Five VEGFA Polymorphisms and Bleeding During Warfarin Therapy in a Saudi Population: An Exploratory Retrospective Cohort Study.

BACKGROUND: Warfarin remains a widely used anticoagulant for long-term thromboprophylaxis, but its narrow therapeutic index and substantial interindividual variability increase the risk of bleeding complications. Functional variants in vascular endothelial growth factor A (VEGFA) may therefore influence vascular integrity during anticoagulant therapy. This study investigated the association between functional VEGFA polymorphisms and warfarin-associated bleeding in a Saudi cohort. METHODS: In this retrospective cohort study, 161 Saudi patients receiving stable maintenance warfarin therapy were genotyped for five VEGFA single-nucleotide polymorphisms (SNPs): rs699947, rs833069, rs2010963, rs35410204, and rs866236. Clinical characteristics and bleeding events during warfarin therapy were obtained from electronic medical records. Bleeding status was determined from clinically documented bleeding events during warfarin therapy that required medical evaluation, hospitalization, or blood transfusion. Genotype-phenotype associations were assessed using chi-square analysis and a multivariable logistic regression model. RESULTS: Bleeding occurred in 39% of the patients (63/161). Among the five VEGFA variants studied, rs699947 and rs833069 showed associations with bleeding in bivariate analysis. The rs699947 A/A genotype and rs833069 T/T genotype were less frequent in patients with bleeding than in those without bleeding (6.7% vs 25.5%, p = 0.009; and 16.4% vs 37.5%, p = 0.013, respectively). The rs833069 association did not survive Bonferroni correction for multiple testing and is therefore considered exploratory. Following adjustment for age, sex, body mass index, international normalized ratio, systolic blood pressure, and diastolic blood pressure, rs699947 remained significantly associated with bleeding. For rs833069, the overall genotype association remained statistically significant; however, individual genotype comparisons were not statistically significant. For rs699947, the A/A genotype was associated with lower odds of bleeding compared with the C/C genotype (OR 0.249, 95% CI 0.062-0.999; p = 0.050). No significant associations were observed for rs2010963, rs35410204, or rs866236. CONCLUSION: In this exploratory retrospective cohort study, VEGFA rs699947 and rs833069 showed possible associations with bleeding during warfarin therapy in Saudi patients. These findings provide preliminary evidence that VEGFA polymorphisms may contribute to bleeding susceptibility during warfarin therapy. Given the modest sample size, these findings should be interpreted cautiously and require validation in larger prospective studies.