Optimal intensity and monitoring warfarin
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The risk of bleeding with warfarin can be markedly reduced without affecting efficacy by using a low-intensity therapeutic range. The reliability of warfarin monitoring has also improved with the development of the international normalized ratio (INR) to standardize prothrombin time despite use of nonuniform thromboplastins by different laboratories. There are 2 recommended therapeutic ranges of intensity for warfarin: the less intense corresponds to INR 2.0-3.0, the more intense, to INR 2.5-3.5. Dosage response to warfarin is influenced by concomitant medication, dietary vitamin K, hepatic dysfunction, and hypermetabolic states. For rapid anticoagulant effect, the initial dosage is 10 mg/day (plus heparin). For nonemergent treatment, the initial dosage is 4-5 mg/day, which achieves a steady-state anticoagulant effect in 5-7 days; this is also the anticipated maintenance dosage. Prothrombin time (PT) monitoring is performed daily until the therapeutic range is achieved, then progressively less often, depending on stability of PT results. Bleeding while on warfarin (INR > 3.0) may respond to reduced dosage; for severe bleeding, vitamin K reverses warfarin effects in 6-12 hours. Bleeding on low-intensity warfarin (INR < 3.0) suggests an underlying pathologic condition. Warfarin is contraindicated in pregnancy because of its teratogenicity but may be used by nursing mothers, as it does not pass into breast milk.