替加环素对患者凝血功能影响的临床回顾分析

发布时间：2019-02-13 15:31

【摘要】：背景：替加环素(Tigecycline)为首个应用于临床的甘氨酰环素类抗菌药物,抗菌谱广,不易产生耐药,对多重耐药(MDR)病原菌一直保持较高敏感度,是我国目前治疗复杂的多重耐药病原菌,尤其是碳青霉烯耐药革兰氏阴性杆菌重症感染的常用药物。随着替加环素临床应用越发广泛,对替加环素不良反应的认识也越发重要。根据2004-2009年FDA不良事件报告系统数据库,替加环素可查询的不良反应多为恶心、呕吐、胰腺炎、肝脏衰竭、低血糖等,缺少对患者凝血功能的的报告。近几年,国外共有两篇替加环素导致患者血浆纤维蛋白原降低的病例报道,而在临床工作中,我们也注意到部分患者在替加环素治疗期间出现明显的纤维蛋白原下降和凝血功能异常。但是,目前还缺乏替加环素对患者凝血功能影响的系统性临床研究。目的：评估替加环素治疗重症感染时对患者凝血功能的影响,为临床合理使用替加环素提供参考。方法：收集2012年4月至2014年12月期间收住于山东大学齐鲁医院并使用替加环素治疗72h以上的患者病例资料,进行回顾性临床分析。记录患者在接受替加环素治疗前、治疗期间及停药后的外周血纤维蛋白原(FIB)、凝血酶原时间(PT)、部分激活凝血酶原时间(APTT)、凝血酶时间(TT)和血小板(PLT),评估替加环素对患者凝血指标的影响。记录患者治疗期间的C反应蛋白(CRP)、体温、白细胞计数(WBC)、中性粒细胞比率(NEU%),以评估替加环素治疗期间的感染状态。比较患者用药前及用药7天以后的谷丙转氨酶(ALT)、血清总胆红素(TBIL)及血肌酐(Cr),以评估替加环素对肝肾功能的影响。记录患者治疗期间的血液成分输注情况及出血事件。使用SPSS22.0软件进行统计学分析处理。结果：共有151例患者符合入选标准。替加环素给药期间,患者血浆FIB水平呈明显下降趋势：与给药前相比,给药第2-3天、4-6天、7-10天及10天以上的平均FIB水平均明显降低(均P0.05)。替加环素停药后,患者FIB水平显著回升：与给药10天以上相比,停药第5-7天、7天以上的FIB水平明显升高(均P0.05)。PT、APTT和TT水平也随给药时间呈明显延长趋势,停药后逐渐缩短(均P0.05)。替加环素给药前后患者血小板水平变化不大,差异无统计学意义(P0.05)。替加环素给药后患者C反应蛋白和体温均明显下降(均P0.05),提示患者感染状态好转。给药前及给药7天后患者的谷丙转氨酶、血清总胆红素及血肌酐等指标的差异无统计学意义(均P0.05)。除外血液系统疾病患者,替加环素治疗期间患者输血率及输血量均高于ICU住院患者平均水平。结论：1.替加环素可导致患者凝血功能异常,主要表现为FIB下降和PT、APTT、TT延长,但对血小板无明显影响,停用后患者凝血功能可逐渐恢复。2.接受替加环素治疗的ICU患者输血率高于其他ICU患者,治疗期间应当注意监测患者凝血指标,警惕出血事件发生。3.替加环素治疗期间患者感染状态好转,肝肾功能无明显恶化,提示凝血异常与感染状态和肝肾功能等无关。
[Abstract]:Background: tigecycline is the first anti-bacterial drug which is applied to the clinical application of the anti-bacterial drugs, has wide antibacterial spectrum, is not easy to generate drug resistance, has high sensitivity to multiple drug-resistant (MDR) pathogenic bacteria, and is a complex multi-drug-resistant pathogenic bacteria at present in China, in particular to a common medicament for the severe infection of carbapenem-resistant Gram-negative bacilli. As the clinical application of tigecycline is more and more extensive, the understanding of the adverse reaction of tigecycline is also becoming more and more important. According to the FDA adverse event reporting system database for 2004-2009, the adverse reactions to which the tigecycline can be queried are nausea, vomiting, pancreatitis, liver failure, hypoglycaemia, etc., and lack of a report on the coagulation function of the patient. In recent years, two cases of tigecycline in foreign countries have led to a case-by-case report on the reduction of plasma fibrinogen in patients, and in clinical work, we also note that some of the patients had a marked decrease in fibrinogen and abnormal blood coagulation during the treatment of tigecycline. However, there is also a lack of systematic clinical studies on the effect of tigecycline on the coagulation function of patients. Objective: To evaluate the effect of tigecycline on the coagulation function of patients with severe infection and to provide reference for the rational use of tigecycline. Methods: From April 2012 to December 2014, a retrospective clinical analysis was carried out in Qilu Hospital of Shandong University and using tigecycline for more than 72h. The patients were recorded in the peripheral blood fibrinogen (FIB), prothrombin time (PT), partial activation of prothrombin time (APTT), thrombin time (TT), and platelets (PLT) after treatment, during and after treatment with tigecycline, The effect of tigecycline on the coagulation index of patients was assessed. The C-reactive protein (CRP), body temperature, white blood cell count (WBC), and neutrophil ratio (NEU%) during the patient's treatment were recorded to assess the status of infection during the treatment of tigecycline. The effect of tigecycline on the liver and kidney function was assessed by comparing the alanine aminotransferase (ALT), serum total bilirubin (TBIL) and serum myoglobin (Cr) before and after the administration of the patient. Record the blood component infusion and the bleeding event during the patient's treatment. Statistical analysis was performed using the SPSS10.0 software. Results: A total of 151 patients met the inclusion criteria. The plasma FIB level in the patients decreased significantly during the administration of tigecycline: the mean FIB levels were significantly lower in the day 2-3, 4-6, 7-10, and 10 days prior to administration (P0.05). The FIB level of the patients recovered significantly after the discontinuation of tigecycline: compared with that of the administration for more than 10 days, the level of FIB in the 5-7 and more days of the drug withdrawal was significantly higher (all P0.05). The levels of PT, APTT and TT were also significantly prolonged with the time of administration, and were gradually shortened after drug withdrawal (P <0.05). There was no significant difference in the level of platelet in patients before and after administration of tigecycline (P0.05). The C-reactive protein and body temperature of the patients were significantly decreased after the administration of tigecycline (both P0.05). There was no significant difference in the indexes of alanine aminotransferase, total bilirubin and serum myoglobin in the patients before and after administration for 7 days (P0.05). The rate of blood transfusion and the amount of blood transfusion during the treatment of tigecycline were higher than those in the ICU, except for patients with blood system diseases. Conclusion: 1. tigecycline could lead to an abnormality in the coagulation function of the patient, mainly by FIB and PT, APTT and TT, but no significant effect on the platelets, and the coagulation function of the patients can be gradually recovered after being stopped. The rate of blood transfusion in the ICU patients treated with tigecycline was higher than that of other ICU patients. During the treatment period, attention should be paid to monitoring the coagulation index of the patient and to be alert to the occurrence of bleeding events. During the treatment of tigecycline, the infection status of the patients was improved, and the function of the liver and kidney was not significantly deteriorated. It was suggested that the coagulation abnormality was not related to the infection status and the function of the liver and kidney.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R969

【相似文献】