A correlation study of the efficiency of warfarin and polymorphisms of vitamin K epoxide reductase complex subunit 1 gene after cardiac valve replacement

Abstract

Objective To investigate the clinical efficiency of oral warfarin after cardiac valve replacement and the influence of vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphisms on warfarin maintenance dose.Methods One hundred and fifty-nine patients who got cardiac valve replacement surgery were chosen and received anticoagulation therapy by oral warfarin.The prothrombin time (PT),international normalized ratio (INR) of patients were recorded and the safety ranges of PT and INR were calculated statistically.VKORC1 gene polymorphism of patients were detected by PCR-PFLP technology by adjusting the dose of warfarin,and the results were compared.Results The safety monitoring range of PT of oral warfarin after cardiac valve replacement surgery was 15.36 -24.82 s,safety monitoring range of INR was 1.33 - 2.62.The occurrence rate of bleeding during anticoagulation was 13.21％(21/159).The weekly dose of warfarin of VKORC1 gene type AA [(24.28 ± 10.79) mg] was significantly higher than that of VKORC1 gene type GA[ ( 16.64 ± 7.43 ) mg] and type GG[ ( 12.12 ± 7.17 ) mg](P＜ 0.05or ＜0.01 ).Conclusions The polymorphism of VKORC1 gene is the dominant factor of the differences of warfarin maintenance dose.The warfarin dose in patients with different gene type is different.The clinical safety monitoring ranges of PT and INR in patients with oral warfarin after cardiac valve replacement are lower than the recommended ranges of European and American countries.Therefore,the index of patients after surgery should be detected regularly. Key words: Warfarin; International normalized ratio; Heart valve replacement surgery