妊娠早期暴露低剂量华法林钠片后致胎儿畸形2例分析  

Two cases of fetal malformation after exposure to low dose warfarin sodium tablets in early pregnancy

作　　者：杨彩华[1] 杨龙娜 李小波 YANG Caihua;YANG Longna;LI Xiaobo(Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou Guangdong 510515,China;Nursing Department of Zhuhai Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine,Zhuhai Guangdong 519020,China;Department of Pharmacy,Zhuhai Hospital of Integrated Traditional Chinese Medicine and Western Medicine,Zhuhai Guangdong 519020,China)

机构地区：[1]南方医科大学南方医院临床药学中心,广东广州510515 [2]广东省中医院珠海医院护理部,广东珠海519020 [3]珠海中西医结合医院药学部,广东珠海519020

出　　处：《中国药物警戒》2023年第11期1286-1289,共4页Chinese Journal of Pharmacovigilance

基　　金：中国药学会科技开发中心项目[CMEI2022KPYJ(ZAMM)00601]。

摘　　要：目的 探讨母体妊娠早期暴露于低剂量华法林钠片后导致胎儿畸形的影响因素及药物遗传学效应。方法 报道2例心脏机械瓣膜置换术后妊娠女性服用低剂量(<5mg·d^(-1))华法林钠片抗凝治疗后出现胎儿唇腭裂和鼻骨发育短小的畸形病例,并综合文献分析胎儿畸形与低剂量华法林之间的药物相关性及其致畸分子机制。结果与结论 中国人群中,孕早期低剂量(<5 mg·d^(-1))华法林暴露存在胎儿口面部畸形风险,其致畸性与母体华法林剂量、暴露时间窗和个体间差异具有相关性。文献资料显示个体间CYP2C9、VKORC1基因多态性和ayl sulfatase E基因突变等也可能起关键作用,应引起临床重视。Objective To investigate the influencing factors and pharmacogenetic effects of fetal malformation caused by maternal exposure to low-dose warfarin sodium tablets during early pregnancy.Methods Two cases of fetal cleft lips and palates as well as short nasal bone development due to exposure to low-dose warfarin sodium tablets(< 5 mg·d^(-1)) during early pregnancy for anticoagulation after mechanical valve replacement were reported.The possible drug correlations and teratogenic molecular mechanism between fetal malformation and low-dose warfarin were discussed based on related literature.Results and Conclusion In Chinese populations,low-dose warfarin exposure(< 5 mg·d^(-1)) in early pregnancy can increase the risk of fetal oral-facial malformation,and its teratogenic mechanism may be correlated with the maternal warfarin dose,exposure time window and individual differences.Literature suggests that inter-individual CYP2C9,VKORC1 gene polymorphisms and AYL Sulfatase E gene mutations may also play a key role,which deserves clinical attention.

关 键 词：华法林钠片 妊娠 低剂量 唇腭裂 鼻骨发育不全 药品不良反应 

分 类 号：R972[医药卫生—药品] R994.11[医药卫生—药学]