Oral anti-coagulants - Warfarin

Question 1

What is warfarin used for?

Answer 1

1) DVT prophylaxis, recurrence and clot extension
2) atrial fibrilliation (prevent embolic stroke)
3) Heart valve replacement (prevent embolic stroke - short term for tissue valve replacement, long term for mechanical valve replacement)

Question 2

Why is warfarin not used to prevent arterial thrombosis?

Answer 2

Warfarin is not used to prevent arterial thrombosis as this is driven by platelet aggregation and is prevented by antiplatelet agents like aspirin and clopidogrel

Question 3

How does warfarin work?

Answer 3

• warfarin inhibits production of vitamin K dependant coagulation factors
• warfarin inhibits vitamin K epoxidase reductase —-> this prevents re-activation of vitamin K and therefore coagulation factor synthesis

Question 4

what are the adverse affects of warfarin?

Answer 4

• bleeding

e. g. from peptic ulcer

Question 5

what are the contraindications of warfarin?

Answer 5

• immediate risk of haemorrhage
• after trauma / before surgery
• liver disease ( so can’t metabolise drug)
• 1st trimester of pregnancy

Question 6

Why is warfarin contraindicated in the 1st trimester and towards the term of pregnancy

Answer 6

1) fetal abnormalities e.g. cardiac and cranial malformations with use in 1st trimester
2) massive haemorrhage in labour

Question 7

What are the drug interactions of warfarin?

Answer 7

Warfarin is activated by cytochrome P450 enzymes so any drug that induces this can enhance the efficacy of warfarin.
Cytchrome P450 inducers:
- phenytoin
- carbamezapine
- rifampicin

Cytochrome P450 inhibitors will reduce the effect of warfarin:

• fluconazole
• macrolids
• protease inhibitors

Question 8

What is the dose of warfarin on day one?

Answer 8

5-10mg orally

Question 9

What are the warfarin doses guided by?

Answer 9

International normalised ratio INR

Normal INR is less than 1.1

Therapeutic range of INR for warfarin = 2-3

Question 10

Why are LMW heparins started alongisde warfarin then stopped?

Answer 10

Warfarin takes several days for the anticoagulation effect to be achieved.
Patients who need immediate anticoag will be started on LMW heparin as well.
This LMW heparin will be stopped once INR achieved