Optimising the dose of oral anticoagulants

Abstract

Oral anticoagulants, although valuable, can be dangerous if their use is not carefully monitored. Variability in response to warfarin due to a variety of factors means that initial dose is difficult to predict. The fixed dose regime for initiation of anticoagulant therapy (10 mg daily for three days) results in excessive anticoagulation in one third of patients. A flexible loading dose regime on the other hand, allows smooth initiation and it can also be used to predict maintenance dose. Warfarin therapy can be commenced along with heparin and it is probably unnecessary to continue the latter for more than five days in patients who are adequately anticoagulated with the former. Rational prediction of warfarin maintenance dose is difficult because of a variety of pharmacokinetic and pharmacodynamic factors. Several methods have been described and of these, a feed-back method that uses Bayesian technique is considered to be the most accurate. There is no evidence that computer-assisted methods of dosage prediction are better than empirical or semi-empirical methods. However, for most situations, clinical conditions requiring anticoagulant therapy, maintenance of an International Normalised Ratio (INR) of 2-3 is sufficient but for recurrent deep vein thromboses, recurrent pulmonary emboli, mechanical prosthetic valves and arterial disease including myocardial infarction an INR of 3-4.5 is recommended. Estimation of plasma warfarin and plasma warfarin clearance are valuable in determining the cause of abnormal responsiveness. Low doses of vitamin K, can be used to reverse over-anticoagulation without the risk of producing under-anticoagulation in patients who require long term treatment. Fresh frozen plasma or prothrombin complex may be necessary in patients who are bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)