What should you monitor in a patient taking warfarin?

Warfarin is an oral anticoagulant used in the UK. Oral means it's taken by mouth. An anticoagulant is a medicine that stops blood clotting.

Clotting (thickening) is a complex process involving a number of substances called clotting factors.

Clotting factors are produced by the liver and help control bleeding. They work with cells that trigger the clotting process (platelets) to ensure blood clots effectively.

To produce some of the clotting factors, the liver needs a good supply of vitamin K.

Warfarin blocks one of the enzymes (proteins) that uses vitamin K to produce clotting factors. This disrupts the clotting process, making it take longer for the blood to clot.

When warfarin is prescribed

Anticoagulant medicines, such as warfarin, are often prescribed for people who've had a condition caused by a blood clot, such as:

Warfarin may also be prescribed for people at an increased risk of developing harmful blood clots, such as those with:

• a replacement or mechanical (prosthetic) heart valve
• an irregular heart rhythm, known as atrial fibrillation
• a blood clotting disorder, such as thrombophilia
• an increased risk of blood clots following surgery

Taking warfarin

It's very important that you take warfarin exactly as directed. Don't increase your prescribed dose unless the doctor in charge of your care advises you to.

Warfarin is taken once a day, usually in the evening. It's important to take your dose at the same time each day, before, during or after a meal.

The aim of warfarin therapy is to decrease the blood's tendency to clot, but not stop it clotting completely. This means the dose of warfarin you're taking must be carefully monitored and, if necessary, adjusted.

You'll have regular blood tests at your GP surgery or local anticoagulant clinic to make sure your dose is correct.

The international normalised ratio (INR) is a measure of how long it takes your blood to clot. 

The longer it takes your blood to clot, the higher your INR. Your INR will be used to determine the dose of warfarin you need to take.

Although there are now 3 new anticoagulants that don't require regular monitoring – rivaroxaban, apixaban and dabigatran – most people who need an anticoagulant will be prescribed warfarin.

When you start taking warfarin, you may be given a yellow booklet about anticoagulants, which explains your treatment.

How long you'll need to take warfarin for will depend on the condition for which it's been prescribed. Ask the healthcare professional responsible for your care if you're not sure.

Missed doses

If you usually take warfarin in the morning and forget to take it at your normal time, take it as soon as you remember and continue as normal.

However, if it's time to take your next dose, don't take a double dose to catch up, unless your GP has specifically advised you to.

If you forget to take your dose of warfarin in the evening but remember before midnight on the same day, take the missed dose.

If midnight has passed, leave that dose and take your normal dose the next day at the usual time.

Ask your GP or staff at your local anticoagulant clinic if you're not sure what to do about a missed dose of warfarin. You can also call NHS 24 111 service for advice.

Who shouldn't take warfarin

The following people shouldn't take warfarin:

Bleeding is the main side effect associated with warfarin, as it slows down the blood's normal clotting ability.

You're at greatest risk of bleeding in the first few weeks of starting treatment with warfarin and when you're unwell.

You should therefore seek medical attention if you:

• pass blood in your urine or faeces
• pass black faeces
• have severe bruising
• have long nosebleeds – lasting more than 10 minutes
• have bleeding gums
• cough up blood or have blood in your vomit
• experience unusual headaches
• have heavy or increased bleeding during your period, or any other bleeding from your vagina (in women)

Take extra care to avoid cutting yourself while taking anticoagulant medication because of the risk of excessive bleeding.

For example, you should:

• take care when shaving and brushing your teeth
• wear protective clothing when gardening, sewing or playing contact sports
• use insect repellent to avoid insect bites or stings

Seek urgent medical attention if you're taking warfarin and you:

• have a fall or accident
• experience a significant blow to your head
• are unable to stop any bleeding
• have signs of bleeding, such as bruising

Skin rashes and hair loss are also common side effects of warfarin.

Contact your GP or the healthcare specialist responsible for your care if you experience any persistent side effects while taking warfarin.

Interactions

Medicines

Warfarin can interact with many other medicines. The patient information leaflet that comes with a medicine should tell you if it's safe to take with warfarin.

