Impact of Factor VII Polymorphism on Responsiveness to Warfarin Anticoagulant Therapy

Abstract

Background: Oral anticoagulants (OAs) are drugs prescribed to reduce the risk of stroke and systemic embolism in non-valvular atrial fibrillation patients, and to treat and decrease the incidence of deep vein thrombosis and pulmonary embolism. We aimed to clarify the impact of factor VII (FVII) polymorphism on the extent of anticoagulation exerted by warfarin therapy. Methods: The study was performed on 30 patients on warfarin therapy with international normalized ratio (INR) 2-3, 21 of them for cardiac causes, 2 of them for orthopedic causes and the remaining 7 patients for vascular causes. They were subjected to warfarin therapy (Marevan), laboratory investigations (Prothrombin time (PT) and INR, FVII activity by coagulometric method, plasma warfarin level (by high performance liquid chromatography), and detecting FVII polymorphism (-401G/T & -402 G/A) by polymerase chain reaction). Results: Regarding the coagulation indicators of the patients with various FVII- 402 genotypes, PT time was significantly lower in homozygous mutant than heterozygous (P=0.032). Also, it was non significantly lower than that of wild type. PT time was non significantly lower in wild type than heterozygous. PT activity was significantly higher in homozygous mutant than heterozygous (P=0.032). Also, it was non significantly higher than that of wild type. PT activity was non significantly higher in wild type than heterozygous. There was significant difference as regard warfarin sensitivity index (WSI) between wild type and homozygous mutant. Marevan dose was significantly lower in wild type than homozygous mutant and heterozygous. Regarding the coagulation indicators of the patients with various FVII -401 genotypes, WSI was lower in wild type than heterozygous and homozygous mutant, however, it was significantly different between wild type compared to homozygous and heterozygous genotypes (P<0.001). Marevan dose was significantly higher in wild type than homozygous mutant (P<0.001), and it was non significantly higher in heterozygous than homozygous mutant. Conclusions: Marevan dose was significantly lower in wild type than homozygous and heterozygous mutant as regard FVII -402 G/A, while regarding FVII -401 G/T, marevan dose was significantly higher in wild type than homozygous mutant. Polymorphisms in FVII genes may play a significant role in modulating the warfarin’s anticoagulant effect.