Warfarin

Warfarin is taken by mouth to inhibit vitamin K. This vitamin is essential for effective production of clotting factors II, VII, IX, X, and anticoagulant proteins C&S. Warfarin is given once daily. It is monitored by the prothrombin time and the international normalized ratio (INR).

Warfarin is a narrow therapeutic index drug (NTI). When the INR falls below 2.0 thrombosis risk increases and when the INR rises above 4.0 serious bleeding risk increases.

Duration of Action

Warfarin takes 4-7 days to have its optimum effect. Large loading doses do not markedly shorten the time to achieve a full therapeutic effect but cause rapid falls in the level of protein C, which may precipitate paradoxical thrombosis in the first few days of warfarin therapy. The following general recommendations for warfarin use are made.

• Initiate therapy with the estimated daily maintenance dose (2-5 mg.).
• Elderly or debilitated patients often require low daily doses of warfarin (2-4 mg.).
• Patients are confused by alternating daily doses (e.g. 7.5 and 5.0 mg).
• Significant changes in INR can usually be achieved by small changes in dose (15% or less).
• 4-5 days are required after any dose change or any new diet or drug interaction to reach the new antithrombotic steady state.

Frequency of Dosing

Daily

Monitoring

Warfarin is monitored by the one stage prothrombin time. Prothrombin times are reported in seconds, as a ratio of the prothrombin time in seconds to the mean normal prothrombin time of the laboratory, and as the international normalized ratio (INR). The INR is the most reliable way to monitor the prothrombin time.

Remember: Drug interactions with warfarin are not always known or predictable. Repeat an INR 5-7 days after adding, subtracting or changing the dose of any drug in a patient receiving warfarin.

 

Dietary And Other Interactions With Warfarin

Patients taking warfarin should eat a diet that is constant in vitamin K.

• Minimize changes in intake of green leafy vegetables (spinach, greens, and broccoli), green peas, and oriental green tea.

Conditions that interfere with vitamin K uptake or interfere with liver function will increase the warfarin effect.

• Expect a longer prothrombin time in patients with CHF, jaundice, hepatitis, liver failure, diarrhea, or extensive cancer or connective tissue disease.
• Expect a longer prothrombin time when patients receiving warfarin are hospitalized for any reason.

Metabolic alterations can affect the prothrombin time.

• Expect a longer prothrombin time in patients with hyperthyroidism or high fever.
• Expect a shorter prothrombin time in patients with hypothyroidism.

Initiating Warfarin Therapy

Are there any contra-indications?

1. Pregnancy
   
2. History of warfarin-induced purpura
   
3. Active Bleeding

Has the patient been instructed on drug interactions and a diet of constant vitamin K intake?

Has a baseline PT, APTT, and platelet count been obtained?

** Starting on day 3, adjust subsequent doses as outlined below based on INR. Obtain INR 3-4 times in week 1; twice in 2nd week; then weekly until stable; then monthly. Elderly or debilitated patients often require low daily doses of warfarin (2-3 mg).

Initiating Therapy: Dose Adjustment

Stable Patients: Dosing Algorithm To Achieve INR Of 2.0 - 3.0

Warfarin Sodium¹: Monitoring and Dosage Adjustment in Stable Anticoagulated Patients (based on a starting dose of 4 mg/d)

¹ - Coumadin®, 1mg tablet

² - INR: International Normalized Ratio = (x/y)^z , where:

x = Prothrombin Time of sample (sec)

y = Mean Normal Prothrombin Time (sec)

z = [ ISI of Thromboplastin]

 

Evaluation Of Atrial Fibrillation

Atrial fibrillation on ECG (constant or intermittent)
Obtain history and physical exam (valvular, ischemic or hypertensive heart disease present? Diabetes or thyrotoxicosis present?)
Obtain surface echocardiogram (valvular heart disease, atrial or appendegeal thrombus or LV dysfunction present?)
Valvular, ischemic, or hypertensive heart disease present; diabetes, previous stroke or TIA present; or patient 65 years or older.		Thrombosis? Consider TEE		No heart, or systemic disease detected and patient less than 65 Years old.
Anticoagulate with Warfarin to INR of 2.0-3.0				No anticoagulation ("Lone atrial fibrillator")

If low intensity anticoagulation contraindicated, aspirin at 325 mg daily may offer some benefit, but warfarin has performed better in most comparisons to aspirin.