warfarin basics

7/30/2019 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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warfarin basics