Warfarin

Question 1

What is the mechanism of action of warfarin?

Answer 1

Inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.

Question 2

What are the indications for warfarin?

Answer 2

• Venous thromboembolism
• Atrial fibrillation
• Mechanical heart valves

Question 3

What is the target INR for patients being treated for venous thromoembolism?

Answer 3

Target INR = 2.5, if recurrent 3.5

Question 4

What is the target INR for patients being treated for atrial fibrillation?

Answer 4

Target INR = 2.5

Question 5

What is the INR?

Answer 5

International Normalised Ratio = The ratio of the prothrombin time for the patient over the normal prothrombin time

Question 6

What are the side-effects of warfarin?

Answer 6

• Haemorrhage
• Teratogenic (but can be used in breastfeeding mothers)
• Skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis
• Purple toes

Question 7

How do you adjust the warfarin for a patient with major bleeding?

Answer 7

• Stop warfarin
• Give intravenous vitamin K 5mg
• Prothrombin complex concentrate - if not available then FFP

Question 8

When should warfarin be stopped before surgery?

What should their target INR be before surgery

Answer 8

5 days

Target INR < 1.5

Question 9

What advice would you give on Vitamin K when commencing a patient on warfarin?

Answer 9

Foods rich in Vitamin K (such as kale, brocolli, brussel sprouts & spinach) should be avoided in excess & should be kept in eaten in consistent amounts from week to week.

Question 10

What general factors can increase the action of warfarin?

Answer 10

• Liver disease
• P450 enzyme inhibitors
• Cranberry juice
• Drugs which displace warfarin from plasma albumin
  
  • e.g. NSAIDs
• Drugs that inhibit platelet function
  
  • e.g. NSAIDs

Question 11

What factors induce the P450 system in the liver?

Answer 11

• Antiepileptics (e.g. phenytoin, carbamazepine)
• Barbiturates (e.g. phenobarbitone)
• Rifampicin
• St John’s Wort
• Chronic alcohol intake
• Griseofulvin
• Smoking (affects CYP1A2, reason why smokers require more aminophylline)

Question 12

What effect on INR do inducers of the P450 system have?

Answer 12

The reduce the INR

Question 13

What effect on INR do P450 inhibitors have?

Answer 13

Increase INR

Question 14

Give examples of factors that inhibit the P450 system.

Answer 14

• Antibiotics (e.g. ciprofloxacin, clarithromycine/erythromycin)
• Isoniazid
• Cimetidine/omeprazole
• Amiodarone
• Allopurinol
• Imidazoles (e.g. ketoconazole, fluconazole)
• SSRIs (e.g. fluoxetine, sertraline)
• Ritonavir
• Sodium valproate
• Acute alcohol intake
• Quinupristin

Question 15

What PT & APTT results are expected from a patient on warfarin?

Answer 15

Prolonged PT

Normal APTT

Question 16

Is warfarin safe to continue in a patient with AKI?

Answer 16

Yes