Safer Anticoagulation Therapy

1. Safer Anticoagulation Therapy

2. Why? NPSA (National Patient Safety Agency): Actions that make anticoagulant safer – action. Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital.1 500 000 patients in the UK are currently prescribed oral anticoagulants.2 Risk assessment of anticoagulant treatment. (2006). Available at: www.npsa.nhs.uk/health/alerts Baglin T.P et all, BJH: Recommendations from the British Committee for Standards in Haematology and National Safety Agency, 2006; 136: 26-29

3. Learning objectives Understand working mechanism and use of warfarin Know common side effects and risks for patients on warfarin Understand the importance of INR measuring and monitoring Understand and re-enforce the importance of anticoagulation booklet

4. Target audience All Nursing Staff Doctors & RMO’s Pharmacy Staff Allied Healthcare Professionals (with an interest in anti-coagulation)

5. Content of course Introduction to anticoagulation and therapy options Warfarin Mechanism of action Pharmacokinetics Signs and symptoms of bleeding Monitoring of warfarin therapy Factors influencing response to warfarin Initiating, maintaining and stopping of warfarin therapy Patients counselling Management of over-anticoagulation Case study Heparin Low molecular weight heparin Test your knowledge

6. Introduction to anticoagulation The aim of anticoagulant therapy is to prevent thromboembolic events Thrombus formation may result in eg. Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) Cerebrovascular accident / stroke Factors influencing the formation of thrombi: Rate of blood flow (atrial fibrillation) Disruption of normal blood flow (heart valve replacement) Coagulation disorders (thrombophilia)

7. Anticoagulation therapy options Oral: Warfarin – the most frequently prescribed in the UK Acenocoumarol Phenindione Intravenous: Heparin Subcutaneous: Low molecular weight heparin (eg. Enoxaparin, Dalteparin,Tinzaparin)

8. Mechanism of action of warfarin Warfarin interferes with the hepatic synthesis of vitamin K- dependent clotting factors and reduces the concentration of factor II (prothrombin), VII, IX and X It does nothave any effect on clotting factors already in circulation Warfarin will not dissolve existing clots

9. Pharmacokinetic of warfarin The dose of warfarin should be titrated to obtain desired response for an individual (target INR) and that may take several days It takes 8 days to reach constanttherapeutic levels The duration of action is 2-5 days

10. Balancing risks and benefits Benefits of Warfarin Risks of Warfarin Lower risk of stroke & clots Increased risk of bleeding

11. Signs and symptoms of bleeding Prolonged nosebleeds (more than 10 minutes) Blood in vomit Blood in sputum Unusual or severe headaches Blood in urine Black stools Severe or spontaneous bruising Heavy or increased bleeding during period or any vaginal bleeding

12. Monitoring warfarin therapy INR (International Normalised Ratio) is a standardised index used for monitoring warfarin therapy and it represents the time taken for the sample to clot The BCSH (British Committee for Standards in Haematology) guidelines recommend “target INR’s” for different indications An “INR range” is0.5 INR units on both sides of the target INR, for example, the INR range for a target INR of 2.5 is 2.0 – 3.0

13. Factors influencing response to warfarin Drug interactions (including herbal remedies) Disease states Pregnancy Diet Alcohol Concordance

14. Drug interactions A pharmacokinetic interaction will alter the plasma concentration of warfarin and result in a change in the INR A phamacodynamic effect is one that ↑ the risk of bleeding without altering the plasma concentration of warfarin These may lead to a loss of anticoagulation (↑ risk of thrombosis) or cause over-anticoagulation (risk of haemorrhage) » monitoring during introduction, discontinuation or dose adjustment of any interacting medication

15. Drug interactions A lot of medication can have an influence on the INR and interact with warfarin Information on drug interactions can also be found in the BNF The ward Pharmacist, as well as the Community Pharmacist can provide further information on drug interactions (inc. herbal products and OTC’s) e.g. NSAID’s (diclofenac, aspirin), some antibiotics (erythromycin, ciprofloxacin), SSRI’s (citalopram), amiodarone, cranberry juice

16. Disease states Many disease states may alter the effects of warfarin, including: Hypothyroidism - ↑dose of warfarin required Hyperthyroidism & Fever - ↓ dose of warfarin required Liver disease– warfarin is contraindicated in severe liver disease Congestive heart failure- ↑ risk of bleeding, due to secondary impaired liver function

17. Many diseasesassociated with stroke and thromboembolism become more common with increasing age Generally, elderly people have an increased sensitivity to warfarin and require lower mean daily dose Polypharmacy increases the chance of drug interactions Decline in cognitive function – challenge in safe and effective management Age

18. Pregnancy Warfarin is teratogenic and should not be given in the 1st trimester of pregnancy Warfarin crosses the placenta and may cause placental or foetal haemorrhage (1st& 3rd trimester) Alternativetreatment in pregnancy is LMWH or unfractionated heparin Women can breast-feed while on warfarin

19. Diet A well balanced, consistent diet, is recommended “Crash” diets or “binge” eating should be avoided whilst on warfarin Change in vitamin K - rich food diet can influence anticoagulant effect of warfarin

