Warfarin

Question 1

What is warfarin?

Answer 1

• Warfarin is an oral anticoagulant which 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 and protein C.

Question 2

What are the indications for warfarin?

Answer 2

• Venous thromboembolism: target INR = 2.5, if recurrent 3.5
• Atrial fibrillation, target INR = 2.5
• Mechanical heart valves, target INR depends on the valve type and location.
  
  • Mitral valves generally require a higher INR than aortic valves

Question 3

What factors may potentiate warfarin?

Answer 3

1. Liver disease
2. P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
3. Cranberry juice
4. Drugs which displace warfarin from plasma albumin, e.g. NSAIDs
5. Inhibit platelet function: NSAIDs

Question 4

What are the side effects of warfarin?

Answer 4

1. Haemorrhage
2. Teratogenic, although can be used in breastfeeding mothers
3. Purple toes
4. Skin necrosis:

• when warfarin is first started biosynthesis of protein C is reduced
• results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administratio
• Thrombosis may occur in venules leading to skin necrosis

Question 5

Name inducers of the P450 system - INR will decrease

Answer 5

1. Antiepileptics: phenytoin, carbamazepine
2. Barbiturates: phenobarbitone
3. Rifampicin
4. St John’s Wort
5. Chronic alcohol intake
6. Griseofulvin
7. Smoking (affects CYP1A2, reason why smokers require more aminophylline)

Question 6

Name inhibitors of the P450 system - INR will increase

Answer 6

• antibiotics: ciprofloxacin, clarithromycine/erythromycin
• isoniazid
• cimetidine,omeprazole
• amiodarone
• allopurinol
• imidazoles: ketoconazole, fluconazole
• SSRIs: fluoxetine, sertraline
• ritonavir
• sodium valproate
• acute alcohol intake
• quinupristin

Question 7

What do you when there is major bleeding?

Answer 7

1. Stop warfarin
2. Give intravenous vitamin K 5mg
3. Prothrombin complex concentrate - if not available then FFP*

*as FFP can take time to defrost prothrombin complex concentrate should be considered in cases of intracranial haemorrhage

Question 8

What do you do if INR > 8 + Minor bleeding ?

Answer 8

1. Stop warfarin
2. Give intravenous vitamin K 1-3mg
3. Repeat dose of vitamin K if INR still too high after 24 hours
4. Restart warfarin when INR < 5.0

Question 9

What do you if INR > + No bleeding?

Answer 9

1. Stop warfarin
2. Give vitamin K 1-5mg by mouth, using the intravenous preparation orally
3. Repeat dose of vitamin K if INR still too high after 24 hours
4. Restart when INR < 5.0

Question 10

What do you do if INR 5-8 and minor bleeding?

Answer 10

1. Stop warfarin
2. Give intravenous vitamin K 1-3mg
3. Restart when INR < 5.0

Question 11

What do you do if INR 5-8 and there is NO bleeding?

Answer 11

1. Withhold 1 or 2 doses of warfarin
2. Reduce subsequent maintenance dose