WAFARIN Flashcards
What is the main use of anticoagulants?
- 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
Examples of oral AC
- Warfarin Sodium
- Acenocoumarol
- Phenindione
They all antagonise the effect of vitamin K
How long does it take for the anticoagulant effect to fully develop?
48-72 hours
Which oral anticoagulant is the drug of choice?
Warfarin Sodium
What should be determined at baseline? Does this affect the initial dose of Warfarin?
- The base-line prothrombin time should be determined
- BUT the initial dose SHOULD NOT be delayed whilst awaiting the result
If INR is within 0.5 units of the target value…
This is generally satisfactory
Any larger deviations require dose adjustments
Warfarin - maintain INR of 2.5
- VTE
- AF
- Cardioversion
- MI
- Cardiomyopathy
Warfarin -Maintain INR of 3.5
Recurrent VTEs or mechanical heart valves
How long should warfarin be taken for treatment of DVT/ PE?
- 6 weeks for isolated calf-vein DVT
- 3 months - VTE provoked by surgery
- At least 3 months - unprovoked proximal DVT or PE
Main adverse effect
Bleeding (haemorrhage)
Antidote to bleeding
Phytomenadione (VK agonist)
Major bleed
- Stop warfarin
- IV phytomenadione +
- dried prothrombin complex
INR >8, minor bleeding:
- Stop warfarin
- IV phytomenadione
- Repeat doses of phyto if INR is still too high after 24hrs
- Restart wafarin when INR is < 5
INR >8, no bleeding:
- Stop warfarin
- PO phytomenadione
- Repeat doses of phyto if INR is still too high after 24hrs
- Restart wafarin when INR is < 5
INR 5-8, minor bleeding
Stop warfarin - IV phytomenadione
INR 5-8, no bleeding:
Withhold 1-2 doses of warfarin
When should you restart warfarin?
Restart warfarin when INR <5
How often should INR be monitored?
INR should be monitored every 1-2 days in early treatment, and then every 12 weeks
Warfarin - surgery where there is a risk of severe bleeding:
- Stop warfarin 3-5 days before
- Give phyto if INR is >1.5 the day before surgery
High risk of VTE when undergoing surgery
bridge with LMWH → stop LMWH 24 hours before surgery → restart LMWH 48 hours after
Warfarin - emergency Surgery
- 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
Which antiplatelet has a higher risk of bleeding in combo with warfarin?
Clopidogrel
- aspirin + warfarin have risk of bleeding, but it’s lower
Warfarin - side effects
MHRA Warning: SKIN NECROSIS AND CALCIPHYLAXIS
- Painful skin rash
Haemorrhage: Prolonged Bleeding
- Vitamin K1 (phytomenadione) antidote
CI
- AVOID use within 48 hours post-partum (giving birth)
- Haemorrhagic stroke
- Significant bleeding
- pregnancy
Can Vitamin K
antagonist be used in pregnancy?
- AVOID in pregnancy
- Warfarin, acenocoumarol and phenindione cross the placenta with a risk of congenital malformations, and placental, fetal or neonatal haemorrhage
What is the dose of warfarin?
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
How often to
administer warfarin?
- once a day in the evening
- same time of the day
- preferably on an empty stomach
What happens if you forget a dose of warfarin?
- do NOT double up!
- take it as soon as you remember and let the clinic team know!
Interactions
- 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
What’s the easiest way to determine interaction with warfarin with regards to cytochrome enzymes?
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
Warfarin diet & alcohol interactions
- 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
Which fruits should you avoid whilst on warfarin?
- grapefruit juice
- cranberry juices
- Pomegranate
- mango juices
- mangoes
- Seville oranges
Which anticoagulant discolours urine pink or orange?
Phenindione
