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o This guideline is intended to be used across Derbyshire and supports the new
level 4 anticoagulation management service being rolled out in Derbyshire County
PCT
o The patient should receive verbal and written information on anticoagulant therapy from
the start of treatment and an induction process followed to ensure they understand the
information
o Each patient should be issued with an oral anticoagulation therapy (OAT) pack containing
a anticoagulant record booklet (yellow booklet) which should be kept up to date.
8. Resources page 19
See Appendix 1 for detailed list of conditions, target INR and range and duration of treatment.
Predicted maintenance dosage of warfarin based on the sex of the patient and the INR after
2 weeks of 2mg/day.
MALE FEMALE
INR at Week 2 Maintenance Dose INR at Week 2 Maintenance Dose
1.0 6 mg/day 1.0 1.1 5 mg/day
1.1 1.2 5 mg/day 1.2 1.3 4 mg/day
1.3 1.5 4 mg/day 1.4 1.9 3 mg/day
1.6 2.1 3 mg/day 2.0 3.0 2 mg/day
2.2 3.0 2 mg/day > 3.0 1 mg/day
> 3.0 1 mg/day
6. Patients should re-attend after 1 week of the new dosage (day 22) for a further INR
measurement.
Changes in warfarin dosage should be kept to a minimum as there are natural fluctuations
in the INR which occur on a daily basis and because of external
factors.
4. Dosage Regimens
The dose required to achieve the therapeutic target is very variable between patients, but
usually lies between 1 and 10mg daily.
Dosage decisions should be supported using approved clinical decision support software
(CDSS) but clinical judgement must be applied in all cases to determine decisions.
The dose should be taken once a day at a fixed time, preferably 18.00 hours, or another
regular time if more convenient to aid better compliance. Patients are mostly seen during
the day and a late afternoon or evening dose does enable the managing practitioner to ask
the patient to miss a dose, when required. Management can be trickier if the patient has
already taken their anticoagulant.
The tablet strengths available are:
0.5mg (white), 1.0mg (brown), 3.0mg (blue) and 5.0mg (pink).
The use of 1mg strength tablets only is recommended unless patients are on high doses
greater than 5mg. Avoiding more than two different strengths is strongly recommended.
Use of 0.5mg is not recommended to avoid confusion.
The current INR and recommended dose should be recorded in the patients yellow
anticoagulant record book.
The recommended dose should always be specified in milligrams, i.e. Xmg, and not
number of tablets.
The NPSA recommends use of constant daily dosing and not alternate dosing. In practice,
fine tuning of dosage by using alternate day regimens of eg, 2 mg/3mg may need to be
used if INR fluctuates too much.
If a patient misses a dose of Warfarin they should be told not to take double the dose the
next day but continue with their normal dose. If the patient is very sensitive to changes or
at high risk if under dosed they should contact the service provider as soon as possible.
Other patients may be asked to arrange earlier monitoring if their appointment is not due
for more some time depending on stability of patient and clinical judgement of managing
practitioner.
5. Monitoring
The frequency of monitoring will vary but patients should have their INR checked at least
every 10 -12 weeks. Every patient must be seen at least once every 12 weeks. Less
stable and new patients will require more frequent tests
Recall dates will be suggested by the dosing support software; however, if the patients
clinical condition is changing, or there have been alterations in other medication, then the
INR should be checked more frequently and clinical judgement should override the CDSS.
7. Contraindications to Anticoagulation
This is seldom absolute and each patient must be individually evaluated.
Pregnancy: exposure of the embryo to warfarin during the 6th to 12th weeks of gestation
may be associated with the development of an embryopathy and throughout gestation
there is a continuing risk of foetal haemorrhage.
Patients who could potentially get pregnant must be warned of the risks and told to seek
an early pregnancy test if they suspect a risk.
Any patient taking Warfarin who becomes pregnant must stop Warfarin and be referred
urgently for hospital evaluation and management.
9. Cautions
There are certain conditions/problems where caution should be taken when monitoring
patients and where required advice from the Haematology department should be sought.
These include severe heart failure, liver failure, DVT /PE in the previous month and chronic
alcoholic.
Risk factors of bleeding should be considered. The following patient characteristics are
indicative of a high risk for bleeding: Age >70, Hypertension, Diabetes, Renal Failure,
Previous MI, Previous CVA, Previous GI Bleed, Patients with Liver Disease.
Patients with cancer are at a higher risk than non-cancer patients of recurrence of
thromboembolism despite adequate anticoagulation.
