What is the action and thromboprophylaxis of Warfarin (Coumadin)?

From the Guidelines

Warfarin is an oral anticoagulant that prevents blood clot formation by inhibiting vitamin K-dependent clotting factors (II, VII, IX, and X) and proteins C and S, and its use for thromboprophylaxis should be guided by the most recent evidence, which recommends a target International Normalized Ratio (INR) of 2.0-3.0 for most indications, as supported by the study published in 2017 1.

Action of Warfarin

Warfarin works by preventing the synthesis of new clotting factors rather than affecting existing ones, which is why it takes 5-7 days to reach full anticoagulant effect. The typical starting dose is 5mg daily, though elderly patients or those with liver disease may start at 2-3mg daily. Dosing is then adjusted based on the INR, with target ranges typically between 2.0-3.0 for most indications and 2.5-3.5 for mechanical heart valves.

Thromboprophylaxis with Warfarin

Warfarin is primarily used for thromboprophylaxis in conditions such as atrial fibrillation, mechanical heart valves, deep vein thrombosis, and pulmonary embolism. The choice of antiplatelet therapy or warfarin for long-term anticoagulation depends on the relative risk for thromboembolism and an assessment of a patient’s ability to be compliant with the regimen, as noted in the study published in 2013 1.

• The target INR is 2.0 to 3.0, except for patients with recurrent thromboembolism on warfarin and those with mechanical prosthetic valves, who may require a higher target INR of 2.5 to 3.5, as recommended by the study published in 2003 1.
• Warfarin requires regular INR monitoring, initially twice weekly until stable, then extending to monthly once the therapeutic range is consistently maintained.
• Food interactions are significant, particularly with vitamin K-rich foods like leafy greens, which can reduce warfarin's effectiveness.
• Numerous drug interactions exist that can potentiate (antibiotics, amiodarone) or reduce (barbiturates, carbamazepine) warfarin's effect.
• Patients should be educated about bleeding risks, the importance of consistent vitamin K intake, and the need to inform all healthcare providers about their warfarin use.
• Bridging with heparin or low molecular weight heparin may be necessary when initiating therapy or during procedures, as warfarin takes 5-7 days to reach full anticoagulant effect, as noted in the study published in 2009 1.

Considerations for Warfarin Use

The use of warfarin therapy can be particularly challenging for clinicians and patients in certain settings, such as in patients with cancer, due to the increased risk of bleeding and the potential for interactions with chemotherapeutic agents, as highlighted in the study published in 2009 1.

• The risk of bleeding is a significant concern, and patients should be closely monitored for signs of bleeding.
• The use of warfarin in patients with cancer requires careful consideration of the potential benefits and risks, and alternative anticoagulants may be preferred in certain situations.
• The management of warfarin therapy in patients with cancer should be individualized, taking into account the specific clinical context and the patient's underlying condition.

From the FDA Drug Label

Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets and other coumarin anticoagulants act by inhibiting the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide The action of Warfarin (Coumadin) is to inhibit the synthesis of vitamin K dependent clotting factors. The thromboprophylaxis of Warfarin (Coumadin) is to prevent venous thrombosis, pulmonary embolism, and thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement 2. Key points about the action and thromboprophylaxis of Warfarin (Coumadin) include:

• Inhibition of vitamin K dependent clotting factors
• Prevention of venous thrombosis and pulmonary embolism
• Prevention of thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement
• Interference with clotting factor synthesis by inhibition of the VKORC1 enzyme complex 2

From the Research

Action of Warfarin

• Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation 3
• It works by inhibiting the production of vitamin K-dependent clotting factors in the liver, thereby preventing the formation of blood clots
• The common indications for warfarinisation are atrial fibrillation, venous thromboembolism, and prosthetic heart valves 4

Thromboprophylaxis of Warfarin

• Warfarin is used as thromboprophylaxis in patients with mechanical heart valves to prevent valve thrombosis and thromboembolism 5, 6
• The target international normalized ratio (INR) for warfarin therapy is typically between 2.0 and 3.0 6, 7
• Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation, but the absolute reduction in stroke rate by warfarin is small 3
• The use of warfarin requires careful monitoring of INR levels to minimize the risk of bleeding complications 4, 7
• Alternative anticoagulation therapies, such as enoxaparin or apixaban, may be considered for patients who do not tolerate or who fail warfarin therapy 5, 6