Warfarin Therapy

Warfarin (4-hydroxycumarin) (Coumadin; Bristol-Myers, Squibb) competitively inhibits vitamin K, an essential cofactor for the post-transitional carboxylation of glu-tamic acid residues on factors II, VII, IX, and X. Coumadin is the trade name for the most commonly available warfarin preparation.

A loading dose of 0.2 mg/kg by mouth as a single daily dose (maximum initial dose, 10 mg) should be employed when the International Normalized Ratio (INR) is less than 1.3. When it is greater than 1.3, reduce the loading dose to 0.1 mg/kg. For a patient with Fontan procedure or liver dysfunction, the daily dose should be reduced by 50%.

The subsequent dose is age dependent (infants having the highest—0.32 mg/kg— and teenagers the lowest—0.09 mg/kg) and based on the INR response (see the following table). Before the INR was adopted, the prothrombin time (PT) test was used for many years to control oral anticoagulant therapy. The variability of different thromboplastin reagents and instruments used in the performance of the PT made the transferability of results among laboratories difficult and impeded the development of universal guidelines for patient therapy.

Warfarin Daily Loading Doses (Approximately 3-5 Days)

INRa

Warfarin loading doses

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