Warfarin
An oral vitamin K antagonist used to prevent stroke in atrial fibrillation, to treat and prevent venous clots and to protect replaced heart valves.
Drug card
- Class
- Vitamin K antagonist
- How it works
- Blocking vitamin K recycling, so the liver makes inactive clotting factors
- Used for
- Preventing stroke in atrial fibrillation
- Treating and preventing deep vein thrombosis
- Pulmonary embolism
- Preventing clots on replaced heart valves
- Known for
- Bleeding, which can be major or fatal
- Skin and tissue necrosis in the first days
- Birth defects (warfarin embryopathy)
Study it as a flashcard, and it comes back before you forget it.
Mechanism of action
How does warfarin work?
Inhibits VKORC1, the C1 subunit of the vitamin K epoxide reductase complex, so less working factor II, VII, IX, X, protein C and protein S is made. Its peak effect comes after 3 to 4 days. It is a racemic mix whose more potent S-form is cleared mainly by CYP2C9, so variants of CYP2C9 and VKORC1 change how much a person needs.
Uses
What is warfarin used for?
- Preventing stroke in atrial fibrillation
- Treating and preventing deep vein thrombosis
- Pulmonary embolism
- Preventing clots on replaced heart valves
- Fewer deaths, heart attacks and strokes after a heart attack
Side effects
Side effects of warfarin
- Bleeding, which can be major or fatalKnown forSerious
- Skin and tissue necrosis in the first daysKnown forSerious
- Birth defects (warfarin embryopathy)Known forSerious
- Purple toes syndrome (cholesterol microemboli)Serious
- CalciphylaxisSerious
- Acute kidney injury when the INR is too highSerious
- Hepatitis and raised liver enzymes
- Hair loss
- Allergic reactions, including hives
- Nausea and vomiting
- Taste change
- Rash, itching or dermatitis
Known for marks what an exam expects you to know it for.
Watch for
Cautions and what sets it apart
- Check the INR regularly (usual target 2.0 to 3.0); illness, diet changes, herbal products and new drugs can all shift it.
- Inhibitors of CYP2C9, CYP1A2 or CYP3A4 raise the INR and inducers lower it; NSAIDs and antiplatelet drugs add to bleeding.
- Contraindicated in pregnancy, except with mechanical heart valves at high clot risk; it causes embryopathy and fetal bleeding.
- Bleeding or a high INR: stop warfarin and give vitamin K1; prothrombin complex concentrate may be given when reversal is urgent.
Good to know: Taken by mouth, monitored by the INR and reversed with vitamin K; many drugs, herbal products and changes in diet shift its effect.
Remember it
A way to remember it
Warfarin works on 1972: factors 10, 9, 7 and 2.
X, IX, VII and II are the vitamin K-dependent clotting factors that warfarin leaves inactive. It also lowers the natural anticoagulants proteins C and S, and people short of protein C are the ones prone to warfarin skin necrosis.
A mnemonic widely used in teaching
Its class
Vitamin K antagonists
They block vitamin K epoxide reductase (VKORC1), so the liver cannot regenerate vitamin K from its epoxide. Without it, clotting factors II, VII, IX and X, as well as the natural anticoagulants proteins C and S, lose the gamma-carboxyglutamate residues they need to work. The effect builds over 3 to 4 days as the working factors already in the blood run down.
Easily mixed up with heparins and direct factor Xa inhibitors.
Sources
Checked against
Written for biofideX in plain words, after checking these references:
For learning pharmacology, not for treatment decisions: no doses are given, and a prescriber, pharmacist or the product's own label is the word on any one patient. Spotted a mistake? Tell us and we'll correct it.
Blood clots and cholesterol
Warfarin is one of 19 drugs practiced together here: their classes, how they work, what they treat and what they're known for.
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