Wafarin at the correct doses it is a very useful medicine. Warfarin is an anticoagulant it helps to prevent blood clots. This is important in people prone to blood clots, such as patients with damaged heart valves clots in the veins or people in Atrial Fibrillation (an abnormal heart rhythm). As more and more research confirms the effectiveness of Warfarin more and more patients will be prescribed this medication

Risks and benefits of warfarin

There are many indications for warfarin therapy. The decision to start warfarin depends on an assessment of each patient’s balance between the harmful effects and the benefits of anticoagulation.

The common indications for warfarin therapy

Supported with good evidence • prosthetic valve replacement • deep vein thrombosis within the last three months • pulmonary embolism within the last six months • recurrent deep vein thrombosis or pulmonary embolism • atrial fibrillation associated with valvular heart disease • atrial fibrillation without structural heart disease in patients >50-65 years old • embolic stroke

Supported but limited evidence • congestive heart failure or dilated cardiomyopathy

Little or no supporting evidence • non-embolic cerebrovascular disease • peripheral vascular disease

If the dose of warfarin is too high it may thin the blood too much. If the dose is too low it may not prevent clots forming. The dose required to do the job depends on the indication for treatment but also varies from person to person and from time to time. To prevent complications people taking warfarin need regular blood tests. You should record the results of these INR (International Normalised Ratio) tests and the dose of warfarin you take

A patient’s risk of bleeding is greatest in the first few months after starting warfarin. Bleeding complications occur in 3-10% of patients on warfarin per year, and while most bleeds are minor some can threaten life. Although the bleeding risk increases as the INR increases, 50% of bleeding episodes occur while the INR is less than 4.0 and bleeding complications can still occur with INR in the target range. Warfarin should be continued only for as long as the risk of thrombosis exceeds the risk of serious bleeding

Warfarin therapy is usually life-long in patients with mechanical heart valves, while a patient with their first DVT in the post-operative setting may warrant only 3 months of warfarin therapy

Risk factors for major bleeding in patients on warfarin

Marked increase in risk • age >70 years old • bleeding disorder • gastrointestinal haemorrhage within the last 18 months • previous stroke • liver disease • history of falls

Moderate increase in risk • age 60-70 years • chronic renal failure • change in interacting medications • change in, or poor, nutrition • first three months of warfarin therapy • large fluctuations in INR

White RH, Beyth RJ, Zhou H, Romano PS. Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 1999;107:414-24

Age is one of the strongest risk factors for bleeding. In one study, the annual risk of major bleeding was 2.9% for patients older than 70 years, while no major bleeds occurred in patients under 50 years old.

Major bleeding is defined as: if it was fatal, involved the brain, behind the eye, involved a joint, required surgery, led to a haemoglobin fall of 2 g/dL or more, and/or required the transfusion of two or more units of blood.

Warfarin in pregnancy can cause serious birth defects and causes bleeding in mother and child, so it is generally not prescribed in pregnancy. Warfarin can be taken during breast feeding if required

Starting Warfarin

It is now recommended that therapy start with a dose based on your age unless you are on medications known to affect Warfarin dose

Average Warfarin dose by age
Age	Average Warfarin Dose
<50y 50–60y 60–70y 70–80y 80–90y	6.0 mg 5.0 mg 4.5 mg 4.0 mg 3.5 mg

Warfarin is best taken at the same time each day, traditionally 6 pm, but ideally at a time when you are most likely to remember to take it. There are two brands of Wafarin, Coumadin and Mavaran. The doses of these brands are not necessarily equivalent and you should stick to one brand or the other

While Warfarin may be used in rat poison, nobody measures the dose and performs regular blood tests on rats! To minimise the risks of Warfarin and receive its full benefits we need to adjust the dose of wafarin to specific INR targets ranges

