贝伐珠单抗联用卡瑞利珠单抗致严重消化道出血  

Severe gastrointestinal hemorrhage due to concomitant use of bevacizumab and camrelizumab

作　　者：尹岳松 石岩硕 吴玉佩 赫立恩[2] 徐晓飞 范晓燕[1] Yin Yuesong;Shi Yanshuo;Wu Yupei;He Lien;Xu Xiaofei;Fan Xiaoyan(Department of Oncology,Hebei General Hospital,Shijiazhuang 050051,China;Department of Pharmacy,Hebei General Hospital,Shijiazhuang 050051,China)

机构地区：[1]河北省人民医院肿瘤科,石家庄050051 [2]河北省人民医院药学部,石家庄050051

出　　处：《药物不良反应杂志》2024年第11期702-704,共3页Adverse Drug Reactions Journal

基　　金：河北省医学科学研究课题计划(20242006)。

摘　　要：1例67岁男性患者因肝内胆管癌接受奥沙利铂(肝动脉灌注)+吉西他滨(肝动脉灌注)+卡瑞利珠单抗(静脉滴注)+阿帕替尼(口服)治疗。2个月后(阿帕替尼已自行停用)发现血小板计数(PLT)下降(49×10^(9)/L),给予升血小板治疗后改善。因多发肿瘤转移,加用贝伐珠单抗(肝动脉灌注、1次/30 d)。用药前患者PLT和凝血功能均未见明显异常,用药2个周期后,患者PLT 101×10^(9)/L、凝血酶原时间14.1 s。考虑介入治疗出血风险大,停用奥沙利铂和吉西他滨,将贝伐珠单抗改为静脉滴注。PLT和凝血功能未见明显改善。第5次应用贝伐珠单抗6 d后,患者间断呕血2次(约300 ml)。实验室检查示PLT 75×10^(9)/L、凝血酶原时间15.8 s。诊断为消化道出血,予禁食禁水,行抑酸、止血、肠外营养支持等治疗,患者未再呕血,但间断排黑便。胃镜检查提示十二指肠溃疡伴出血,加用雷贝拉唑、硫糖铝等,停禁食、改流食。次日患者出现鲜血便,判断消化道出血与应用卡瑞利珠单抗和贝伐珠单抗有关,行动脉栓塞止血术,并给予A型冷沉淀凝血因子等治疗,出血症状稍好转。但患者病情反复,最终抢救无效死亡。A 67‑year‑old male patient with intrahepatic bile duct carcinoma was treated with oxaliplatin(hepatic artery perfusion)+gemcitabine(hepatic artery perfusion)+camrelizumab(intravenous infusion)+apatinib(oral).Platelet count(PLT)decline(49×10^(9)/L)was observed after 2 months(apatinib had been discontinued by himself),which was improved after platelet elevating therapy.Due to multiple tumor metastases,bevacizumab(hepatic arterial perfusion,once per 30 days)was added.Before bevacizumab treatment,PLT and coagulation function of the patient were basically no abnormalities.After 2 cycles of treatments,the PLT was 101×10^(9)/L and prothrombin time was 14.1 s.Considering the high risk of bleeding in interventional therapy,oxaliplatin and gemcitabine were discontinued,and bevacizumab administration was changed to intravenous infusion.PLT and coagulation function were not improved.Six days after the 5th dose of bevacizumab,the patient had intermittent hematemesis twice(about 300 ml).Laboratory tests showed PLT 75×10^(9)/L and prothrombin time 15.8 s.The patient was diagnosed with digestive tract hemorrhage.Fasting and water restriction was performed,and gastric acid suppression,hemostasis,parenteral nutrition,etc.were given.The patient had no hematemesis but intermittent black stool.Gastroscopy indicated duodenal ulcer accompanied by bleeding.Rabeprazole and sucralfate were added.Fasting was stopped and liquid diet was given.The next day,the patient had blood in the stool,and the bleeding of the lower digestive tract was judged to be related to camrelizumab and bevacizumab.The bleeding symptoms were slightly improved after treatments with arterial embolization hemostasis and type A cryopprecipitation coagulation factor,etc.Later,the patient had repeated bleeding condition,and finally died despite of rescue efforts.

关 键 词：胃肠出血 血小板减少 血管内皮生长因子类 免疫检查点抑制剂 贝伐珠单抗 卡瑞利珠单抗 

分 类 号：R969[医药卫生—药理学]