Warfarin blocks Vitamin K. This reduce the level of clotting factors II, VII, IX and X, the extrinsic clotting pathway.
It prolongs the prothrombin time.This makes people bleed! The pathophysiology is nicely summarised by the Calgary Guide.
Things that increase INR
- antibiotics, NSAIDs, amiodarone, steroids, thyroxine, phenytoin (unpredictable effect), propranolol, statins
- liver failure, heart failure, increased metabolic rate - eg thyrotoxicosis, illness, old age
Things that decrease INR- carbamazepine, rifampicin, OCP, vitamin K supplements, barbiturates, herbal remedies
- dietary vitamin K including avocado, leafy green vegetables
General Warfarin Things for Us to Consider
I know we should never have to dose warfarin in the ED...but we do, because we're turning in to a ward. Remember:
Any change in warfarin dose will have no effect for 16 hours
Maximum effect is not seen for up to 60 hours
INR fluctuates - do not change from a stable dose because of one "slightly off" INR
Small changes in dose can result in large changes in INR - do not overcompensate
If you change a dose, try to stick with it for at least 2 days before changing it again
Consider drug interactions, especially antibiotics and steroids
Any change in the patient’s condition can affect the INR - in particular, worsening liver or cardiac function can dramatically increase the INR
Only check INR daily if the INR is very high or the patient is clinically unstable
- Major bleeding or the requirement for immediate reversal - prothombin complex concentrate and 10 mg IV vitamin K
If giving beriplex, recheck the INR 20minutes later.
Octaplex weight dependent
Beriplex INR dependent
- Minor bleeding - 1-3 mg IV vitamin K
Intravenous (IV) vitamin K works within 6 hours whereas oral vitamin K works completely within 12 hours.
2mg of the IV vit K preparation given PO is the best way to lower an INR and starts to work within six hours
5 or 10mg vit K reverses everything completely.
- INR >8.0 with no bleeding - 1-5 mg oral vitamin K
- INR 5.0-8.0 - warfarin should be withheld unless seen as very high risk of bleeding then vitamin K should be used
Remember, warfarin lasts longer than most clotting factors.