Range of International Normalised Ratio (INR)  recommended for specific indications for warfarin therapy
Condition	INR range
Preventing DVT (Deep Vein Thrombosis) (high-risk patients, like those who have had hip replacement) Therapy after DVT or pulmonary embolism Preventing systemic embolism Atrial fibrillation Valvular heart disease After myocardial infarction Tissue heart valves (first 3 months)	2.0–3.0
Bi-leaflet mechanical heart valve (aortic)	2.5–3.5
Mechanical prosthetic heart valve (high risk) Preventing recurrence of myocardial infarction Thrombosis in antiphospholipid antibody syndrome	3.0–4.5

Affects on warfarin dose of medicines and herbs

Warfarin interacts with many other medicines and herbs as well as some foods. Many interactions are unpredictable, so you will need to have your blood tested more often when you start or stop a new medicine or change its dose. We usually recommend tests twice weekly until the INR is stable for a week or two. Antibiotics are a common cause for over-anticoagulation.

Some of the important interactions of warfarin
Increased effect of warfarin (INR higher)	Decreased effect of warfarin (INR lower)	Potentiate bleeding risk because of antiplatelet effect	Potentiate bleeding risk by effects on gastric mucosa
Medications • Antibiotics (sulfonamides,cerythromycin and other macrolides, metronidazole) • Antifungals (itraconazole, fluconazole, ketoconazole) • Amiodarone • Selective serotonin reuptake inhibitors (especially fluvoxamine, fluoxetine) • Cimetidine • Propylthiouracil • Quinine and quinidine • COX-2 inhibitors (celecoxib, rofecoxib)	• Antiepileptics (carbamazepine, phenytoin, barbiturates) • Rifampicin, rifabutin • Cholestyramine	• Aspirin • Non-steroidal anti-inflammatory drugs (except COX-2 inhibitors) • Clopidogrel • Dipyridamole • Tirofiban	• Aspirin • Non-steroidal anti-inflammatory drugs
Herbal medicines • Dong quai • Garlic • Papaya • St John’s wort	• Ginseng

Fugh-Berman A. Herb-drug interactions. Lancet 2000;355:134-8

Affects on warfarin dose of alcohol

Alcohol in small to moderate amounts probably has little effect on warfarin metabolism. In heavy drinkers, however, the risk of bleeding is greatly increased.

Affects on warfarin dose of diet

Warfarin dose is affected by the amount of Vitamin K in you diet. Vitamin K is found in leafy green vegetables

Foods high in vitamin K include green tea, turnips, avocados, brussel sprouts, broccoli and green leafy vegetables (e.g. lettuce, cabbage).

There is no such thing as a ‘warfarin diet’ it takes a very large daily intake of ‘greens’ to influence the INR. A consistently sustained diet will minimise the risk of a fluctuating INR results

Consider testing twice weekly when diet changes, such as during illness, travel, fad diets, hospitalisation and following surgery.

Surgery and warfarin

The surgeon will have a view on the level of anticoagulation than can be tolerate for a particular procedure.

If a fully functioning clotting system is required for, say, brain surgery, stop warfarin 5 days before surgery.

If some level of anticoagulation can be tolerated, stop warfarin for 48 hours and the INR should fall below 2.0.

Warfarin can often be re-commenced in the early post-operative period; but it will take up to a week for the INR to re-enter the therapeutic range.

If the patient’s condition is such that anticoagulation must be maintained despite surgery, for example, mechanical heart valves—heparin or low molecular weight heparin (given by injection) can be used to cover the peri-operative period, after which warfarin be re-introduced.

Dental surgery

Most procedures can be carried out if the INR is <2.0.

Skin excisions

This is the most frequent surgery in older people in Australia. Some bleed profusely because of the combination of warfarin and fragile skin and blood vessels. Most surgeons do not require changes in warfarin therapy for skin excisions.

Testing your INR

Your blood can be tested at any time and fasting is not necessary for an accurate assessment of INR. You call your doctor the next day for advice on dosage and frequency of testing. Please try to arrange your tests so you can speak with your own doctor the next day. As not every doctor works every day ask you doctor what day will be best to test or you can check the hours your doctor works at reception and on our web page

here… http://www.lennoxmedical.com.au/staff/home.html

In general you will need test each day or second day until the dose becomes stable. The test frequency will then gradually reduce to weekly fortnightly or even monthly so long as the INR is stable. Testing frequency may however increase to each 3 days with any new medications.