Patients with cancer who develop thromboembolism should be considered for treatment with
long term Low molecular weight heparin. It is preferable to use heparin in this circumstance,
and therapeutic anticoagulation with heparin therapy reduces the risk of recurrent events
compared with Warfarin therapy (BCSH guidelines on oral anticoagulation4)
1
Work competences for anticoagulant therapy: Available from the NPSA Website:
http://www.npsa.nhs.uk/
2,
Oates A, Jackson PR, Austin CA, Channer KS A new regimen for starting anticoagulation in
out-patients British Journal of Clinical Pharmacology 1998; 46: 157-171
3,
Channer Kevin S. Starting as an outpatient. BJGP 2002; 52 : 238-9
4
Guidelines on oral anticoagulation : third edition- 2005 update British Committee for Standards in
Haematology http://www.bcshguidelines.com/pdf/oralanticoagulation.pdf
Reference: Haemostasis & Thrombosis Taskforce of the British Committee for Standards in Haematology,
Guidelines on oral anticoagulation, British Journal of Haematology, 1998, 101, 174-187
Warfarin reduces the risk of people with atrial fibrillation (AF) having a stroke.
The risk of developing a blood clot and having a stroke varies, depending on various factors. The
level of risk is divided into three categories: high, medium and low risk.
High risk means that, without treatment, you have about a 6-12 in 100 chance (sometimes
higher) of having a stroke in the next year. People in the high risk group include those:
o who have already had a stroke or known blood clot, or
o are aged 75 years or older who also have one of the following 'risk factors': high blood
pressure, diabetes or a cardiovascular disease (such as angina, heart attack,
peripheral vascular disease), or
o who have a heart valve problem, or
o who have heart failure or poor heart function shown on a heart scan.
Moderate risk means that you have about a 3-5 in 100 chance of having a stroke in the
next year. People in the moderate risk group include those:
o aged 65 years or older (with no high risk factors), or
o who are of any age (up to age 75 when the risk is high) but who also have one of the
following 'risk factors': high blood pressure, diabetes or a cardiovascular disease (such
as angina, heart attack, peripheral vascular disease).
Low risk means that you have about a 1-2 in 100 chance or less of having a stroke in the
next year. People in the low risk group are all people with AF aged less than 65 and who
do not have any risk factors that put them in the high or moderate risk category.
Most people with AF who have a high or medium risk of having a stroke are advised to take
Warfarin. However, some people with a moderate risk may be treated with aspirin rather than
Warfarin (see below), particularly if the risks of taking Warfarin are higher than average. People
with a low risk of having a stroke are not usually advised to take Warfarin. This is because the
benefit does not usually outweigh the risk of serious bleeding problems with taking Warfarin. In
short, the decision to take Warfarin is a joint decision between you and your doctor. It involves
weighing up the risk of having a stroke against the small risk of a complication from taking
Warfarin.
Aspirin is another drug that helps to prevent blood clots forming. It is not as effective as Warfarin,
but is less likely to cause serious problems. It is usually advised if you only have a low risk of
stroke, or if you cannot take Warfarin or do not wish to take Warfarin.
If you cut yourself, or have any other bleeding, seek medical help as soon as possible if the
bleeding does not stop as quickly as you would expect. If you injure an arm or leg which is
bleeding, until you get medical help then ideally keep the affected part raised above the level of
your heart. If you vomit blood, get medical help immediately - ring for an ambulance.
Ideally, try to avoid activities that may cause abrasion, bruising, or cuts (for example,
contact sports). Even gardening, sewing, etc, can put you at risk of cuts. Do be careful and
wear protection such as proper gardening gloves when gardening.
Take extra care when brushing teeth or shaving to avoid cuts and bleeding gums.
Consider using a soft toothbrush and an electric razor.
Try to avoid insect bites. Use a repellent when you are in contact with insects.
Anticoagulation Europe
PO Box 405, Bromley, Kent, BR2 9WP
Tel: 020 8289 6875
Web: http://www.anticoagulationeurope.org/
A charity providing information and advice to people on oral anticoagulation treatment.
References
Atrial fibrillation, Clinical Knowledge Summaries (2007)
The management of atrial fibrillation, NICE Clinical Guideline (Jun 2006)
Mant J, Hobbs FD, Fletcher K, et al; Warfarin versus aspirin for stroke prevention in an
elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation
Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007 Aug
11;370(9586):493-503. [abstract]
Lip GY, Hart RG, Conway DS; Antithrombotic therapy for atrial fibrillation. BMJ. 2002 Nov
2;325(7371):1022-5.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS and PiP have
used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional
for diagnosis and treatment of medical conditions. For details see our conditions.
