重组人粒细胞刺激因子注射液致冠状动脉血栓形成和血小板增多

Coronary thrombosis and thrombocytosis following subcutaneous injection of recombinant human granulocyte colony‑stimulating factor injection

1例23岁健康男性作为异体造血干细胞移植供体给予皮下注射重组人粒细胞刺激因子注射液(rhG‐CSF)600μg/d,共使用6 d。用药前患者的凝血标志物、血常规和血生化检查,以及心电图检查等均未见异常。停用该药7 d后患者突发胸痛、大汗、呕吐,实验室检查示高敏心肌肌钙蛋白T 3144 ng/L,肌酸激酶MB>300μg/L,肌红蛋白505.6μg/L,氨基末端脑利钠肽前体1138 ng/L,白细胞计数17.7×10^(9)/L,血小板计数(PLT)160×10^(9)/L。心电图检查示ST段抬高型心肌梗死。给予阿司匹林和替格瑞洛双联抗血小板治疗并行经皮冠状动脉腔内成形术,术后予抗凝、抗血小板、降脂等治疗。术后第3天患者出现脚趾疼痛、发热,PLT 382×10^(9)/L,经对症处理后症状逐渐缓解,但PLT 566×10^(9)/L。经血液科和风湿科医师会诊,结合相关实验室检查指标,排除自身免疫和血液系统相关疾病,考虑冠状动脉血栓形成和血小板增多可能与使用rhG‐CSF相关,未予特殊处理,PLT逐渐下降至275×10^(9)/L。7个月后随访患者PLT 235×10^(9)/L。

A 23‐year‐old healthy male received subcutaneous injection of recombinant human granulocyte colony‐stimulating factor injection(rhG-GSF)600μg once daily for 6 days before allogeneic hematopoietic stem cell transplantation as a donor.Before medication,there were no abnormalities in the patient′s coagulation markers,blood routine and biochemical tests,as well as electrocardiographic examination.Seven days after discontinuation of the drug,the patient developed sudden chest pain,sweating,and vomiting.Laboratory tests showed high sensitivity cardiac troponin T 3144 ng/L,creatine kinase MB>300μG/L,myoglobin 505.6μg/L,N‐terminal pro-brain natriuretic peptido 1138 ng/L,white blood cell count 17.7×10^(9)/L,platelet count 160×10^(9)/L.The electrocardiogram showed ST segment elevation myocardial infarction.A dual antiplatelet therapy of aspirin and ticagrelor was administered in conjunction with percutaneous transluminal coronary angioplasty.After surgery,anticoagulation,antiplatelet,and lipid‐lowering treatments were given.On the 3rd day after surgery,the patient developed toe pain,fever,and a platelet count of 382×10^(9)/L,symptoms were gradually relieved after symptomatic treatment,but platelet count increased to 566×10^(9)/L.After consultation with hematologists and rheumatologists,combined with relevant laboratory test indicators,autoimmune and hematological system-related diseases were excluded.It was considered that coronary artery thrombosis and thrombocytosis may be related to the use of rhG‐CSF,and platelet count gradually decreased to 275×10^(9)/L without special treatment.During the follow‐up of 7 months,his platelet count was 235×10^(9)/L.