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.
Declaration of Institution Approval
This study was approved to publish the case details by our hospital.
Acknowledgments
Written informed consent to publish this case report was obtained from the patient and her family member. The reason why we let the patient and her family member sign the informed consent is the dose of warfarin was very high and exceeded many times more than the traditional dosage. That dosage would greatly increase the bleeding risk. In order to ensure the patient takes the drug and adheres to it, we obtained the consent of the patient and her family member who was in charge of taking care of the patient in hospital.
We thank our colleagues Xiaoxue Wang and Wangjun Qin at the Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China. We also thank Professor Zhenguo Zhai from the Department of Respiratory and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, China for their continuous help support.
Disclosure
The authors declare no conflict of interest.