EMIS and PiP 2008 Updated: 17 Mar 2008 DocID: 4386 Version: 38
The following conditions may increase sensitivity to Warfarin and therefore warrant a
decrease in Warfarin dose:
Hepatic dysfunction and / or jaundice
Alcohol abuse particularly binge drinking
Congestive heart failure
Anorexia
Diarrhoea
Hyperthyroidism
Acute pyrexial episode
Changes in diet which reduce the intake of vitamin K *
Dietary components: Cranberry juice
Drugs (this list is not exhaustive):
Allopurinol
NSAIDs
Amiodarone Marked effect
Antibiotics Unpredictable / almost any antibiotic
Antifungals
Disulfiram
Tamoxifen
Statins
Thyroid hormones
Cimetidine
Antiplatelet agents Increased risk of bleeding
The following conditions may cause a decrease in sensitivity and therefore warrant an
increase in Warfarin dose:
Hypothyroidism
Changes in diet which increase the intake of vitamin K *
Dietary components: Dasheen
Herbal remedies: St Johns Wort, Gingko biloba
Drugs (this list is not exhaustive):
Anti-convulsants
Barbiturates
Rifampicin
Estrogens & progestogens
Sucralfate
Note: When these drugs are discontinued the dose must be reduced to avoid
dangerous over-anticoagulation.
Drugs marked * are liver enzyme inhibitors and increase the INR. They act very quickly (can be within 24
hours) and if the drug is withdrawn the effect disappears quickly depending on the drug half-life. The INR
should if possible be monitored within 72 hours of starting the interacting drug and on withdrawal.
Drugs marked $ are liver enzyme inducers and decrease the INR. They act more slowly (up to a week) with
peak effect at 2-3 weeks and can persist for up to 4 weeks after stopping depending on drug half-life. The
INR will need checking after
1 week of concurrent therapy.
Drugs with neither have other mechanisms, which affect the INR.
N.B. If a patient on warfarin were started on ANY other new medication a repeat INR after 1 week would be a
sensible
Drugs that increase the INR and risk of bleed
Gastrointestinal cimetidine*, omeprazole* and possibly other PPIs
Cardiovascular amiodarone* (liver enzyme inhibition is slow and may persist long
after withdrawal requiring weekly monitoring over 4 weeks),
fibrates, ezetimibe, propafenone*, propranolol,
statins no clinically relevant interaction will normally be seen
however it is prudent to check INR in the weeks after initiation and
at any dose change
CNS fluvoxamine*, SNRIs, SSRIs*, tramadol
Anti-infectives (anti- azole antifungals* (esp. miconazole including oral gel and
infectives in general may vaginal), co-trimoxazol*, macrolides* (can be serious but unpredictable),
cause raised INRs) metronidazole*, quinolones* (can be serious but unpredictable),
tetracyclines, influenza vaccine
Endocrine anabolic steroids (and danazol), high dose corticosteroids,
glucagon (high dose 50mg+ over 2 days), flutamide,
levothyroxine
NSAIDs Ibuprofen at lowest effective dose (+/-PPI) is probably safest if NSAID is required
N.B. All NSAIDs can increase the risk of bleeds and should be avoided if possible
Antiplatelets increased
bleed risk Aspirin, clopidogrel and dipyridamole
Miscellaneous Alcohol (acute), allopurinol*, benzbromarone*, colchicine, disulfiram, fluorouracil, interferon
paracetamol (prolonged use at high dose), sulfinpyrazone, tamoxifen, topical salicylates,
zafirlucast*
Herbal preparations/Food Carnitine, chamomile, cranberry juice*, curbicin, dong quai, fenugreek, fish oils, garlic, gingo
supplements biloba, glucosamine, grapefruit juice*, lycium*, mango, quilinggao
Based on original by Julian Holmes, Nottingham University Hospitals Trust, and further adapted by Derbyshire County
PCT
Updated by Aiste Baltramaityte and David Anderton Derby Hospitals NHS Foundation Trust.
The risk of bleeding associated with excess anticoagulation is a function of both the level of
the INR and the duration of time the patient is exposed to this excessive anticoagulation.
The following patient characteristics are indicative of a high risk for bleeding:
Age >70 Hypertension Diabetes Renal Failure
Previous MI Previous CVA Previous GI Bleed Liver disease
2. Guideline
The following recommendations (which take into account the recommendations of the British
Society for Haematology(1)) are based on the result of the INR and whether there is major or
minor bleeding; the recommendations apply to patients taking warfarin:
Major bleeding stop warfarin; give phytomenadione (vitamin K1) 510 mg by slow
intravenous injection; give dried prothrombin complex (factors II, VII, IX, and X BNF
section 2.11), 3050 units/kg or fresh frozen plasma 15 mL/kg (if dried prothrombin complex
not available). Seek specialist advice as required.
