Eljilany Islam, Elarref Mohamed, Shallik Nabil, Elzouki Abdel-Naser, Bader Loulia, El-Bardissy Ahmed, Abdelsamad Osama, Al-Badriyeh Daoud, Cavallari Larisa H, Elewa Hazem
College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
Department of Anesthesia, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.
Pharmgenomics Pers Med. 2021 Aug 28;14:1069-1080. doi: 10.2147/PGPM.S322743. eCollection 2021.
Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management.
An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in , and (rs5896) and (rs3093229) genes using real-time polymerase chain reaction were performed.
Data from 116 patients were included in the analysis. and genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, =0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure.
Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate.
每年，10%的华法林治疗患者可能需要在择期手术前停用华法林，以便在手术时达到国际标准化比值（INR）基线水平（INR≤1.2）。本研究探讨遗传和非遗传因素对中东地区阿拉伯人群术前华法林管理中INR正常化的影响。
设计一项观察性前瞻性队列研究，招募服用华法林并计划进行择期手术的阿拉伯患者。记录两次INR读数。采用实时聚合酶链反应对CYP2C9、VKORC1（rs5896）和CYP4F2（rs3093229）基因的变异进行DNA提取和基因分型。
116例患者的数据纳入分析。与非携带者相比，CYP2C9和VKORC1基因变异携带者所需的维持剂量更低。分析表明，环丙沙星、抗血小板药物和INR指数（首次就诊时的INR）是与INR下降率相关的唯一因素。此外，手术当天INR正常（≤1.2）的CYP2C9携带者比例显著低于野生型基因型携带者（28%对60%，P=0.013）。此外，肝素桥接、INR目标和苏丹国籍是手术当天INR正常化（≤1.2）的重要预测因素。
尽管遗传因素对华法林维持剂量的影响已得到证实，但由于样本量小，本研究未能发现任何遗传因素对INR正常化率有显著影响。首次就诊时的INR和相互作用的药物是INR下降率的重要预测因素。