Ask your GP or pharmacist if you're unsure.

When taking warfarin:

• don't take aspirin, or treatments containing aspirin, unless it's prescribed by a healthcare professional as it could cause bleeding 
• don't take ibuprofen unless it's prescribed by a healthcare professional
• you can take paracetamol, but don't take more than the recommended dose

Herbal medicines and supplements can also interact with warfarin. You should therefore avoid taking them without first checking with your GP, pharmacist, or staff at your local anticoagulant clinic.

Food and drink

Some food and drink can interfere with the effect of warfarin if consumed in large amounts, including foods that are rich in vitamin K.

Foods containing large amounts of vitamin K include:

• green leafy vegetables, such as broccoli and spinach
• vegetable oils
• cereal grains

Small amounts of vitamin K can also be found in meat and dairy foods.

When your first dose of warfarin is prescribed, it doesn't matter how much vitamin K you're eating because the dosage will be based on your current blood clotting levels.

However, if you make significant changes to your diet, such as increasing your vitamin K intake or cutting out foods that contain vitamin K, it could interfere with how warfarin works.

Consult the healthcare professional responsible for your care before making any significant changes to your diet while taking warfarin. They'll also be able to give you more information about foods to avoid or limit.

Alcohol

Getting drunk or binge drinking is dangerous while taking warfarin. It may increase the effect of the drug, increasing the risk of bleeding.

The latest guidelines on drinking alcohol state that regularly drinking more than 14 units of alcohol a week (for both men and women) risks damaging your health.

Fourteen units is equivalent to six pints of average-strength beer or 10 small glasses of low-strength wine.

Heavy drinkers or people with liver disease who are taking warfarin shouldn't drink alcohol.

Other useful information

Surgery and dental work

Because of the risk of bleeding, your dose of warfarin may need to be lowered or stopped a few days before having an operation or dental work.

Tell the surgeon or dentist that you're taking warfarin. You should also tell anyone else involved with your care, such as an anticoagulant nurse, if you need an operation so they can make arrangements.

Having vaccinations

You can have vaccinations while taking warfarin, but all injections must:

• be given under the skin
• not be given into the muscle as it may cause bruising 
• have firm pressure applied to the site for 10 minutes afterwards 

Playing sports

You can play sports while taking warfarin, but because of the risk of bleeding:

• contact sports that could lead to a head injury, such as football, rugby, cricket and hockey, are best avoided if played competitively
• martial arts and kickboxing must be avoided

You can continue to take part in non-contact sports, such as running, athletics, cycling and racquet sports. However, make sure you wear protective clothing, such as a cycle helmet.

Going on holiday

Tell your GP or anticoagulant nurse if you're going on holiday, in this country or abroad, and arrange to have your INR checked before you go.

If you're going to be away longer than a month, you may need to arrange to have your INR checked while you're away. Make sure you have enough warfarin tablets to last for the duration of your trip.

Body piercings

Body piercings aren't recommended while taking warfarin because of the increased risk of bleeding and risk of infection.

The goal of anticoagulant therapy with warfarin is to administer the lowest effective dose of the drug to maintain the target international normalized ratio (INR). Warfarin, a vitamin K antagonist, is an oral anticoagulant indicated for the prevention and treatment of venous thrombosis and its extension and the prevention and treatment of the thromboembolic complications associated with atrial fibrillation. Warfarin has also been used to prevent recurrent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction, but data supporting these indications are inconclusive at this time (1).

Warfarin inhibits the synthesis of clotting factors II, VII, IX, and X, as well as the naturally occurring endogenous anticoagulant proteins C and S (2). The anticoagulant and antithrombotic activity of warfarin depends on the clearance of functional clotting factors from the systemic circulation once the drug is administered (2, 3). The earliest changes in INR are typically seen 24 to 36 hours after administration of the dose. The antithrombotic effect of warfarin is not present until approximately the fifth day of therapy, which is dependent on the clearance of prothrombin (1, 2).

