[Genetic predisposition to bleeding during oral anticoagulants treatment].
The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagic risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion.
Montes Díaz
R
R
Laboratorio de trombosis y hemostasia, Universidad de Navarra, Pamplona, Spain. rmontes@unav.es
Nantes
O
O
Molina
E
E
Zozaya
J
J
Hermida
J
J
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D020022:Genetic Predisposition to Disease; D006470:Hemorrhage / Q000139:chemically induced* / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic; D014812:Vitamin K / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D014812:Vitamin K; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases