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替加环素致严重肾功能不全患者凝血功能异常的回顾性分析
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          沈 莉 ,方 伟 ,张 尧,潘 洋,周泽伟(重庆大学附属三峡医院药学部,重庆 404000)
          中图分类号  R969.3      文献标志码  A      文章编号  1001-0408(2023)22-2766-04
          DOI  10.6039/j.issn.1001-0408.2023.22.14

          摘   要  目的  分析替加环素对严重肾功能不全患者凝血功能的影响,为临床安全用药提供参考。方法  回顾性分析2021年1月
          至2022年10月我院肾病学科收治的使用替加环素治疗的严重肾功能不全合并感染患者的临床资料。比较患者用药前3 d,用药
          1~5、6~10、11~15、16~20 d后及停药5 d后和/或对症处理后的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、国际标准
          化比值(INR)、血小板(PLT)、纤维蛋白原(FIB)水平。结果  共纳入 14 例患者,有 9 例患者发生了凝血功能异常,发生率为
          64.29%。与用药前3 d比较,患者用药6~10、11~15 d后FIB水平及用药1~5、6~10、11~15 d后PLT水平均显著降低,用药1~
          5、6~10 d后PT及用药1~5、6~10、11~15 d后APTT均显著延长,用药1~5、6~10 d后INR均显著升高(P<0.05);而用药16~
          20 d及停药5 d后和/或对症处理后FIB、PT、INR、APTT、PLT与用药前3 d比较,差异均无统计学意义(P>0.05)。结论  严重肾功
          能不全患者需谨慎使用替加环素;替加环素可导致患者的PT、APTT延长,INR升高,PLT、FIB降低;用药疗程>14 d时,临床需对
          患者凝血指标进行动态监测,以降低不良反应的发生风险。
          关键词  替加环素;凝血功能异常;肾功能不全;不良反应

          Retrospective analysis of coagulopathy in patients with severe renal insufficiency caused by tigecycline
          SHEN Li,FANG Wei,ZHANG Yao,PAN Yang,ZHOU Zewei(Dept.  of  Pharmacy,  Three  Gorges  Hospital
          Affiliated to Chongqing University, Chongqing 404000, China)

          ABSTRACT    OBJECTIVE  To  analyze  the  effects  of  tigecycline  on  coagulation  function  in  patients  with  severe  renal
          insufficiency,  and  to  provide  a  reference  for  safe  clinical  drug  use.  METHODS  Retrospective  analysis  was  performed  for  the
          clinical  data  of  patients  with  severe  renal  dysfunction  complicated  with  infection  receiving  tigecycline  admitted  to  nephrology
          department  of  our  hospital  from  January  2021  to  October  2022.  The  levels  of  prothrombin  time (PT),  activated  partial
          thromboplastin  time (APTT),  international  normalized  ratio (INR),  platelet (PLT)  and  fibrinogen (FIB)  were  compared  3  days
          before  medication,  with  1-5,  6-10,  11-15  and  16-20  days  after  medication,  5  days  after  withdrawal  and/or  after  symptomatic
          treatment.  RESULTS  Finally,  14  patients  were  included,  and  9  patients  developed  coagulopathy,  with  an  incidence  of  64.29%.
          Compared with 3 days after medication, the levels of FIB at 6-10 and 11-15 days after medication, and PLT at 1-5 , 6-10 and 11-
          15 days after medication were decreased significantly, while the levels of PT at 1-5 and 6-10 days after medication, APTT at 1-5,
          6-10  and  11-15  days  after  medication  were  significantly  prolonged,  and  INR  increased  significantly  at  1-5  and  6-10  days  after
          medication (P<0.05). Compared with 3 days before medication, there were no statistically significant changes in FIB, PT, INR,
          APTT  and  PLT  at  16-20  days  after  medication  and  5  days  after  withdrawal  and/or  symptomatic  treatment(P>0.05).
          CONCLUSIONS Patients with severe renal insufficiency should be cautious with tigecycline, which can lead to prolonged PT and
          APTT,  increased  INR,  and  decreased  PLT  and  FIB.  If  medication  time  is  over  14  days,  dynamic  monitoring  of  coagulation
          function indicators is recommended to reduce the risk of adverse reactions.
          KEYWORDS     tigecycline; coagulopathy; renal insufficiency; adverse reaction



              替加环素作为新一代甘氨酰四环素类广谱抗菌药                           分凝血活酶时间(activated partial thromboplastin time,
          物,对常见致病菌或多重耐药菌具有良好的抗菌活性,                            APTT)延长、凝血酶原时间(prothrombin time,PT)延长、
          在治疗成人复杂性腹腔感染、皮肤软组织感染和社区获                            国际标准化比值(international normalized ratio,INR)升
                                                                                       [2]
                                  [1]
          得性肺炎等方面的效果较好 。替加环素常见的不良反                            高、血小板(platelet,PLT)减少 。近年来,有文献报道了
          应有恶心、呕吐、肝功能异常、皮疹、凝血功能异常等,其                          替加环素对凝血功能的影响,凝血功能异常可能会导致
          中该药说明书提及的凝血系统不良反应主要有活化部                             患者原有疾病病情加重、治疗费用增加、住院时间延长
                                                                                                 [2]
                                                              及预后不佳等,最终影响患者的治疗结局 。
              Δ 基金项目 重庆市首批临床药学重点专科建设项目(No.渝卫办
                                                                  严重肾功能不全患者因接受持续性肾脏代替治疗
          发〔2020〕68号)                                         和免疫缺陷、营养不良、留置导管、长期/反复住院史等原
             * 第一作者 主 管 药 师 。 研 究 方 向 :临 床 药 学 。 E-mail:
                                                                                         [3]
                                                              因,使得感染耐药菌的风险较高 ,常需使用替加环素治
          308396782@qq.com
              # 通信作者 副主任药师,博士。研究方向:临床药学。E-mail:               疗。有研究认为,严重肾功能不全患者感染时应尽量避
          56127449@qq.com                                     免使用肾毒性抗菌药物,可选用经肝胆系统排泄的药

          · 2766 ·    China Pharmacy  2023 Vol. 34  No. 22                            中国药房  2023年第34卷第22期
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