Key result
The CC genotype of FGG rs1800792 was associated with a 2.7 times higher bleeding risk compared to T allele carriers in patients treated with direct oral anticoagulants.
Why the study?
The association between genetic polymorphisms in fibrinogen genes and bleeding risk in patients receiving DOACs had not been investigated.
Do genetic polymorphisms in fibrinogen genes (F2 rs5896 and FGG rs1800792) increase bleeding risk in patients treated with direct oral anticoagulants?
Observational (n=468)
Yes
Do genetic polymorphisms in fibrinogen genes (F2 rs5896 and FGG rs1800792) increase bleeding risk in patients treated with direct oral anticoagulants?
Odds Ratio: 2.7 (95% CI 1.2–5.9)
p-value: p=<0.05
Genetic polymorphisms in fibrinogen genes (F2 rs5896 and FGG rs1800792), along with DOAC overdose and anaemia, are significant predictors of bleeding risk in Asian patients taking DOACs, enabling a novel personalized risk scoring system.
Fibrinogen gene variants may associate with DOAC bleeding risk; hypothesis-generating and leaves open clinical utility pending validation.
Introduction: This study aimed to investigate the association between polymorphisms in fibrinogen genes and bleeding risk in patients receiving direct oral anticoagulants (DOACs). Method: 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. Results: 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. Conclusion: 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.
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Choi et al. (2023) conducted an observational in Patients treated with direct oral anticoagulants (n=468). FGG rs1800792 CC genotype vs. T allele carriers was evaluated on Any 1-year bleeding event (major bleeding and clinically relevant non-major bleeding) (OR 2.7, 95% CI 1.2-5.9, p=<0.05). The CC genotype of FGG rs1800792 was associated with a 2.7 times higher bleeding risk compared to T allele carriers in patients treated with direct oral anticoagulants.
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