Warfarin pharmacology, monitoring and reversal
How warfarin blocks vitamin K recycling, why the INR rises before the patient is protected, how the INR is calculated, the CYP2C9 and VKORC1 sources of variability, and Australian reversal with four-factor PCC (Beriplex) and vitamin K.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Warfarin inhibits VKORC1, stopping recycling of vitamin K epoxide. Factors II, VII, IX, X and proteins C and S are made uncarboxylated and inactive.
- It has no effect on factors already circulating, so onset depends on factor half-lives. The INR rises with factor VII on day 2; protection waits for prothrombin over 5 or more days.
- Racemic, 99% albumin bound, half-life about 40 hours. S-warfarin (CYP2C9) carries most of the effect.
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Sources
- 2025 ESC Guidelines for the management of cardiovascular disease and pregnancyEuropean Heart Journal, 2025
- 2024 ESC Guidelines for the management of atrial fibrillationEuropean Heart Journal, 2024
- Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range (ACTIVE W)Circulation (Connolly et al., 2008;118:2029-37), 2008
- Updated recommendations for warfarin reversal in the setting of four-factor prothrombin complex concentrateAU/NZMedical Journal of Australia (Robinson, McFadyen, Merriman, Tan, Baker and Tran, 2025;222:49-51), 2025
- Warfarin reversalAU/NZAustralian Red Cross Lifeblood, 2025
- A non-canonical vitamin K cycle is a potent ferroptosis suppressorNature (Mishima et al., 2022;608:778-83), 2022
- An update of consensus guidelines for warfarin reversalAU/NZMedical Journal of Australia (Tran, Chunilal, Harper, Tran, Wood and Gallus, 2013;198:198-9), 2013
- Therapeutic Guidelines: CardiovascularAU/NZTherapeutic Guidelines Ltd
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th ed.)McGraw Hill (Brunton and Knollmann, 2023), 2023
- Last updated
- 14 November 2026
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