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See Also

Peripheral Artery Disease: causes and consequences

Coronary Artery Disease: causes and consequences

Vitamin K Antagonists

This section covers the role of vitamin K in coagulation, and discusses the limitations of using vitamin K antagonists as anticoagulants

Vitamin K antagonists

  • Vitamin K is essential for the synthesis of multiple factors in the coagulation cascade: Factors II (prothrombin), VII, IX and X, as well as protein C and protein S1
  • Antagonists of vitamin K have been used as anticoagulants for over 50 years
  • Warfarin, a synthetic derivative of coumarin, is the most commonly used VKA,1 although other coumarin derivatives (phenprocoumon and acenocoumarol) are also used


Limitations of vitamin K antagonists

  • Limitations of VKAs include:
    • Narrow therapeutic window
    • Interactions with drugs and food (e.g. foods rich in vitamin K)
    • Delayed onset and offset of anticoagulant effect (this is a particular limitation for prevention of venous thromboembolism, in which the duration of therapy is relatively short)
    • Need for frequent coagulation monitoring and dosage adjustments
    • Variable dose–response between individuals


Monitoring vitamin K antagonists

  • Because of the variability in the dose–response with VKA medications, monitoring the degree of anticoagulation is imperative
  • The prothrombin time (PT) is sensitive to changes in prothrombin, Factor VII, Factor IX and Factor X. Because of variability in the test reagent, thromboplastin, haematology laboratories now use an international INR for the measurement of PT prolongation2
    • The INR provides a standardized measure of the VKA anticoagulant effect and should be kept within a narrow range to control the intensity of anticoagulation in patients taking VKAs
    • For most conditions for which VKAs are prescribed, the recommended therapeutic INR range is 2.0–3.0
    • As the INR increases, the risk of bleeding increases, doubling with each one-point increase in INR
  • A patient’s INR should be monitored frequently when:2
    • A VKA is started
    • The dose is changed
    • There are changes in diet or medications known to interact with VKAs
  • Once a stable dose that produces a therapeutic INR level is reached, the test ideally should be repeated every 4 weeks2
  • Polymorphisms in the genes for cytochrome P450 2C9 (which is responsible for the metabolic clearance of warfarin) and vitamin K epoxide reductase (which recycles vitamin K) affect the pharmacodynamics of warfarin, contributing to a variable dose–response between individuals.3 Research is currently in progress on the clinical utility of genetic polymorphism testing to guide VKA dosing

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