WAFARIN

Question 1

What is the main use of anticoagulants?

Answer 1

• To prevent thrombus formation or extension of an existing thrombus in the slower-moving venous side of the circulation
• The slower-moving venous side of the circulation has thrombus consisting of a fibrin web enmeshed with platelets and red cells

Question 2

Examples of oral AC

Answer 2

• Warfarin Sodium
• Acenocoumarol
• Phenindione
  They all antagonise the effect of vitamin K

Question 3

How long does it take for the anticoagulant effect to fully develop?

Answer 3

48-72 hours

Question 4

Which oral anticoagulant is the drug of choice?

Answer 4

Warfarin Sodium

Question 5

What should be determined at baseline? Does this affect the initial dose of Warfarin?

Answer 5

• The base-line prothrombin time should be determined
• BUT the initial dose SHOULD NOT be delayed whilst awaiting the result

Question 6

If INR is within 0.5 units of the target value…

Answer 6

This is generally satisfactory
Any larger deviations require dose adjustments

Question 7

Warfarin - maintain INR of 2.5

Answer 7

• VTE
• AF
• Cardioversion
• MI
• Cardiomyopathy

Question 8

Warfarin -Maintain INR of 3.5

Answer 8

Recurrent VTEs or mechanical heart valves

Question 9

How long should warfarin be taken for treatment of DVT/ PE?

Answer 9

1. 6 weeks for isolated calf-vein DVT
2. 3 months - VTE provoked by surgery
3. At least 3 months - unprovoked proximal DVT or PE

Question 10

Main adverse effect

Answer 10

Bleeding (haemorrhage)

Question 11

Antidote to bleeding

Answer 11

Phytomenadione (VK agonist)

Question 12

Major bleed

Answer 12

1. Stop warfarin
2. IV phytomenadione +
3. dried prothrombin complex

Question 13

INR >8, minor bleeding:

Answer 13

1. Stop warfarin
2. IV phytomenadione
3. Repeat doses of phyto if INR is still too high after 24hrs
4. Restart wafarin when INR is < 5

Question 14

INR >8, no bleeding:

Answer 14

1. Stop warfarin
2. PO phytomenadione
3. Repeat doses of phyto if INR is still too high after 24hrs
4. Restart wafarin when INR is < 5

Question 16

INR 5-8, minor bleeding

Answer 16

Stop warfarin - IV phytomenadione

Question 17

INR 5-8, no bleeding:

Answer 17

Withhold 1-2 doses of warfarin

Question 18

When should you restart warfarin?

Answer 18

Restart warfarin when INR <5

Question 19

How often should INR be monitored?

Answer 19

INR should be monitored every 1-2 days in early treatment, and then every 12 weeks

Question 20

Warfarin - surgery where there is a risk of severe bleeding:

Answer 20

• Stop warfarin 3-5 days before
• Give phyto if INR is >1.5 the day before surgery

Question 21

High risk of VTE when undergoing surgery

Answer 21

bridge with LMWH → stop LMWH 24 hours before surgery → restart LMWH 48 hours after

Question 22

Warfarin - emergency Surgery

Answer 22

• If can be delayed by 6-12 hours: IV Vitamin K
• If can’t be delayed by 6-12 hours: IV Vitamin K + dried prothrombin complex

Question 23

Which antiplatelet has a higher risk of bleeding in combo with warfarin?

Answer 23

Clopidogrel
- aspirin + warfarin have risk of bleeding, but it’s lower

Question 24

Warfarin - side effects

Answer 24

MHRA Warning: SKIN NECROSIS AND CALCIPHYLAXIS
- Painful skin rash
Haemorrhage: Prolonged Bleeding
- Vitamin K1 (phytomenadione) antidote

Question 25

CI

Answer 25

- AVOID use within 48 hours post-partum (giving birth) - Haemorrhagic stroke - Significant bleeding - pregnancy

Question 26

Can Vitamin K antagonist be used in pregnancy?

Answer 26

- AVOID in pregnancy - Warfarin, acenocoumarol and phenindione cross the placenta with a risk of congenital malformations, and placental, fetal or neonatal haemorrhage

Question 27

What is the dose of warfarin?

Answer 27

Initially: - 5-10mg daily on day 1 - Subsequent doses depend on prothrombin time - a lower dose may be given to those who do not require rapid anticoagulation - Elderly require a lower induction dose

Question 28

How often to administer warfarin?

Answer 28

- once a day in the evening - same time of the day - preferably on an empty stomach

Question 29

What happens if you forget a dose of warfarin?

Answer 29

- do NOT double up! - take it as soon as you remember and let the clinic team know!

Question 30

Interactions

Answer 30

- Amiodarone - increases plasma concentration - Azathioprine reduces the anticoagulant effect - Antifungals (Azoles e.g. Miconazole) increases anticoagulant effect - Carbamazepine reduces plasma concentration - Corticosteroids may induce or enhance the anticoagulant effect - Metronidazole increases anticoagulant effect - NSAIDs may enhance the anticoagulant effect - Phenytoin reduces the anticoagulant effect - Rifampacin decreases anticoagulant effect - Statins (Fluvastatin, Rosuvastatin) increases the anticoagulant effect of warfarin

Question 31

What's the easiest way to determine interaction with warfarin with regards to cytochrome enzymes?

Answer 31

Warfarin is metabolised by Cytochrome P450 enzymes, so any enzyme inducers/ inhibitors will affect its metabolism & thus INR, so the dose may need to be adjusted

Question 32

Warfarin diet & alcohol interactions

Answer 32

- Alcohol (in those who drink heavily) can potentially decrease the anticoagulant effect of coumarins - Pomegranate can increase INR in warfarin and acenocoumarol - Cranberry juice can increase the anticoagulant effect of warfarin - Avoid large amounts of green vegetables and green tea

Question 33

Which fruits should you avoid whilst on warfarin?

Answer 33

- grapefruit juice - cranberry juices - Pomegranate - mango juices - mangoes - Seville oranges

Question 34

Which anticoagulant discolours urine pink or orange?

Answer 34

Phenindione