Warfarin

Question 1

What are indications for the use of warfarin?

Answer 1

• DVT
• PE
• AF
• Valve replacement

Question 2

Is warfarin used to treat arterial thrombosis?

Answer 2

No - antiplatelet agents such as aspirin and clopidogrel are used for this

Question 3

What is the mechanism of action of warfarin?

Answer 3

Inhibits hepatic production of vitamin K-dependent coagulation factors and cofactors. Vitamin K must be in its reduced form for synthesis of coagulation factors. It is then oxidised during the synthetic process.

An enzyme called vitamin K epoxide reductase reactivates oxidised vitamin K. Warfarin inhibits vitamin K epoxide reductase, preventing reactivation of vitamin K and coagulation factor synthesis

Question 4

What are the main adverse reactions that can occur with warfarin use?

Answer 4

Bleeding

Question 5

What contraindications would you want to check for in someone you are about to start on warfarin?

Answer 5

• Severe bleeding risk
• Active bleeding
• Pregnancy - First trimester

Question 6

Why should warfarin not be used in the first trimester of pregnancy?

Answer 6

Can cause foetal growth abnormalities

Question 7

What are important interactions that you should be aware of when giving someone warfarin?

Answer 7

Cytochrome P450 inhibitors - decrease metabolism, increasing bleeding

• Macrolides
• Fluclonazole
• Protease inhibitors

Cytochrome P450 inducers - increase metabolism, decreasing bleeding

• Phenytoin
• Rifampicin
• Carbemazepine

Antibiotics - kill gut flora which synthesise vitamin K

Question 8

What should you consider doing when starting someone on warfarin?

Answer 8

Start a LMWH in tandem to cover increase in clotting risk

Question 9

How long should LMWH be administered for when commencing someone on warfarin therapy?

Answer 9

5 days + adequate INR is reached for 24 hours (i.e. 2 INR’s 24 hours apart)

Question 10

What does warfarin increase clotting risk initially?

Answer 10

Warfarin inhibits the natural anticoagulant activity of proteins C and S, and it does this before inhibiting the other clotting factors

Question 11

What should you do before commencing someone on warfarin therapy?

Answer 11

• Obtain pre-treatment INR
• Determine and record target INR
• Record therapeutic indication

Question 12

What dose of warfarin would you commence someone on?

Answer 12

2mg daily

Question 13

When after commencing warfarin therapy would you check INR?

Answer 13

Day 3 and 7

Question 14

If INR on warfarin therapy was between 3.0-4.0 7 days after initiation of treatment, what would you do?

Answer 14

Reduce from 2 mg to 1.5 mg, and check INR after 3 days

Question 15

What is the recommended INR and INR range for treating someone with a PE?

Answer 15

2.5 - Range 2.0-3.0

Question 16

What INR and INR range is recommended for the treatment of DVTs?

Answer 16

2.5 - range 2.0-3.0

Question 17

What INR and INR range would you use when treat AF?

Answer 17

2.5 - range 2.0-3.0

Question 18

What INR and INR range would you aim for someone with a mechanical heart valve?

Answer 18

3.5 - range 3.0 - 4.0

Question 19

How is warfarin taken?

Answer 19

Once daily tablet - usually in the evening

Question 20

How long is warfarin usually taken for in DVT?

Answer 20

3 months - unprovoked

Question 21

How long is warfarin usually prescribed for in a PE?

Answer 21

6 months

Question 22

How is regularity of checks at the INR clinic determined?

Answer 22

Based on INR stability

Question 23

What advice would you give someone regarding warfarin side effects?

Answer 23

• Bleeding - seek advice for head injury, prolonged nose bleed, unusual headache, blood in urine/stool/vomit, unexplained severe bruising
• Diarrhoea, rash, hair loss, nausea
• Can affect/be affected by other drugs - watch out

Question 24

What should those on warfarin avoid?

Answer 24

Avoid - liver, spinach, cranberry juice, alcohol binges, NSAIDs