Anticoagulation Clinic currently cares for more than

walk a tightrope between bleeding and clot-ting—and a hundred things can tip the balance. It’s a difficult drug to use, with a narrow therapeu-tic index, but 60 years after it was introduced it is still the mainstay of oral anticoagulant treatment. More than 2 million North Americans take it, and this number continues to grow with our aging pop-ulation.1 Only a minority of these patients are man-aged by anticoagulation clinics, despite evi-dence that patients managed by anticoagula-tion clinics have fewer bleeding and throm-boembolic events than those who receive usual medical care,2,3 and their international normalized ratios (INRs) are in the therapeu-tic range a greater percentage of the time.4–7 Therefore, everyone who prescribes war-farin, whether a cardiologist, family physician, or internist, needs to understand: • Warfarin’s mechanism of action • Its pharmacokinetics and pharmacody-namics • Its multiple interactions with other drugs, diet, and disease states • How to use the INR to determine the dose of warfarin and monitor its anticoagulant effect. In the pages that follow we offer some practical tips on the art and science of using warfarin safely and effectively. n MECHANISM OF ACTION Warfarin, a coumarin derivative, inhibits clot-ting by limiting hepatic production of the bio-logically active vitamin K-dependent clotting factors (activated factors II, VII, IX, and X). Normally, the precursors of these factor