甲氨蝶呤治疗异位妊娠致全血细胞减少临床及文献病例分析

Clinical and literature case analysis on pancytopenia caused by methotrexate in treatment for patients with ectopic pregnancy

目的探讨甲氨蝶呤(MTX)治疗异位妊娠致全血细胞减少的临床特点。方法报道中日友好医院收治的1例MTX致异位妊娠患者全血细胞减少的诊治经过,并对该例以及检索中国知网、万方、维普和PubMed数据库(截至2020年6月30日)收集到的相关病例主要临床特征进行汇总分析,并比较死亡患者和存活患者MTX总剂量、首次应用MTX至全血细胞减少发生时间、白细胞计数(WBC)、血红蛋白(Hb)和血小板计数(PLT)最低值的差异。结果纳入分析的患者共18例,年龄20~41岁,平均30岁;其中2例为慢性肾脏病肾透析患者。首次应用MTX至发生全血细胞减少的时间为(7±3)d,范围3~19 d。WBC、Hb和PLT最低值分别为(0.80±0.55)×10^9/L、(70±22)g/L和(30±27)×10^9/L;10例患者有红细胞计数的描述,最低值为1.98×10^12/L;全血细胞减少严重程度2、3、4、5级者分别为5例(27.8%)、6例(33.3%)、1例(5.6%)和6例(33.3%)。主要临床表现为皮肤黏膜损害(18例)、发热(17例)、胃肠道反应(13例)。11例患者(61.1%)发生并发症,其中6例死亡。死亡患者WBC最低值的中位数明显低于存活患者[0.35(0.20~0.60)×10^9/L比0.83(0.22~1.80)×10^9/L,Z=2.722,P=0.007],而死亡和存活患者MTX总剂量、全血细胞减少发生时间、Hb和PLT最低值差异均无统计学意义(均P>0.05)。结论全血细胞减少为MTX治疗异位妊娠时罕见但致命的不良反应,WBC越低预后越差。

Objective To explore the clinical characteristics of pancytopenia induced by methotrexate(MTX)in treatment for patients with ectopic pregnancy.Methods The diagnosis and treatment of a case of pancytopenia induced by MTX in treatment for a patient with ectopic pregnancy in China⁃Japan Friendship Hospital were reported.The main clinical features of this case and the related cases collected from CNKI,Wanfang,VIP,and PubMed databases(as of June 30,2020)were summarized and analyzed.The total dose of MTX,time from the first dose of MTX to onset of pancytopenia,and lowest values of white blood cell count(WBC),hemoglobin(Hb),and platelet count(PLT)between the dead and the surviving patients were compared.Results A total of 18 patients were included in the analysis,aged from 20 to 41 years with an average age of 30 years.Among them,2 patients were suffering from chronic kidney disease and undergoing renal dialysis.The time from the first dose of MTX to onset of pancytopenia in patients was(7±3)days,ranging from 3 to 19 days.The lowest values of WBC,Hb,and PLT were(0.80±0.55)×10^9/L,(70±22)g/L,and(30±27)×10^9/L,respectively.Red blood cell count values were descripted in 10 patients and the lowest value was 1.98×10^12/L.The severity of pancytopenia were defined as grade 2,grade 3,grade 4,and grade 5 in 5 patients(27.8%),6 patients(33.3%),1 patient(5.6%),and 6 patients(33.3%),respectively.The main clinical manifestations were skin and mucous membrane damage(in 18 patients),fever(in 17 patients),and gastrointestinal reaction(in 13 patients).Eleven patients(61.1%)had complications and 6 of them died.The median value of the lowest WBC in the dead patients was significantly lower than that in the surviving patients[0.35(0.20-0.60)×10^9/L vs.0.83(0.22-1.80)×10^9/L,Z=2.722,P=0.007],whereas the differences in the total dose of MTX,time to onset of pancytopenia,or lowest values of Hb and PLT between the dead and the surviving patients were not statistically significant(all P>0.05).Conclusion Pancytopenia is a rare but fatal adverse reaction of MTX in treatment for patients with ectopic pregnancy and patients with lower WBC often have a worse prognosis.