One Rare Warfarin Resistance Case and Possible Mechanism Exploration.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2023-01-01 DOI:10.2147/PGPM.S404474
Li Zhao, Zhenguo Zhai, Pengmei Li
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Abstract

One 59-year-old female patient with deep venous thrombosis (DVT) and pulmonary embolism (PE) was treated with 6 mg warfarin once daily as an anticoagulant. Before taking warfarin, her international normalized ratio (INR) was 0.98. Two days after warfarin treatment, her INR did not change from baseline. Due to the high severity of the PE, the patient needed to reach her target range (INR goal = 2.5, range = 2~3) rapidly, so the dose of warfarin was increased from 6 mg daily to 27 mg daily. However, the patient's INR did not improve with the dose escalation, still maintaining an INR of 0.97-0.98. We drew a blood sample half an hour before administering 27 mg warfarin and detected single nucleotide polymorphism for the following genes, which were identified to be relevant with warfarin resistance: CYP2C9 rs1799853, rs1057910, VKORC1 rs9923231, rs61742245, rs7200749, rs55894764, CYP4F2 rs2108622, and GGCX rs2592551. The trough plasma concentration of warfarin was 196.2 ng/mL after 2 days of warfarin administration with 27 mg QD, which was much lower than the therapeutic drug concentration ranges of warfarin (500-3,000 ng/mL). The genotype results demonstrate that the CYP4F2gene has rs2108622 mutation which can explain some aspect of warfarin resistance. Further investigations are necessary to fully characterize other pharmacogenomics or pharmacodynamics determinants of warfarin dose-response in Chinese.

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一例罕见的华法林耐药病例及其可能的机制探讨。
1例59岁女性深静脉血栓(DVT)合并肺栓塞(PE)患者给予华法林6 mg抗凝治疗,每日1次。服用华法林前,其国际标准化比值(INR)为0.98。华法林治疗2天后,患者的INR与基线相比没有变化。由于PE的严重程度高,患者需要迅速达到目标范围(INR目标= 2.5,范围= 2~3),因此华法林的剂量从每天6mg增加到27mg。然而,患者的INR并没有随着剂量的增加而改善,仍然维持在0.97-0.98之间。在给药27 mg华法林前半小时采血,检测与华法林耐药相关基因CYP2C9 rs1799853、rs1057910、VKORC1 rs9923231、rs61742245、rs7200749、rs55894764、CYP4F2 rs2108622、GGCX rs2592551的单核苷酸多态性。以27 mg QD给药2 d后华法林血药谷浓度为196.2 ng/mL,远低于华法林治疗药物浓度范围(500 ~ 3000 ng/mL)。基因分型结果表明cyp4f2基因存在rs2108622突变,可以解释华法林耐药的某些方面。中国华法林剂量反应的其他药物基因组学或药效学决定因素需要进一步研究。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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