极重度替罗非班相关血小板减少症临床病例分析

Clinical case analysis of extremely severe tirofiban-induced thrombocytopenia

目的探讨极重度替罗非班相关血小板减少症(TIT)的发生情况及其临床特征。方法检索医院信息系统,统计2015年3月至2021年9月在临沂市人民医院住院期间使用替罗非班患者例数,收集用药后发生极重度TIT患者的病历进行回顾性分析。从病历中提取的数据包括患者性别、年龄、用药指征、合并症、替罗非班用药情况、合并用药情况、使用替罗非班前后血小板计数(PLT)、出现血小板减少时间、PLT最低值出现时间、TIT临床表现、干预和转归等。结果设定时段内使用过替罗非班的住院患者共10354例,其中20例(0.19%)发生极重度TIT。20例患者中男性16例,女性4例;年龄39~84岁,平均66岁,≥65岁者12例;用药指征为急性心肌梗死者8例,脑梗死5例,不稳定型心绞痛4例,冠状动脉旁路移植术后、短暂性脑缺血发作和支架植入术后各1例;合并高血压病者13例,糖尿病4例,脑梗死3例,美国纽约心脏病协会心力衰竭分级(NYHA)≥Ⅲ级者3例;替罗非班用药途径为静脉持续泵入,用药时间1~48 h;联用药物包括阿司匹林肠溶片、氯吡格雷片、替格瑞洛片、肝素、低分子肝素、阿替普酶和纤溶酶;5例在用药1~6 h出现畏寒、寒战等症状,7例在用药1~7 d出现口腔黏膜出血、鼻出血、牙龈出血、皮肤瘀斑、静脉穿刺处瘀斑、柏油样便或便血等症状,10例无临床症状。使用替罗非班至出现血小板减少和PLT最低值[(1~18)×10^(9)/L]的中位时间分别为12(6,20)h和18(12,22)h,13例患者出现血小板减少的时间与出现PLT最低值的时间一致。诊断极重度TIT后20例患者均停用替罗非班,给予糖皮质激素、人免疫球蛋白和/或输注血小板等治疗,18例在3~17 d(中位时间4 d)后PLT恢复至(100~258)×10^(9)/L;2例诊断后2、1 d分别出现柏油样便和便血,随后发生呼吸和心脏骤停并死亡。结论极重度TIT发生率低,起病急,可导致致命性出血事件,部分患者可无临床症状。停用替罗非班并予糖皮质激素和对症治疗后预后一般较好,但应警惕继发出血事件导致的不良后果。

Objective To investigate the occurrence and clinical characteristics of extremely severe tirofiban-induced thrombocytopenia(TIT).Methods Patients who used tirofiban during hospitali-zation in Linyi people′s Hospital from March 2015 to September 2021 was screened through the hospital information system.The medical records of patients with extremely severe TIT after medication were collected and analyzed retrospectively.The patient data extracted from the medical records included gender,age,medication indication,comorbidities,tirofiban application,combined drugs,platelet count(PLT)before and after tirofiban use,thrombocytopenia onset time from the application of tirofiban,the time to minimum value of PLT from medication,and the clinical manifestations,intervention,and prognosis of TIT,etc.Results A total of 10-354 inpatients who used tirofiban during the set period were entered,of which 20(0.19%)had extremely severe TIT.Among the 20 patients,16 were male and 4 were female,aged 39-84 years with an average age of 66 years,12 of which were≥65 years.The medication indications of tirofiban were acute myocardial infarction in 8 patients,cerebral infarction in 5 patients,unstable angina pectoris in 4 patients,and post-operation of coronary artery bypass grafting,transient ischemic attacks,and post-operation of coronary-stent implantation in 1 patient respectively.The comorbidities included hypertension in 13 patients,diabetes mellitus in 4 patients,cerebral infarction in 3 patients,and New York Heart Association(NYHA)greater than or equal to classⅢheart failure in 3 patients.Tirofiban was administered by continuous intravenous pumping for 1-48-hours.The combined drugs included aspirin enteric-coated tablets,clopidogrel tablets,ticagrelor tablets,heparin,low molecular weight heparin,alteplase,and plasmin.Five patients had symptoms of chills and shivers within 1-6 hours after treatment,7 had oral mucosal bleeding,epistaxis,gingival bleeding,skin ecchymosis,ecchymosis on venipuncture sites,tarry stool,or bloody stool within 1-7 days after treatment,and 10-had no clinical symptoms.The median time from tirofiban application to the onset of PLT decrease and to the minimum value of PLT[(1-18)×10^(9)/L]were 12(6,20)and 18(12,22)hours,respectively,and the 2 kinds of time above were consistent in 13 patients.Tirofiban was discontinued in all patients after the diagnosis of extremely severe TIT,and treatments with glucocorticoids,human immunoglobulin,and platelet infusion were given.PLT recovered to(100-258)×10^(9)/L after 3-17 days(median time 4 days)of treatments in 18 patients.The other 2 patients developed tarry stool and bloody stool 2 and 1 days after the diagnosis of TIT,respectively,followed by respiratory and cardiac arrest,and died.Conclusions Extremely severe TIT has low incidence but urgent onset,which can lead to fatal bleeding events,and some patients may have no clinical symptoms.The prognosis is generally good after tirofiban withdrawal and receiving glucocorticoids and symptomatic treatments.However,it should be alert to the adverse consequences caused by secondary bleeding events.