Genetic Modulation of Oral Anticoagulation with Warfarin
Maurizio Margaglione (1) , Donatella Colaizzo (1) , Giovanna D’Andrea (1) , Vincenzo Brancaccio (2) , Antonio Ciampa (3) , Elvira Grandone (1) , Giovanni Di Minno (4)
From (1) Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S. "Casa Sollievo della Sofferenza", S. Giovanni Rotondo, (2) Divisione di Ematologia, Unità di Coagulazione, Ospedale "A. Cardarelli", Napoli, (3) Divisione di Ematologia, Ospedale "G. Moscati", Avel
Summary Cytochrome P450 CYP2C9 gene variants have been associated withhyperresponsiveness to small doses of warfarin and a higher bleedingcomplication rate. The aim of this study was to investigate whetherCYP2C9 gene variants affect doses of drug prescribed to acquire thetarget anticoagulation intensity and the occurence of bleeding complications.In a cohort of 180 patients followed up at one specialized clinicfrom the start of the anticoagulation with warfarin, we have investigatedwhether CYP2C9 gene variants have affected doses of drug prescribedto acquire the target anticoagulation intensity and the incidenceof bleeding complications.The adjusted dose required of warfarin was higher among patientswith the CYP2C9*1 haplotype (5.6 mg) than those of patients carryingthe CYP2C9*2 (4.7 mg; p = 0.007, Scheffé’s test) or the CYP2C9*3haplotype (4.0 mg; p <0.001, Scheffé’s test). The occurrence of bleedingcomplications was more frequent among patients with theCYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of theCYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16-5.73). An interactionbetween the presence of local bleeding sources and the CYP2C9*2and/or the CYP2C9*3 haplotype was observed (p <0.001). Patientswith both local sites of potential bleeding and CYP2C9*2 and/orthe CYP2C9*3 haplotype had the higher estimated risk of bleeding(OR: 12.81; 95% CI: 2.86-57.26).CYP2C9 gene variants modulate the anticoagulant effect of the doseof warfarin prescribed. The incidence of bleeding complications inCYP2C9*2 and CYP2C9*3 carriers was significantly higher than thatin noncarriers and interacted with the presence of local bleedingsources.