Initiation of warfarin therapy is challenging, since the pharmacodynamic response is delayed and difficult to predict. Because prothrombin has a half-life of around 50 hours, loading doses of warfarin are of limited value (4). In clinical practice, loading doses (e.g., 7.5 mg or more per day) of warfarin may increase the patient's risk of bleeding complications early in therapy by eliminating the production of functional factor VII (2, 5). Administration of loading doses may place a patient in a hypercoagulable state due to a severe depletion of protein C (2). The administration of a loading dose is a possible source of prolonged hospitalization secondary to dramatic rises in the INR value that may necessitate the administration of vitamin K (5). If a rapid anticoagulant effect is required, an initial dose of heparin or a low molecular-weight heparin should be used and overlapped with warfarin for approximately 4 to 5 days. Once the INR is therapeutic for at least 2 days, the supplemental anticoagulation treatment may be discontinued (1, 4, 5).

The safety and efficacy of warfarin therapy are dependent on maintaining the INR within the target range for the indication (Table ​1). When a patient is started on an oral anticoagulant, INR monitoring should be performed daily until the INR is within the therapeutic range for at least 2 consecutive days. Unexpected fluctuations in the INR in an otherwise stable patient could be due to a change in diet, poor compliance, undisclosed drug use, alcohol consumption, or self-medication (2). Lab error should also be considered for unexpected values.

Recommended therapeutic range for oral anticoagulant therapy*

One of the major risks of warfarin therapy is bleeding, which correlates well with INR values. The Fifth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy has published guidelines on the management of patients with high INR values with or without bleeding (Table ​2).

Management of supratherapeutic INR values*

Criteria for warfarin administration were developed that were supported by the medical literature and approved by the Drug Utilization Evaluation Subcommittee of the Pharmacy and Therapeutics Committee. A computer-generated report of all patients receiving warfarin was generated daily from July 24, 2000, to August 20, 2000. The information gathered was entered into Microsoft Access, and 50 patients were randomly selected to be included in the evaluation. A retrospective chart review was conducted for the patients identified through this randomized process. Descriptive and inferential statistics (chi-square, t test) were utilized for data analysis.

Overall, results identified 4 main variances related to warfarin therapy: 1) inappropriate administration of a warfarin loading dose, 2) inappropriate use of vitamin K, 3) inconsistent overlapping of heparin with warfarin, and 4) inconsistent provision of patient education.

Patients who are given a loading dose of warfarin often reach a supratherapeutic INR level that can place a patient at risk for bleeding and prolonged hospital stay. This complication has been attributed to excessive depression of factor VII and protein C (2, 5). The ACCP supports an “induction” dose (rather than a large loading dose) for initiation of therapy. This induction dose can range from 2 to 5 mg per day and is adjusted according to the patient's INR (1).

Inappropriate use of vitamin K can be improved by following the guidelines for dosing of vitamin K developed by the Fifth ACCP Consensus Conference on Antithrombotic Therapy (1). It is important to use vitamin K only when recommended, because inappropriate administration of vitamin K is associated with warfarin resistance. When such resistance develops, it is difficult to achieve a therapeutic INR in a timely manner, which may result in an increased risk of clotting events.

Another area of improvement relates to the practice of overlapping heparin with warfarin therapy. Heparin displays an anticoagulant effect within 1 day, while the anticoagulant effects of warfarin are not evident until the third day of therapy. If rapid anticoagulant effects are needed, heparin should be initiated first, and warfarin should be started within a day or two. The 2 drugs should be given concurrently until the INR value is within the therapeutic range (1–3).

Lastly, since warfarin has a narrow therapeutic window and has been associated with many drug-drug and drug-food interactions, patient counseling is crucial. The evaluation revealed this as an area for improvement because opportunities for patient education were not always optimized.

Initiation and management of warfarin therapy is often difficult. Guidelines have been developed to assist the clinician in determining target ranges for therapeutic success. In addition, strategies for rapid anticoagulation and management of supratherapeutic INR values are also described in the literature. Daily practice using these guidelines should make management of patients easier when warfarin therapy is required.

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