Download - warfarin basics
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Basics of
Warfarin Management
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Objectives
Discuss warfarins mechanism of action
Review indications for warfarin and corresponding INR ranges
Differentiate between a prothrombin time (PT) and an
international normalized ratio (INR) Review most common side effects of warfarin
Summarize diet/drug/herbal interactions and other influences
on INR
Discuss important patient interview questions Describe how dosing adjustments are made and when to order
another INR
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Warfarin (Coumadin)
History
In 1939, bishydroxycoumarin was discovered from
spoiled sweet clover and found to have anticoagulant
properties In 1948, warfarin was discovered and used as an
effective rodenticide
In 1954, warfarin was approved by the FDA as a human
oral anticoagulant
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Warfarin (Coumadin)
Warfarin is an antagonist of the conversion of vitamin K
epoxide to vitamin K
Vitamin K is required for the synthesis of clotting factors (II,VII, IX, X) and endogenous anticoagulant proteins C and S
Without vitamin K, the rate at which these factors are
produced greatly decreases and produces a state ofanticoagulation
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Warfarin (Coumadin)
Pharmacodynamics/Pharmacokinetics
Each clotting factor differs in half-life
Longest is factor II (60 hours)
factor VII (5 hours) Shortest is protein C (8 hours)
Mean plasma half-life is approximately 40 hrs
Maximal effect of a dose occurs up to 48 hours after itis administered
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Common Indications for Warfarin
INR goal: 2-3 Prophylaxis of venous thrombosis for high risk surgery
Treatment of deep venous thrombosis (DVT)
Treatment of pulmonary embolism (PE)
Treatment of cardiac thrombus (i.e. mural)
Treatment of severe congestive heart failure (CHF)
Treatment of atrial fibrillation
Bioprosthetic heart valves (3 months post placement)
Hypercoagulable states (Protein C and S deficiency, Anti-thrombin III deficiency, Factor V Leiden)
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Common Indications for Warfarin
Goal INR 2.5-3.5 Mechanical Valves (exceptions St. Judes in the aortic position
with no other structural heart abnormalities 2-3 and caged-
ball/caged disk benefit from high level of anticoagulation)
Goal INR 3-4 Thrombus associated with antiphospholipid antibody
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Difference Between INR and PT
Prothrombin Time (PT)
Measure of time to clotting
Stimulated by thromboplastin (which comes from mammalian
tissue) Choice of thromboplastin can vary from lab to lab
International Normalized Ratio (INR)
Adjusts for the variable sensitivities of the different
thromboplastins The standard for evaluation of effect with coumadin therapy
INR = (PTpt/ PT ref)ISI
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Side Effects of Warfarin
Bleeding
Related to intensity, length of therapy, comorbidities, and
other medications
Risk dramatically increases when INR >4
Purple Toe Syndrome
Cholesterol microembolization
Occurs 3-10 weeks after initiation
Discontinuation is recommended
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Side Effects of Warfarin
Skin Necrosis
Associate with a thrombosis
Uncommon, occurs 3-8 days after initiation
More frequent in women and patients with protein C or S
deficiency
Discontinue, may reinitiate at low dose once heparin is
therapeutic
Teratogenic
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Diet Interactions
Food/herbs/vitamins/nutritional supplements which
contain vitamin K will decrease the effect of warfarin
In general, leafy green vegetables and oils containhigh amounts of vitamin K
Broccoli, brussels sprouts, cabbage, collard greens, endive, green
scallion, kale, lettuce, mustard greens, spinach, turnip greens,
watercress, large quantities of mayonnaise, canola, salad, and
soybean oils
Liver
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Diet Interactions
Patients do not have to cut all dark greens
out of their diet!
The key is consistency.
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Drug Interactions
Warfarin has many drug interactions which canmake the INR elevate or decrease
It is difficult to remember them all, so it is importantto look up every medication change that occurs andmanage appropriately
Starting a new drug Stopping an old drug
Increase/decrease in dose
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Drug Interactions
Advise patients not to take any aspirin (unless directedby their physician) or NSAIDs over the counter for pain,recommend Tylenol.
All other OTC medications should be reviewed withtheir physician/pharmacist before administering.
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Herbal/Nutritional Supplement
Interactions Always ask it a patient is taking herbals, they will
not always think about them as a medication
change. Many herbal interactions have occurred with
warfarin, but many are still unknown.
More frequent monitoring should be implemented
when they are initiated.
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Other influences on INR
Increase INR Compliance
Decreased Exercise Diarrhea
Fever
Hyperthyroidism
Hepatic Disorders
Prolonged hot weather
Vomiting
Decrease INR Compliance
Increased Exercise Edema
Hypothyroidism
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Important Interview Questions
Have you stopped your warfarin for any reason?
Any unusual bruising or bleeding?
Any unusual leg pain, chest pain, dizziness,numbness or tingling?
Any changes in you medications?
Any OTC or herbals started?
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Important Interview Questions
Any changes in your diet with regard to dark green
vegetables, oils, or liver?
Any missed doses?
How are you taking your warfarin?
What strength tablet do you have?
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Managing Warfarin Patients
Dosing adjustments
Look at trends and other causes for change in INR
Adjustments are made from 5-20% per week depending onclinical judgement
Patients should be monitored closely during initiation and
when the INR is not therapeutic.
Once therapeutic, may check weekly, q2week, q3week,
q4week after 2 consecutive INRs are in range.
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Vitamin K Administration
Vitamin K reverses the effects of warfarin
If INR < 5 without significant bleeding Rapid reversal is not necessary
Omit next dose and resume at lower dose
INR >5 and < 9 without significant bleeding Rapid reversal not necessary
Omit 1-2 doses
Could give 2.5mg Vit K orally and omit a dose
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Vitamin K Administration
INR > 9 without clinically significant bleeding 2.5 - 5mg Vit K orally and omit dose
If rapid reversal is required, due to serious bleeding
or INR > 20 Give 10mg Vit K IV
FFP
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Compliance
Obviously, the importance of compliance cannot be
over-looked!
Aids for compliance
Involvement of family
Pill boxes
Notebooks Alarm watches
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Resources
Managing Oral Anticoagulation Therapy - Clinical and
Operational Guidelines. 2nd edition Ansell, Oertel,
Wittkowsky. 2003, Aspen.
Anticoagulation Forum - www.acforum.org
www.coumadin.com
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Questions?