This presentation is designed to be delivered to people who work in a health care setting; such as nurses, carers and other nursing home staff. If you are an accredited pharmacist, you can use this presentation to help you deliver QUM services to a residential aged care facility. The first part of this presentation will address the features of warfarin, including indications for use, measuring INR, side effects and drug interactions. The second part of this presentation, will address patient education and important information that patient s taking warfarin should know. 1
Warfarin is the most widely used anticoagulant in the Western World. In the early 1950s, warfarin was approved for use as an anticoagulant, following its initial use as a pesticide. Warfarin works by inhibiting the Vitamin K dependent synthesis of clotting factors ll, Vll, lx and X in the liver. The degree of inhibition of these clotting factors is dependant upon the dose of warfarin administered i.e. the more warfarin administered, the greater the degree of anti-coagulation or bleeding. Anticoagulants, such as warfarin, do not have any effect on a established thrombus (or blood clot). However, once a thrombus has occurred, treatment with an anticoagulant can work to prevent further extension of this formed clot and prevent secondary complications. Murtagh J. Murtagh s General Practice. 5 th edn. Sydney: McGraw Hill; 2010. 2
Warfarin has a variety of clinical indications. These are summarised on this slide. Reference: 1. WA Medication Safety Group. Living with warfarin; Information for Patients. [Online]. 2007. [accessed 7 Dec 2011]. At: www.health.wa.gov.au/docreg/education/population/health_problems/hp8 948_warfarin_B.pdf 2. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310 3
Acute treatment with warfarin is required for: Pulmonary Embolism (PE): treatment continues generally for 4 to 6 months Deep Vein Thrombosis (DVT): as a result of surgery or immobilisation, treatment continues generally for 8 to 12 weeks 1. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310 4
Ongoing treatment with warfarin is required for the following conditions (after careful review of the patient s overall cardiovascular risk and risk of major bleeding with the treatment): Unprovoked or recurrent DVT Atrial fibrillation - Anticoagulant therapy with warfarin should be considered to prevent a first, or recurrent stroke in patients with atrial fibrillation Heart failure Myocardial infarction at risk of stroke Stroke prevention - warfarin reduces the relative risk of stroke in non-valvular AF. People with a previous stroke or transient ischaemic attack benefit from warfarin. 1. WA Medication Safety Group. Living with warfarin; Information for Patients. [Online]. 2007. [accessed 7 Dec 2011]. At: www.health.wa.gov.au/docreg/education/population/health_problems/hp8 948_warfarin_B.pdf 2. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310 5
Warfarin therapy is monitored by analysing the Prothrombin Time (PT). PT is the most commonly used test to monitor anticoagulant therapy. PT is usually expressed as the International Normalised Ratio (INR). The equation for the calculation of PT is displayed on this slide. The dose of warfarin must be individualised for each patient according to the patient s sensitivity to the medicine. The prescriber will adjust the dose based on a measure of the patient s prothrombin (PT) time. The PT time is based on interactions of the clotting factors (I, II, V, VII & X) which are synthesised by the liver. This will be discussed in more depth later in this presentation, when we address the aspect of INR testing with warfarin use. 6
The INR is the ratio of patient PT to control PT, multiplied by a correction factor called international sensitivity index (ISI- which is determined by the World Health Organisation and aims to standardise the test). It is a simple in vitro clotting assay which assesses the effect of warfarin on the coagulation system. A person not taking warfarin has a INR of about 1. The INR therapeutic range for all indications (except for those with heart valves) is between 2 and 3. Safety and efficacy of warfarin depends on maintaining the INR within the therapeutic range. The therapeutic range represents the levels at which therapy should be effective without an excessive risk of bleeding. The INR result reflects the warfarin dose administered 48-72 hours earlier. When the INR increases, there is an increase in the risk of bleeding and the warfarin dose needs to be reduced 1. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310 2. Murtagh J, Murtagh s General Practice. 5 th edn. Sydney: McGraw Hill, 2010. 7
Measure INR at baseline (before starting treatment) The typical starting dose for warfarin is 5-10mg daily. The dose is then adjusted according to the INR (reference tables exist for this process). Once the INR is within the required range (dependant upon the indication of use for warfarin), a maintenance dose is established (usually around day 5 of treatment). It is important to note that the INR reflects the warfarin dose taken 48 hours earlier. INR check if change in warfarin dose changes in the patient s condition addition or removal of other medication change in diet green leafy vegetables consumption change in the amount of alcohol consumed 1. Murtagh J. Murtagh s General Practice. 5 th edn. Sydney: McGraw Hill, 2010. 8
Warfarin is particularly prone to interactions with other drugs, herbal medicines and dietary factors. Many interactions are unpredictable, so the INR should be tested more frequently after starting a new medication and similarly when stopping a medication or changing the dose. INR measured about one week after a change in medication should reflect any interaction. These include: Age greater than 65 years; Elderly patients may exhibit an exaggerated response to warfarin, in part because they tend to store less vitamin K than younger people and therefore generally require a lower dose. Dose - The degree of inhibition of clotting factors, is dependant upon the dose of warfarin prescribed. Patient compliance - Problems with patient compliance can lead to irregular levels of warfarin in the blood stream. This can make dose adjustments difficult. Consider avoiding the use of warfarin if patient compliance is likely to be poor. The use of a dose administration aid (DAA) may be beneficial. Diet & vitamin K status - The amount of vitamin K in some foods can affect therapy with warfarin. Patient s should maintain a balanced diet and avoid any drastic changes in diet as this may affect vitamin K levels in the blood stream and can affect therapy with warfarin. Green, leafy vegetables contain high levels of vitamin K and patients should avoid eating large amounts of these. Lifestyle factors Avoid drinking large amounts of alcohol. Alcohol in small to moderate amounts probably has little effect on warfarin metabolism. In heavy drinkers, however, factors such as increased falls, alcohol-induced gastritis, poor diet and poor compliance potentiate the risk of bleeding. Other medications - Warfarin interacts with many medications when given at the same time. Refer to the tables over the next two slides for the main interactions. 9
