NEWS(spring '05). - Douglass Hanly Moir Pathology

Warfarin ManagementWarfarin is one of the most commonly prescribed drugs.It is used as prophylaxis against thrombosis in the venousand arterial vasculature. It is effective in reducing the riskof thrombosis but has a narrow therapeutic window. Thereare only a few alternative drugs especially for long-termprophylaxis against thrombosis. Therefore the decision toanticoagulate a patient with warfarin is a decision to choosethe lesser of two evils.The therapeutic effect of warfarin is assessed with the INR(international normalised ratio for the prothrombin time). Theeffectiveness of warfarin has been shown in clinical trialsto be related to the INR, both the absolute level and thestability. Similarly, the side effects of warfarin therapy maybe related to high INR and variability of the INR.The rest of the article will concentrate on matters that mayinfluence the variability of the INR. The following are someof my thoughts about warfarin management that maybe helpful.Patient FactorsDoseDr Jonathan BlackwellHaematologistA forgotten a dose of warfarin is not infrequent. The patientshould not take extra, but be encouraged to be diligent withwarfarin doses. Testing too soon after the missed dosee.g. within three days, is likely to be misleading.I am sometimes asked why some patients require muchlarger doses of warfarin than others, i.e. seem to be“resistant” to warfarin. Genetic factors leading to differentmetabolism are increasingly recognised as a cause of widevariation in warfarin doses between patients. This type ofprofiling is still only used in clinical research.DietHigh dietary Vitamin K intake will reduce the INR. Greenleafy vegetables such as spinach, cabbage or cauliflowerare well known. Some cheeses, nuts and liver products areother foods high in vitamin K.Variation in the intake of Vitamin K rich foods from day today may lead to increased INR variability.Warfarin is well absorbed from the gut. Small bowel diseaseor poor oral intake will reduce the Vitamin K absorption andtherefore increase the INR.Malnutrition or intercurrent illness will affect warfarin proteinbinding and may increase the INR.AlcoholAlcohol consumption that is high and chronic may increasethe clearance of warfarin and therefore decrease the INR. Apatient with liver dysfunction will, however, have decreasedsynthesis of coagulation factors and therefore may haveincreased sensitivity to warfarin. Small regular amounts ofalcohol do not have a great influence on the INR.Understating alcohol consumption, particularly “bingeing”, isa common cause of variable INR.MedicationsMany drugs may potentiate warfarin and therefore increasethe INR.Some Drugs increasing the INRCotrimoxazoleErythromycinMetronidazoleIsoniazidAmiodaroneClofibrateOmeprazolePhenylbutazoneSome Drugs decreasing the INRCholestyramineRifampicinCarbamazepineSucralfateBarbiturates3