The optimal warfarin dose for patients beginning therapy

Warfarin is used as an oral anticoagulant. However, there is wide variation in patient response to warfarin dose. This variation, as well as the necessity of keeping within a narrow therapeutic range, means that selection of the correct warfarin dose at the outset of treatment is not straightforward.

Warfarin is commonly prescribed to prevent blood clots in patients with medical conditions such as atrial fibrillation, heart valve replacement or previous blood clots. Warfarin is an effective treatment which has been used for many years but needs to be closely monitored, especially at the beginning of treatment, as there is a wide variation in response to dose. Monitoring of the response to dose is done using an International Normalized Ratio (INR) and it is important that patients remain within a narrow range (typically 2 to 3 INR) due to the need to balance the goal of preventing blood clots with the risk of causing excessive bleeding.

The use of warfarin is challenging not only due to its narrow therapeutic range but also because the dosing is affected by many factors including drug interactions and diet. Time spent with international normalized ratio (INR) above the therapeutic range increases the risk of bleeding, and time spent below the therapeutic range increases the risk of thromboembolic complications, which these agents were administered to prevent. Nevertheless, these agents have a large body of clinical experience and are highly effective in reducing the risk of venous and arterial thromboemboli in many settings.

The studies in this review compared loading doses in several different situations. There is still considerable uncertainty between the use of a 5 mg and a 10 mg loading dose for the initiation of warfarin. Some studies showed no difference between a 5 mg and 10 mg dose by day five. Two studies compared a 5 mg dose to other doses: a 2,5 mg initiation dose took longer to achieve the therapeutic range. In the elderly, there is some evidence that lower initiation doses or age adjusted doses are more appropriate, leading to fewer high INRs. 

Patients also require close monitoring for signs and symptoms of active bleeding throughout their treatment. Close monitoring for signs and symptoms of bleeding, such as dark tarry stools, nosebleeds, and hematomas, is necessary. The patient’s hemoglobin and hematocrit level should undergo an assessment before initiating warfarin and approximately every six months while on therapy. Other laboratory tests may be recommended based on the patient’s clinical presentation and INR result. Monitoring liver function, renal function, and occult blood may be indicated in certain patient populations.

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Reviewed by: Alisa Guzieva

Moderator: Iryna Kalikina

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