入排标准纳入有效病例208例，其中男性129（62.02%）例，女性79（37.98%）例，平均年龄为62.67±18.66（16~98）a，用药时间平均为9.68±6.07（3~39）天。使用利奈唑胺致相关性血小板减少症的有59例（28.37%），发生血小板低于正常值或基础值的25％的有106例（50.96%），其中有20人（9.62%）发生了Ⅲ度和Ⅳ度血小板下降，需要输血或输注血小板。单因素分析显示年龄、肌酐清除率、基础血小板值、总胆红素、血清白蛋白对血小板减少症的影响具有统计学意义，逐步逻辑回归多因素分析显示基础血小板值和年龄与血小板减少症密切相关。绘制血ROC曲线Youden指数最大时（0.3855），曲线下面积为0.739时，对应切点的敏感度为62.71%，特异度为75.84%。结论基础血小板值、年龄是利奈唑胺致相关性血小板减少症的独立危险因素，对基础血小板值≤204×109/L、年龄≥82岁的患者，容易发生明显血小板减少症甚至出血风险，应加强血常规监测频率。低肌酐清除率、低血清白蛋白水平也是发生血小板减少的重要危险因素，提示利奈唑胺致相关性血小板减少症呈浓度依赖性，并与免疫机制相关。此外，可尝试使用ROC曲线筛选预测利奈唑胺相关性血小板减少的风险特征，并在易感人群中调整合适剂量以兼顾有效性和安全性。

关键词: 利奈唑胺, 血小板减少, 危险因素, 肾功能不全, 基础血小板值, ROC曲线, 药品不不良反应

Abstract: Objective This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy and to clarify the reasons and incidence of this adverse reaction. MethodsThis was a restrospective study of patients treated with linezolid by the oral or parenteral route,between January 2011 and May 2011. Data were extracted from the electronic medical records obtained from hospital information system.Thrombocytopenia was defined as a final platelet count of <100×109/L. Risk factors associated with thrombocytopenia in patients who received linezolid therapy were identified via logistic regression analysis,and to predict clinical feature via ROC curves. ResultsIn total, 208 patients(129 men and 79 women; mean[SD]age, 62.67[18.66]years[range,16-98 years]) were included in the study.The mean duration of linezolid therapy was 9.68[6.07]days,with a range of 3 to 39 days.Thrombocytopenia occurred in 59 patients(28.37%), defined as a decrease in platelet count of ≥25% from the baseline occurred in 106 patients(50.96%). Among the patients, 20 patients(9.62%) developed severe thrombocytopenia, requiring platelet transfusion. In univariate analysis, age, lowered creatinine clearance,serum albumin , low baseline platelet count, total bilirubin were significant factors for thrombocytopenia associated with linezolid therapy; however, in multivariate analysis, only age ,baseline platelet count were significant risk factors for thrombocytopenia associated with linezolid therapy. Draw ROC curves maximum, the curve Youden index for 0.739, corresponding area under the sensitivity degrees for 62.71%, specific degrees for 75.84%. ConclusionBaseline platelet count≤204×109/L, age≥82 years were independent risk factors associated with thrombocytopenia in patients who received linezolid therapy and the incidence may increase. Several factors may influence the occurrence of linezolid-induced thrombocytopenia. Further studys are necessary to determine which at-risk patients are candidates for concentation adjustment of linezolid. Furthermore,we can calculate the area under ROC curves to predict these cut off values for risk factors.

Key words: linezolid, thrombocytopenia, risk factor, renal insufficiency, baseline platelet count, ROC curves, adverse drug reaction

陈超，郭代红，曹秀堂，蔡云，王芝林，徐元杰，朱曼，马亮，赵鹏芝. 住院患者使用利奈唑胺致相关性血小板减少症的危险因素分析[J]. 中国药物警戒, 2012, 9(2): 71-76.

CHEN Chao, GUO Dai-hong, CAO Xiu-tang, CAI Yun, WANG Zhi-lin, XU Yuan-jie, ZHU Man, MA Liang, ZHAO Peng-zhi. Analysis on the Risk Factors Associated with the Development of Thrombocytopenia in Patients Who Received Linezolid Therapy[J]. Chinese Journal of Pharmacovigilance, 2012, 9(2): 71-76.

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