Botton Mariana R, Viola Patrícia P, Meireles Mariana R, Bruxel Estela M, Zuchinali Priccila, Bandinelli Eliane, Rohde Luis E, Leiria Tiago L L, Salamoni Joyce Y Y, Garbin Arthur P, Hutz Mara H
Universidade Federal do Rio Grande do Sul, Departamento de Genética, Porto Alegre, RS, Brazil.
Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
Genet Mol Biol. 2020 Feb 10;43(1 suppl 2):e20190025. doi: 10.1590/1678-4685-GMB-2019-0025. eCollection 2020.
Warfarin is an oral anticoagulant prescribed to prevent and treat thromboembolic disorders. It has a narrow therapeutic window and must have its effect controlled. Prothrombin test, expressed in INR value, is used for dose management. Time in therapeutic range (TTR) is an important outcome of quality control of anticoagulation therapy and is influenced by several factors. The aim of this study was to identify genetic, demographic, and clinical factors that can potentially influence TTR. In total,422 patients using warfarin were investigated. Glibenclamide co-medication and presence of CYP2C9*2 and/or 3 alleles were associated with higher TTR, while amiodarone, acetaminophen and verapamil co-medication were associated with lower TTR. Our data suggest that TTR is influenced by co-medication and genetic factors. Thus, individuals in use of glibenclamide may need a more careful monitoring and genetic testing (CYP2C92 and/or *3 alleles) may improve the anticoagulation management. In addition, in order to reach and maintain the INR in the target for a longer period, it is better to discuss dose adjustment in office instead of by telephone assessment. Other studies are needed to confirm these results and to find more variables that could contribute to this important parameter.
华法林是一种口服抗凝剂，用于预防和治疗血栓栓塞性疾病。它的治疗窗较窄，必须控制其效果。用国际标准化比值（INR）表示的凝血酶原试验用于剂量管理。治疗范围内时间（TTR）是抗凝治疗质量控制的一项重要指标，受多种因素影响。本研究的目的是确定可能影响TTR的遗传、人口统计学和临床因素。总共对422名使用华法林的患者进行了调查。格列本脲联合用药以及CYP2C92和/或3等位基因的存在与较高的TTR相关，而胺碘酮、对乙酰氨基酚和维拉帕米联合用药与较低的TTR相关。我们的数据表明，TTR受联合用药和遗传因素影响。因此，使用格列本脲的个体可能需要更密切的监测，基因检测（CYP2C92和/或3等位基因）可能会改善抗凝管理。此外，为了在更长时间内使INR达到并维持在目标范围内，最好在门诊讨论剂量调整，而不是通过电话评估。需要其他研究来证实这些结果，并找到更多可能影响这一重要参数的变量。
