大剂量利巴韦林注射液致新型冠状病毒肺炎患者急性溶血反应2例

Acute hemolytic reaction in patients with novel coronavirus pneumonia induced by high-dose ribavirin injection:report of 2 cases

2例女性患者(例1,22岁;例2,50岁)均因新型冠状病毒肺炎给予利巴韦林注射液静脉滴注(首剂4 g,次日1.2 g、3次/d),洛匹那韦/利托那韦片口服,注射用重组人干扰素α2b雾化吸入。用药前患者血常规和肝功能未见明显异常。例1用药第2天红细胞计数(RBC)2.9×10^12/L,血红蛋白(Hb)75-g/L,丙氨酸转氨酶(ALT)22.8-U/L,天冬氨酸转氨酶(AST)33.9-U/L,总胆红素(TBil)71.2-μmol/L,间接胆红素(IBil)63.5-μmol/L。例2用药第3天RBC 3.5×10^12/L,Hb 95-g/L,ALT 17.7-U/L,AST 21.3-U/L,TBil 86.1-μmol/L,IBil 67.1-μmol/L。2例患者均直接抗人球蛋白试验阳性,间接抗人球蛋白试验阴性,抗核抗体谱检测阴性。诊断为急性溶血性贫血,考虑与利巴韦林注射液相关。例1利巴韦林减量至停用,例2直接停用利巴韦林,并均加用熊去氧胆酸,其余药物继续使用。2例患者血红蛋白和胆红素逐渐恢复正常。

Two female patients(patient 1,22-year-old;patient 2,50-year-old)received IV infusion of ribavirin injection(4 g in the first dose and the next day 1.2 g thrice daily),oral 2 lopinavir and ritonavir tablets twice daily,and aerosol inhalation of recombinant human interferonα2b for injection for novel coronavirus pneumonia.There was no obvious abnormality in blood routine and liver function before treatment.Laboratory tests showed red blood cell count(RBC)2.89×10^12/L,hemoglobin(Hb)75-g/L,alanine aminotransferase(ALT)22.8-U/L,aspartate aminotransferase(AST)33.9-U/L,total bilirubin(TBil)71.2-μmol/L,and indirect bilirubin(IBil)63.5-μmol/L in patient 1 on the 2nd day of treatment,and RBC 3.46×10^12/L,Hb 95-g/L,ALT 17.7-U/L,AST 21.3-U/L,TBil 86.1-μmol/L,and IBil 67.1-μmol/L in patient 2 on the 3rd day of treatment.The direct antiglobulin test was positive,indirect antiglobulin test was negative,and antinuclear antibody test was negative in both patients.They were diagnosed as having acute hemolytic anemia.Con-sidering the relationship to ribavirin,ribavirin was given in reduced dose and then finally discontinued in patient 1,and was discontinued directly in patient 2.On the basis of continued use of the other 2 drugs,both of them were treated with ursodeoxycholic acid.The Hb and bilirubin level of the 2 patients gradually returned to normal.