■本研究旨在探讨直接口服抗凝药(DOACs)患者纤维蛋白原基因多态性与出血风险之间的关系。
■2018年6月至2021年12月接受DOAC治疗的患者纳入研究。对纤维蛋白原α链(FGA)中的rs2070011,rs6050和rs2070022进行基因分型;纤维蛋白原β链(FGB)中的rs1800788,rs4220和rs4463047;纤维蛋白原γ链(FGG)中的rs2066865和rs1800792,以及F2rs5896和F10rs5960。进行多变量logistic回归分析以调查出血的危险因素并开发风险评分系统。
■共468例患者纳入分析,其中14人经历了大出血,36人经历了临床相关的非大出血。在多变量分析中,用药过量,贫血,F2rs5896和FGGrs1800792与出血风险显著相关。具体来说,TT基因型F2rs5896和CC基因型FGGrs1800792患者的出血风险比C等位基因和T等位基因携带者高2.1倍(95%置信区间[CI]1.1-3.9)和2.7倍(95%CI1.2-5.9),分别。基于风险评分系统,预测0、1、2、3、4和5分的患者有5.2%,10.8%,22.4%,32.3%,42.3%,61.8%的出血风险,分别。
■据我们所知,这是首次研究纤维蛋白原基因多态性对DOAC反应的影响.验证后,这些结果将有助于个性化DOAC治疗.
UNASSIGNED: This study aimed to investigate the association between polymorphisms in fibrinogen genes and bleeding risk in patients receiving direct oral anticoagulants (DOACs).
UNASSIGNED: Patients treated with DOACs from June 2018 to December 2021 were enrolled in the study. Genotyping was done for rs2070011, rs6050, and rs2070022 in fibrinogen alpha chain (FGA); rs1800788, rs4220, and rs4463047 in fibrinogen beta chain (FGB); and rs2066865 and rs1800792 in fibrinogen gamma chain (FGG), along with F2 rs5896 and F10 rs5960. Multivariable logistic regression analysis was performed to investigate the risk factors for bleeding and to develop a risk scoring system.
UNASSIGNED: A total of 468 patients were included in the analysis, 14 of whom experienced major bleeding and 36 experienced clinically relevant non-major bleeding. In the multivariable analysis, overdose, anaemia, F2 rs5896, and FGG rs1800792 were found to be significantly associated with bleeding risk. Specifically, patients with the TT genotype of F2 rs5896 and the CC genotype of FGG rs1800792 had 2.1 times (95% confidence interval [CI] 1.1-3.9) and 2.7 times (95% CI 1.2-5.9) higher bleeding risk than the C allele and T allele carriers, respectively. Based on the risk scoring system, patients with 0, 1, 2, 3, 4, and 5 points were predicted to have 5.2%, 10.8%, 22.4%, 32.3%, 42.3%, and 61.8% of bleeding risk, respectively.
UNASSIGNED: To our knowledge, this is the first study to investigate the effects of polymorphisms in fibrinogen genes on DOAC response. After validation, these results will be useful for personalised DOAC therapy.