Warfarin Flashcards
What class of drug is warfarin?
Anticoagulant (vitamin K antagonist)
Give 2 advantages of warfarin over DOACs
- Ability to directly monitor effect
- Ability to rapidly reverse its action
Give 3 disadvantages of warfarin compared to DOACs
- Higher incidence of major bleeding
- Diet & drug interactions
- Need for laboratory monitoring compared to DOACs
What is currently the only oral anticoagulant recommended for patients with aortic and mitral mechanical heart valves?
Warfarin
In which 3 conditions is warfarin the anticoagulation of choice?
- Mechanical heart valves
- Valvular atrial fibrillation
- End-stage renal failure
Give the mechanism of warfarin
- Inhibits vitamin KO reductase so limits the availability of vitamin K
- Vitamin K deficiency then reduces the coagulant activity of the blood by reducing the production of vitamin K dependent clotting factors (II, VII, IX, X and proteins C and S)
Which clotting factors are vitamin K dependent?
10, 9, 7 and 2
DOACs directly inhibit a single clotting factor. Which type of DOAC inhibits thrombin?
Dabigatran
Which types of DOAC inhibits FXa?
Rivaroxaban, apixaban and edoxaban
Why may warfarin be required in AF?
For prophylaxis of systemic embolisation
Why might warfarin be required in rheumatic heart disease?
for prophylaxis of systemic embolisation
What is rheumatic fever? Why does it increase risk of embolisation?
Rheumatic heart disease is a condition in which the heart valves have been permanently damaged by rheumatic fever (strep A/scarlet fever).
Clots can form in the damaged valves or enlarged heart.
Give 6 indications for warfarin
- Valvular atrial fibrillation
- Mechanical heart valves
- Rheumatic heart disease
- Mitral valve disease (irrespective of valve replacement)
- Treatment of VTE (2nd line to DOACs)
- Inherited, symptomatic thrombophilia
Why might warfarin be required in mitral valve disease?
Prophylaxis of systemic embolisation
Can warfarin be taken in pregnancy?
No - teratogenic (but safe in breastfeeding)
Give some contraindications for warfarin
- Pregnancy
- Malignancy/cancer
- Known hypersensitivity
- Haemorrhagic stroke
- Clinically significant bleeding
- Bleeding disordeer
- Uncontrolled severe hypotension
- Patient factors → repeated falls, uncooperative
- Drugs with increased risk of bleeding → NSAIDs, antiplatelets, enzyme inhibitors
How do NSAIDs affect warfarin?
- Displace warfarin from plasma albumin → potentiates effects
- Inhibit platelet function → increase bleeding risk
Give as many drugs as possible you can think of which may potentiate effects of warfarin
Enzyme inhibitors → think antibiotics!
- Ciprofloxacin
- Erythromycin/clarithromycin
- Miconazole
- Cranberry juice
- Oral contraceptives
Others → Antiplatelets (increase bleeding risk) & NSAIDs
Give as many drugs as possible you can think of which may decrease effects of warfarin
Enzyme inducers → think anti-epileptics!
- Carbamazepine
- Phenytoin
- St John’s Wort
- Alcohol
- Rifampicin
- Allopurinol
- Paracetamol
- SSRIs
- Lipid-regulating drugs
- Influenza vaccine
What are treatment targets for warfarin referred to in terms of ?
INR - international normalised ratio
What is the INR?
A laboratory measurement of how long it takes blood to form a clot used to determine the effects of oral anticoagulants on the clotting system.
It is a standardised version of the prothrombin time.
What is the prothrombin time?
The time taken for blood to clot via the extrinsic pathway.
What does a high INR mean?
Time to clot is longer (blood clots more slowly) → risk of bleeding
What does a low INR mean?
Time to clot is less (blood clots more quickly) → risk of clots
The majority of conditions treated with warfarin have a treatment target of INR 2-3. What is the one exception of this with a treatment target of INR 2.5-3.5?
Mechanical heart valves
Give some examples of conditions where the treatment target INR is 2-3
AF, VTE, mitral valve disease and inherited symptomatic thrombophilia
How long does warfarin treatment tend to be in patients with an unknown/permanent risk factor?
6 months or longer
How long does warfarin treatment tend to be in patients with no risk factors for developing clot (i.e. unprovoked)?
Lifelong
How long does warfarin treatment tend to be in patients with a known risk factor that is know no longer present?
3 months
How long may warfarin take to achieve an INR within the therapeutic range?
Up to 5 days
What does warfarin have the potential to cause in the first 5 days of treatment? Why?
A hypercoagulable state → due to the suppression of protein C occurs much more quickly than that of the coagulation factors due to protein C having a short half-life (approx. 8 hours)
What can be given alongside warfarin in the first 5 days of treatment?
Heparin
What is the most common side effect of warfarin?
Bleeding/haemorrhage (can be minor or life-threatening)
What must always be excluded in patients on warfarin following a head injury?
Intracranial haemorrhage
Give some other side effects of warfarin
- Hypersensitivity
- Rash
- Alopecia
- Warfarin induced skin necrosis
When would you consider reversing warfarin? (2 reasons)
- INR is supratherapeutic (i.e. blood clots not quickly enough - INR too low) → patient nleeding
- Prior to surgery
what are the 3 main options for warfarin reversal?
- Withholding warfarin
- Vitamin K (oral or IV)
- Prothrombin complex concentrate (PCC)
Why can PCC be given for warfarin reversal?
Contains vitamin K dependent clotting factors
Which enzyme system is warfarin metabolised by?
P450 in the liver
How do enzyme inducers affect warfarin levels?
Induce P450 system → warfarin metabolised more quickly → warfarin levels drop → efficacy decreased (INR low as blood clots more quickly)
How do enzyme inhibitors affect warfarin levels?
Inhibit P450 system → warfarin metabolised more slowly → warfarin levels rise → drug toxicity (INR high as blood clots more slowly) → bleed
Is clarithromycin an enzyme inhibitor or inducer?
Inhibitor
Is carbamazepine an enzyme inhibitor or inducer?
Inducer
Is alchol an enzyme inhibitor or inducer?
Inducer
Is phenytoin an enzyme inhibitor or inducer?
Inducer
How can the diet interact with warfarin?
As warfarin is an antagonist of vitamin K, consuming an excess of foods containing vitamin K may reduce warfarin’s efficacy so higher doses may be required to maintain therapeutic INR levels.
What diet advice should be given to patients taking warfarin?
Advise patients to maintain a regular, healthy diet and aim for a consistent intake of foods with high vitamin K levels e.g. green leafy vegetables
How does cranberry juice affect warfarin?
Cranberry juice/cranberries → Cranberries are an enzyme inhibitor for warfarin (increases its potency)
