💊 Warfarin

Warfarin is an oral anticoagulant belonging to the coumarin class. It acts as a vitamin K antagonist.

Warfarin inhibits vitamin K epoxide reductase, an enzyme essential for reactivating vitamin K. Vitamin K is a co-factor for the gamma-carboxylation of clotting factors II, VII, IX, and X, and anticoagulant proteins C and S. By depleting functional vitamin K, warfarin impairs the synthesis of these active clotting factors, thereby reducing the blood's ability to clot.

Warfarin is indicated for the prevention and treatment of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also used for stroke prevention in patients with atrial fibrillation (AF) and in those with prosthetic heart valves. Other indications include prevention of systemic embolism in patients with myocardial infarction.

Absolute contraindications include active bleeding, recent intracranial haemorrhage, severe uncontrolled hypertension, and severe hepatic impairment. Pregnancy is an absolute contraindication due to its teratogenic effects. Caution is required in patients with a high risk of bleeding, such as those with a history of GI bleeding or recent surgery.

The most significant adverse effect is bleeding, which can range from minor bruising to life-threatening haemorrhage (e.g., intracranial, gastrointestinal). Skin necrosis, often due to protein C deficiency, is a rare but serious complication. Other effects include nausea, diarrhoea, and skin rashes. Purple toe syndrome is a rare cholesterol embolisation phenomenon.

Regular monitoring of the International Normalized Ratio (INR) is essential to ensure therapeutic anticoagulation and minimise bleeding risk. The frequency of INR testing varies but is typically weekly initially, then every 2-12 weeks once stable. Liver function tests may be considered in patients with pre-existing hepatic impairment.

When prescribing, always check for active bleeding, recent haemorrhage, and pregnancy. Obtain a thorough medication history due to numerous drug interactions (e.g., antibiotics, NSAIDs, amiodarone) that can affect INR. Counsel patients extensively on the importance of regular INR monitoring, dietary vitamin K intake, and reporting any signs of bleeding.

Warfarin's vitamin K antagonism and its delayed onset of action are crucial. Remember the narrow therapeutic window and the importance of INR monitoring. Be aware of the many drug and dietary interactions that can affect INR. Its teratogenicity is a key point. Understand the management of bleeding and over-anticoagulation (e.g., vitamin K, prothrombin complex concentrate).

SBA questions frequently test the mechanism of action, particularly its interaction with vitamin K and the synthesis of clotting factors. Common themes include INR monitoring, factors affecting INR (diet, drugs), and management of over-anticoagulation or bleeding. Its contraindication in pregnancy and the risk of skin necrosis are also high-yield topics.