Warfarin Starting Dose | Dosing Initiation Protocol

Oral anticoagulants especially warfarin are used in most hospitals to decrease the risk of systemic arterial thromboembolism including strokes in patients with atrial fibrillation or flutter or prosthetic valves (Ebell MH, 2005). It is also indicated to prevent recurrent venous thromboembolism in patients with deep vein thrombosis and pulmonary embolism. Besides, it may be used as secondary prevention after myocardial infarction. Over the last 10 years, the use of warfarin has increased substantially particulary within the context of an ageing population (Fitzmaurice DA, 2005).

The INR (International Normalised Ratio) was developed in response to variation in thromboplastin sensitivity and different ways of reporting the prothrombin time across the world. Inappropriate management of anticogulation therapy can lead to subtherapeutic or supratherapeutic INR values which lead to increasing risk of acute or recurrent thromboembolic episodes or bleeding episodes respectively. For most indications, the therapeutic range of INR would be between 2.0 and 3.0. Though, there are exceptions when warfarin is used for secondary prevention after myocardial infarction or for patients with high-risk mechanical prosthetic heart valves, in which case the range would be 2.5 to 3.5 (Heneghan C, Tyndel S et al, 2010).

When starting anticoagulation therapy, it is crucial to review and weight the benefits and potential risks to the patient during therapy. Initial dose of warfarin is typically 5 mg/day in most patients (Ageno W, Steidl L et al, 2003). However, a starting dose of less than 5 mg may be considered for patients greater than 70 years of age, elevated baseline INR greater than 1.1, hypoalbuminemic patients including malnourished, liver disorders, post-operative and others, impaired nutrition (weight < 45 kg), heart failure, known to take medications that increase sensitivity of warfarin, or either induce or inhibit excretion of warfarin (Garcia D, Regan S et al, 2005).

The loading dose for initiation of warfarin has changed from time to time over the years to provide the most effective dose to the patient without compromising the initiation period. Recently, the loading dose was suggested to be 5 mg of starting dose which is close to the average maintenance dose was at least as effective at producing a therapeutic anticoagulation effect by day 4 to 5 as a 10-mg loading dose. In addition, the 5-mg loading dose was associated with lower frequency of unwanted hypocoagulability than the 10-mg dose (Crowther MA, Ginsberg JB et al, 1999).