心脏机械瓣膜置换术后患者华法林维持剂量的影响因素分析

Influencing factors on warfarin maintenance dosage in patients after mechanical heart valve replacement

目的探讨心脏机械瓣膜置换术后患者华法林维持剂量的影响因素。方法选取2018年10月至2020年3月于新疆医科大学第一附属医院心脏外科行心脏机械瓣膜置换术后服用华法林抗凝,连续2次国际标准化比值(INR)达标的64例汉族和76例维吾尔族患者。记录所有患者临床资料,采用聚合酶链反应直接测序技术对维生素K环氧化物还原酶复合体亚单位1(VKORC1)基因位点进行基因分型。分析VKORC1基因多态性及性别、年龄、民族、体质量、身高、是否吸烟、是否患有高血压、糖尿病等因素对患者华法林维持剂量的影响。结果VKORC1基因rs9923231 A/G基因型和rs9934438 T/C基因型在汉族和维吾尔族患者中的分布差异有统计学意义(均P<0.05)。男性患者华法林维持剂量高于女性患者[(2.7±0.6)mg/d比(2.4±0.7)mg/d](P=0.021)。患者年龄越大,华法林维持剂量越小,而华法林维持剂量随着体质量的增加而增加(均P<0.05)。不同民族、不同身高、是否吸烟、是否高血压、是否糖尿病患者华法林维持剂量比较差异均无统计学意义(均P>0.05)。VKORC1基因rs9923231 A/G位点AA型患者华法林维持剂量低于AG型患者,rs9934438 T/C位点TT型患者华法林维持剂量低于TC型患者(均P<0.05)。结论VKORC1基因rs9923231 A/G、rs9934438 T/C位点和性别、年龄、体质量均可能影响心脏机械瓣膜置换术后患者华法林的维持剂量,临床用药时应尽可能全面考虑相关因素,为患者制定个体化治疗方案。

Objective To investigate the influencing factors of warfarin maintenance dosage in patients after mechanical heart valve replacement.Methods From October 2018 to March 2020,64 Han and 76 Uighur patients who took warfarin anticoagulant after cardiac mechanical valve replacement in Department of Cardiac Surgery,the First Affiliated Hospital of Xinjiang Medical University were selected.the international normalized ratio(INR)of all patients met the standard for two consecutive times.The clinical data of patients were recorded.Genotyping of vitamin K epoxide reductase complex 1(VKORC1)gene locus was performed by polymerase chain reaction direct sequencing.The effects of VKORC1 gene polymorphism,gender,age,nationality,body mass,height,smoking,hypertension and diabetes mellitus on the warfarin maintenance dosage were analyzed.Results There was significant difference in the distribution of VKORC1 gene rs9923231 A/G genotype and rs9934438 T/C genotype between Han and Uighur patients(all P<0.05).The warfarin maintenance dosage in male patients was higher than that in female patients[(2.7±0.6)mg/d vs(2.4±0.7)mg/d](P=0.021).The older the patients were,the smaller the warfarin maintenance dosagewas,and the warfarin maintenance dose increased gradually with the increase of body mass(all P<0.05).There were no significant differences in the warfarin maintenance dosage between different nationalities,different height,smoking,hypertension and diabetes mellitus(all P>0.05).The warfarin maintenance dose in patients with AA genotype at rs9923231 A/G locus of VKORC1 gene was lower than that in patients with AG genotype,and the warfarin maintenance dose in patients with TT genotype at rs9934438 T/C locus was lower than that in patients with TC genotype(all P<0.05).Conclusions VKORC1 rs9923231 A/G locus,rs9934438 T/C locus,gender,age and body mass are positively affecting the warfarin maintenance dose in patients after mechanical heart valve replacement,and these factors should be considered as comprehensively as possible to develop individualized treatment plan for clinical practice.