![]() Anticoagulant services based in hospitals and the community involve doctors, nurses, pharmacists, and laboratory staff. These difficulties have led to the need for an entire warfarin associated industry and infrastructure devoted to the clinical use and therapeutic monitoring of this single drug. 9 Thus, interindividual variation in warfarin dosage requirements is the result of a complex interaction between environmental and genetic factors. 8 However, it may be clinically useful to screen those individuals who exhibit warfarin sensitivity because there is some suggestion that alternative vitamin K antagonists, such as acenocoumarol, may be safer in those individuals with particular variants. 6, 7 The prevalence of such genetic factors is not sufficiently high to warrant screening before the initiation of anticoagulation. 4, 5 In addition, a rare point mutation in the factor IX propeptide, leading to extremely low factor IX values during warfarin treatment and associated bleeding, has been described. 2, 3 Warfarin sensitivity and serious bleeding in individuals with variant alleles have been reported. Apparent differences in sensitivity to warfarin between ethnic groups have been described, 1 and mutations in the cytochrome P450 2C9 gene that lead to decreased enzyme activity and subsequent reduced warfarin metabolism have been well characterised. More recently, it has become clear that genetic factors that lead to differences in warfarin sensitivity are also important. There are many factors that have been reported to influence warfarin dose, including concomitant medication, diet, increasing age, liver volume, vitamin K status, and occult malignancy. Warfarin treatment is problematic because of the wide interindividual and intra-individual variation in dosage requirements. “Interindividual variation in warfarin dosage requirements is the result of a complex interaction between environmental and genetic factors” Multiple indications for longterm anticoagulation have become accepted, including patients with recurrent venous thrombosis, prosthetic heart valves, stroke prevention in atrial fibrillation, and anti-phospholipid syndrome. The anticoagulant effect of warfarin results from the inhibition of the γ carboxylation step in the synthesis of the vitamin K dependent clotting factors II, VII, IX, and X. There has been a dramatic increase in the number of patients receiving longterm anticoagulation with warfarin in recent years.
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