Arakaki Shintaro, Ono Shinichiro, Kawamata Futoshi, Ishino Shinichiro, Uesato Yasunori, Nakajima Tomo, Nishi Yukiko, Morishima Satoko, Arakaki Shingo, Maeshiro Tatsuji, Souri Masayoshi, Ichinose Akitada, Masuzaki Hiroaki, Takatsuki Mitsuhisa
Department of Digestive and General Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Surg Case Rep. 2023 Feb 2;9(1):16. doi: 10.1186/s40792-023-01601-2.
Atezolizumab plus bevacizumab therapy was recently introduced as the first line for unresectable advanced hepatocellular carcinoma (HCC), but immune-related adverse events (IrAEs) due to atezolizumab are a great concern. Here, we report the case of a patient who developed fatal acquired coagulation factor deficiency after hepatectomy for HCC, treated with atezolizumab and bevacizumab before surgery.
A 70-year-old man received right trisegmentectomy of the liver with hepaticojejunostomy for advanced HCC with bile duct invasion, after atezolizumab and bevacizumab therapy. The patient suffered the sudden onset of severe multiple coagulation factor deficiency (II, V, VII, VIII, IX, X, XI and XII) immediately following reoperation for anastomotic leakage of hepaticojejunostomy, 7 days after hepatectomy. The coagulation factor deficiency did not reverse even with intensive treatment, and the patient died of uncontrollable bleeding 32 days after hepatectomy. An IrAE due to atezolizumab was suspected because the patient had developed the possible IrAE of enthesitis of the right gastrocnemius muscle before surgery, and specific inhibitors against factor V and anti-factor V autoantibodies were detected, leading to an ultimate diagnosis of autoimmune FV/5 deficiency (AiF5D).
Severe acquired coagulopathy should be recognized as a possible life-threatening IrAE when using atezolizumab and bevacizumab for HCC.
阿替利珠单抗联合贝伐珠单抗治疗最近被引入作为不可切除的晚期肝细胞癌（HCC）的一线治疗方案，但阿替利珠单抗引起的免疫相关不良事件（IrAE）备受关注。在此，我们报告一例HCC肝切除术后发生致命性获得性凝血因子缺乏的患者病例，该患者在手术前接受了阿替利珠单抗和贝伐珠单抗治疗。
一名70岁男性在接受阿替利珠单抗和贝伐珠单抗治疗后，因晚期HCC伴胆管侵犯接受了右半肝切除及肝空肠吻合术。肝切除术后7天，患者在因肝空肠吻合口漏再次手术时，突然出现严重的多种凝血因子缺乏（II、V、VII、VIII、IX、X、XI和XII）。即使经过强化治疗，凝血因子缺乏仍未得到纠正，患者在肝切除术后32天死于无法控制的出血。由于患者在手术前出现了右腓肠肌肌腱附着点炎这一可能的IrAE，并检测到针对因子V的特异性抑制剂和抗因子V自身抗体，怀疑是阿替利珠单抗引起的IrAE，最终诊断为自身免疫性FV/5缺乏症（AiF5D）。
在使用阿替利珠单抗和贝伐珠单抗治疗HCC时，严重获得性凝血病应被视为一种可能危及生命的IrAE。