In general if the dose of Warfarin is changing you should be seen at the surgery weekly if the dose is stable you should be seen monthly.

Decisions on dosage are best made by your doctor, based on your previous response to dosage changes, but below is an example of a dosage algorithm.

Dosage Adjustment Algorithm
		Current Daily Dose
		2.0	5.0	7.5	10.0	12.5
INR	Warfarin Dose Adjustment	Adjusted Daily Dose
1.0-2.0	Increase x 2 days	5.0	7.5	10.0	12.5	15.0
2.0-3.0	No change	2.0	5.0	7.5	10.0	12.5
3.0-6.0	Decrease x 2 days	1.25	2.5	5.0	7.5	10.0
Allow two days after dosage change for clotting factor equilibration. Repeat INR two days after increasing or decreasing warfarin dosage and use new guide to management. After increase or decrease or dose for two days, go to new higher (or lower) dosage level (e.g., if 5.0 qd, alternate 5.0/7.5; if alternate 2.5/5.0, increase to 5.0 qd.

Management of Oral Anticoagulant Therapy: Principles & Practice, prepared by the American Heart Association’s Post-Graduate Education Committee of the Council on Clinical Cardiology Data current as of October 1999.

Management of over-anticoagulation

If you are taking warfarin and have abnormal bleeding you should see your doctor.

Your doctors will check your INR and advise you on what to do if your INR is raised this advice will be based the indication for the warfarin, your risk of bleeding and whether it is safe to continue therapy at all. Some patients need to be admitted to hospital, while others just need to miss a dose of warfarin.

Guidelines for managing over-anticoagulation are based on recommendations from the Australasian Society of Thrombosis and Haemostasis. Vitamin K acts as an antidote to warfarin, however the life of vitamin K in the body is shorter than that of warfarin, so the INR may rebound 24-48 hours after giving vitamin K and the dose may need to be repeated. The intravenous preparation of vitamin K can be administered orally or subcutaneously with equal efficacy, and these routes are usually safer in patients who are not actively bleeding.

A protocol for managing over-anticoagulation
No bleeding
INR 4-5.9	Withhold warfarin and measure INR next day
INR 6-9	Vitamin K 1-2.5 mg subcutaneously or orally Recheck INR next day
INR >9	Hospitalise Vitamin K 5 mg IV or subcutaneously Fresh frozen plasma 2 Units. This may be given with a factor II, VII, IX concentrate Recheck INR after 6-8 hours and then daily for 3 days
Moderate or severe bleeding
INR>1.5	Vitamin K 5-10 mg intravenously Fresh frozen plasma 2 Units immediately Recheck INR after 6-8 hours and then daily for 3 days (may need further vitamin K if INR rises)
The intravenous preparation of vitamin K may be given orally or subcutaneously with safety and efficacy. Not all community pharmacies have the intravenous formulation of vitamin K it is always available at Ballina Hospital. (Avoid intramuscular injections of vitamin K to prevent local injection site bleeding which also reduces bioavailability.) Fresh frozen plasma and concentrates of clotting factors are blood products and may carry a small risk of viral contamination.

Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis. Med J Aust 2000;172:600-5.

Summary

Warfarin is an effective medication able to prevent strokes and clots but it can also cause life-threatening haemorrhages. If you are taking warfarin you should stick to the same brand and take it at the same time. You should have your INR measured regularly and always call for the result of your INR. Being on Wafarin means you will need to see your doctor frequently. You will need to be prepared for frequent tests when you start, stop or alter the dose of any other medications. You should report any abnormal bleeding and have your INR measured. A very high INR may lead to an admission to hospital to have the effects of warfarin controlled.

Warfarin self test

You can check your understanding of this information with the warfarin knowledge test, the link to this page is below and on the right.

Ref Peter Campbell (Aust Prescr 2001;24:86-9)