INR > 8.0, no bleeding stop warfarin, restart when INR < 5.0; if minor bleeding or there
are other risk factors for bleeding give phytomenadione 2.0 mg (using the intravenous
preparation orally a PDG is available in Derbyshire county); repeat dose of
phytomenadione if INR still too high after 24 hours.
If high risks and full reversal required quickly consider giving phytomenadione (vitamin K1)
500 micrograms by slow intravenous injection or 5 mg by mouth.
INR >6 major bleeding or minor bleed plus more then one risk factor give phytomenadione
2mg orally
INR 6.08.0, no bleeding or minor bleeding stop warfarin, restart when INR < 5.0
INR < 6.0 but more than 0.5 units above target valuereduce dose or stop warfarin, restart
when INR < 5.0
Unexpected bleeding at therapeutic levelsalways investigate possibility of underlying
cause e.g. unsuspected renal or gastro-intestinal tract pathology. Seek specialist advice.
IV Vitamin K administration leads to INR reversal within 4 6 hours, and is the fastest means
of INR reversal. Do not give IM injections. This can cause a muscle haematoma.
The oral route (Konakion paediatric 2mg per 0.2ml ampoule) being slower - Up to 24 hours.
This will readily reverse INRs within 16 to 24 hours to therapeutic doses.
Relevant references:
1. Guidelines on oral anticoagulation third edition
British Journal of Haematology 1998 101 374 - 387
2. Effective reversal of Warfarin induced excessive anticoagulation with Low Dose Vitamin K.
Thrombosis and Haemostasis 1992. 67. (1) 13 15.
3. Warfarin Reversal. J. Clin Pathol. 2004; 57 1132 1139
2. Explain Dosing
Colour of different strength tablets
On discharge, pharmacy supply tablets of 1mg strength only
When to take them i.e. at 6.00 p.m.(or another regular time if more convenient))
Length of treatment (if known)
8. Dietary advice
Speak to your Doctor, nurse or pharmacist at the clinic about changes in diet.
Eat a balanced diet.
Do NOT drink more than moderate amounts of alcohol (1 pint of ordinary strength beer per
day or the equivalent in pub measures of wine / spirits), as this can have an effect on blood
clotting.
10. Check patient understanding and repeat the main messages for the patient to take
away with them
Number of tablets
When to take them - i.e. 6.00 p.m. (or another regular time if more convenient)
What to do if they miss a dose
Length of treatment
Signs of bruising/bleeding to look for and what to do in case
They should check before receiving any treatment that the Dr/dentist/pharmacist knows
about their Warfarin
11. Ensure that the patient has a contact telephone number for the clinic managing
their blood tests in their booklet (if appropriate)
Plus the contact number of the lead clinician where appropriate
Plus the number for the A&E department where appropriate
Resources
Resources available from the NPSA Website: http://www.npsa.nhs.uk/
Or try http://www.npsa.nhs.uk/health/display?contentId=5754.
Patient safety alert 18: Actions that can make anticoagulant therapy safer
Anticoagulants are one of the classes of medicines most frequently identified as causing
preventable harms and admissions to hospitals. The NPSA has produced the following patient
safety alert and support materials to help manage the risks associated with anticoagulants and
reduce the risks of patients being harmed in the future.
All templates and exemplar documents provided as supporting materials for all patient safety
alerts are drafts intended for local adaptation. Organisations should ensure that they are adapted
locally and that they meet the requirements of specialist clinical areas and services and are
ratified prior to use.
The complete OAT pack or individual items such as the yellow record book can be obtained from
Derwent shared care services: Unit 7 Outrams Wharf, Alfreton Road, Little Eaton, DE21 5EL
NPSA report
Safety in doses: improving the use of medicines in the NHS (pdf 474KB)
Other Resources:
Available at: www.bcshguidelines.com
British Committee for Standards in Haematology. Guidelines for oral anticoagulants, Third Edition.
British Journal of Haematology. 1998; 101: 374-387.
If there are problems out of hours then the individual would be able to access advice either directly
from Dr Rod Collin, if he is on-call, or one of the other haematologists if they are on-call via the
hospital switchboard, which is what happens when GPs currently need help.
Other Hospitals:
Burton Hospital tel 01283 511511, anticoag ext 4040, fax 01283 593064.
Nottingham Hospitals QMC Campus..tel 0115 9249924, anticoag ext 68412, fax 0115 8754600,
tel direct line 0115 9194413.
Out of Hours
Derbyshire Health United (DHU) direct line for health professionals - 01246 550818