There are many potential interactions between warfarin and other drugs. Importantly, some medications increase warfarin levels, whilst others decrease levels. Aspirin ( 2-4gm daily) is contraindicated while a patient is taking warfarin as this combination increases the risk of bleeding and GI upset. Low dose aspirin (100mg daily) can be given in selected patients at high risk of clotting. Close monitoring is required. In one study, recent antibiotic use was the second greatest risk factor (after age) for over-anticoagulation. Please note that this is not an exhaustive list. Patients should always check with their doctor or pharmacist before taking any other medicines with warfarin. Reference: 1. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310. 2. Murtagh J. Murtagh s General Practice. 5 th edn. Sydney: McGraw Hill, 2010. 3. Campbell P. Managing warfarin therapy in the community. Aust Prescriber. 2001;24:86-9. At: www.australianprescriber.com/magazine/24/4/86/9/ 10
Vitamin K reduces the anti-clotting effect of warfarin. Vitamin K is contained in some foods we eat. This is important to consider in situations when diet changes, such as during illness, travel, fad diets, hospitalisation and postoperatively. Foods high in vitamin K include green tea, turnips, avocados, brussel sprouts, broccoli and green leafy vegetables (e.g. lettuce, cabbage). Eat a consistent amount of these vitamin K-containing foods per week. Alcohol consumption in heavy drinkers ( above moderate intake) may cause fluctuations in INR and due to factors such as increased falls, alcohol-induced gastritis, poor diet and poor compliance potentiate the risk of bleeding. 1. WA Medication Safety Group. Living with warfarin; Information for Patients. [Online]. 2007. [accessed 7 Dec 2011]. At: www.health.wa.gov.au/docreg/education/population/health_problems/hp8 948_warfarin_B.pdf 11
If the INR value is elevated, this may be due to over-anticoagulation or high INR and increases the risk of haemorrhage. The first step in managing this problem is to identify the cause. Common causes include starting or stopping an interacting medication, deteriorating liver function, and patient error (such as taking the wrong dose or confusing different strength tablets). Many of these causes are preventable. The approach to a raised INR should be individualised, paying attention to the indication for the warfarin, the patient's 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. 1. Murtagh J. Murtagh s General Practice. 5 th edn. Sydney: McGraw Hill; 2010. 2. Campbell P. Managing warfarin therapy in the community. Aust Prescriber. 2001;24:86-9. 12
If the patient s INR is too low, this may be due to: a lack of patient compliance a fluctuating diet foods contained high levels of vitamin K are not kept constant an individual s personal circumstances 13
Bleeding is the most common side effect of warfarin use. It is greatest in the first three months of starting therapy. Signs that bleeding may be occurring are: Bleeding from the gums or nose Coughing up blood Red or dark-brown coloured urine Heavy bleeding form cuts or wounds that does not stop Easy bruising Severe headache Other side effects of warfarin are skin necrosis, purple discolouration of the toes, rash, nausea, vomiting and diarrhoea. 1. Blood and Electrolytes, Warfarin. In: Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd; 2011.p310. 2. INR record book. University of Tasmania. School of Pharmacy. [online]. 2010. [accessed 6 Dec 2011]. At: www.anticoagulation.com.au 3. Baker RI, Coughlin PB, Gallus AS, Harper PL, Salem HH, Wood EW. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Medical Journal of Australia. 2004; 181: 492 497. 14
The risk of haemorrhage must be considered against the potential clinical benefit of anticoagulation when considering the patient s: Localised physical conditions General physical condition Personal circumstances These will be discussed further on the following slides. Borosak M. Warfarin: balancing the benefits and harms. Aust Prescriber.2004;27:88-9. 15
Presenter s notes: For most patients, warfarin can be withheld 5 days before elective surgery; the INR usually falls to below 1.5 in this time, and surgery can be conducted safely. Borosak M. Warfarin: balancing the benefits and harms. Aust Prescriber. 2004;27:88-9. 16
Bleeding disorders- Warfarin is contraindicated in patient s with severe active bleeding or disease states with an increased risk of severe bleeding. (e.g. uncontrolled hypertension). Patient s who are at a high risk of bleeding, such as the elderly who may be prone to falls, should be monitored carefully if warfarin therapy is prescribed. Previous gastrointestinal bleeding Alcoholism- Alcohol can increase the anticoagulant effect of warfarin. There are some conditions in which warfarin should be used with caution in patients with: Cerebrovascular disease Heart failure Renal insufficiency Hepatic impairment Malignancy Borosak M. Warfarin: balancing the benefits and harms. Aust Prescriber. 2004;27:88-9. 17
In some patients due to their personal circumstances, warfarin use must be very carefully monitored. The decision to start warfarin depends on an assessment of each patient's balance between the harmful effects and the benefits of anticoagulation. Warfarin is contraindicated if the patient is unwilling or unable to comply with monitoring due to cognitive impairment, alcoholism, psychosis or problems with accessing services. Borosak M. Warfarin: balancing the benefits and harms. Aust Prescriber. 2004;27:88-9. 18
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