Thromb Haemost 2000; 84(05): 775-778
DOI: 10.1055/s-0037-1614114
Review Article
Schattauer GmbH

Genetic Modulation of Oral Anticoagulation with Warfarin

Maurizio Margaglione
1   From Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy
,
Donatella Colaizzo
1   From Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy
,
Giovanna D’Andrea
1   From Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy
,
Vincenzo Brancaccio
2   Divisione di Ematologia, Unità di Coagulazione, Ospedale “A. Cardarelli”, Napoli, Italy
,
Antonio Ciampa
3   Divisione di Ematologia, Ospedale “G. Moscati”, Avellino, Italy
,
Elvira Grandone
1   From Unita’ di Aterosclerosi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Italy
,
Giovanni Di Minno
4   Istituto di Medicina Interna e Geriatria, Università di Palermo, Italy
› Author Affiliations
Further Information

Publication History

Received 22 December 1999

Accepted after resubmission 19 June 2000

Publication Date:
13 December 2017 (online)

Summary

Cytochrome P450 CYP2C9 gene variants have been associated with hyperresponsiveness to small doses of warfarin and a higher bleeding complication rate. The aim of this study was to investigate whether CYP2C9 gene variants affect doses of drug prescribed to acquire the target anticoagulation intensity and the occurence of bleeding complications. In a cohort of 180 patients followed up at one specialized clinic from the start of the anticoagulation with warfarin, we have investigated whether CYP2C9 gene variants have affected doses of drug prescribed to acquire the target anticoagulation intensity and the incidence of bleeding complications.

The adjusted dose required of warfarin was higher among patients with the CYP2C9*1 haplotype (5.6 mg) than those of patients carrying the CYP2C9*2 (4.7 mg; p = 0.007, Scheffé’s test) or the CYP2C9*3 haplotype (4.0 mg; p <0.001, Scheffé’s test). The occurrence of bleeding complications was more frequent among patients with the CYP2C9*2 and/or the CYP2C9*3 haplotype than in carriers of the CYP2C9*1 haplotype (OR: 2.57; 95% CI: 1.16–5.73). An interaction between the presence of local bleeding sources and the CYP2C9*2 and/or the CYP2C9*3 haplotype was observed (p <0.001). Patients with both local sites of potential bleeding and CYP2C9*2 and/or the 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 dose of warfarin prescribed. The incidence of bleeding complications in CYP2C9*2 and CYP2C9*3 carriers was significantly higher than that in noncarriers and interacted with the presence of local bleeding sources.

 
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