20. Alcohol Alcohol can increase or decrease INR Binge drinking should be avoided, as this can increase the INR Alcohol consumption should not exceed national recommendations (female 2 units, male 3 units per day) A chronic alcoholic may show diminished effect from warfarin and this can decrease INR

21. Concordance Poor concordance may be reason for unexpected variations in anticoagulant control Therefore patients and carers should receive adequate verbal and written information about their warfarin treatment Information should be provided before the therapy initiation, reinforced upon discharge from hospital, at the first anticoagulation clinic appointment, and whenever necessary throughoutthe course of treatment

22. Warfarin contra indications Absolute: Pregnancy (1st and 3rd trimester) Active peptic ulcer Severe hypertension (BP200/120 mm/Hg) Caution required: Renal impairment Severe liver disease Recent surgery

23. Making up a correct dose The warfarin tablets come as different strengths, the different strengths have different colours! Making up a dose needs to be explained to the patient e.g. 6mg can be given as 2 x 3mg or as 1 x 5mg and 1 x 1mg NB: 0.5mg tablets are not commonly used within HCA

24. Initiating treatment 1 Beforeinitiating - assessment of the patient’s status is necessary, including: Indication of treatment Duration of the treatment Appropriate INR target range Full clotting screen Liver Function Tests (LFTs) Warfarin takes several days to have therapeutic effect For urgent anticoagulation (e.g.PE, DVT) loading doses are required to achieve the target INR faster

25. Initiating treatment 2 Loading doses for rapid anticoagulation – heparin or LMWH & warfarin are usually initiated together, with heparin being withdrawn once a stable INR is reached BCSH guidelines recommend consequent heparin therapy for at least 5 days and that should not be discontinued until INR reaches therapeutic range for 2 consecutive days INRlevel is usually tested daily until the aimed range is achieved and the patient is stable

26. Initiating treatment 3 For non-urgent cases slow loading regime is safer Therapeutic anticoagulation can be reached within 3-4 weeks This regime is more often used in the community and is often unsuitable in hospital

27. Maintaining treatment 1 Once the patient is stabilised, daily INR measurements can be reduced(according to concordance and control) to once weekly and then every 1-2 months Intervals between measurements should not exceed 3 months as per BCSH guidelines More frequent monitoring is required in case of any changes to medication, diet or disease state

28. Maintaining treatment 2 Changes to maintenance dose should generally be made in small increments Dose adjustments should be made by looking at weekly dose not daily dose Before adjusting the dose of warfarin this should be reviewed: Previous dose of warfarin Earlier INR results Any changes to the patient’s clinical condition Any changes to medication or lifestyle Alcohol consumption

29. Stopping treatment Warfarin can be stopped abruptly when the prescriber decides that it is not necessary for the patient to continue with the treatment There is no evidence to suggest that abrupt discontinuation of warfarin leads to increase risk or harm

30. Patients education 1 Patients education is one of the key factors in minimising adverse effects and keeping patients on warfarin well Information should be provided to the patient before the therapy initiation, reinforced upon discharge from hospital, at the first anticoagulation clinic appointment, and whenever necessary throughout the course of treatment

31. Patients education 2 Patients, relatives and carers should be educated on the advice in the “yellow anticoagulation booklet” on discharge The new booklet is larger and has three sections: The anticoagulation alert card(credit card-size alert to be carried at all times) General information about safe use of anticoagulants(to be used for reference when needed and provides concise information about the practical issues and key advice for patient) Blood test results and dosage information(section providing space for written record of the INR test results, dosage and next clinic appointment information)

32. Key points of patients counseling 1 Use of the “yellow booklet” - go through the information with the patient Indication of therapy- why and how it works Duration of therapy Importance of regular blood tests The dose should be taken at the same time every day (usually at 6pm, not in the morning) Explain the different strengths and colours of warfarin tablets and how to make up required dose

33. Key points of patients counseling 2 Patients must inform their doctor if they have missed dose or have taken too much warfarin Balanced and stable diet Alcoholconsumption – no binge drinking Druginteractions – speak to the pharmacist if necessary Plan of pregnancy – notify doctor Patients should notify healthcare professionals e.g. dentist about taking warfarin – possible need of stopping warfarin before surgery

34. Inform the patient of signs of bleeding: Bruising Bleeding gums Nosebleed Prolonged bleeding from cuts Blood in stools and urine Advice patients of extra care when brushing teeth or shaving, avoid activities which could cause abrasion, bruising or cuts Key points of patients counseling 3

35. Warfarin Counseling Tool Warfarin Counseling tool (refer to the handout) It is good practice to use this tool, as part of the discharge counseling Once completed and signed, it is filed under the patients notes

36. Management of over-anticoagulation Major bleeding Stop warfarin, give phytomenadione ( vitamin K1) 5-10 mg by slow IV injection; give prothrombin complex concentrate 30-50 units/kg or fresh frozen plasma 15ml/kg INR > 8, no bleeding or minor bleeding Stop warfarin, restart when INR < 5; if there are other risk factors for bleeding then give vitamin K1 0.5 mg by slow IV or 5mg orally; repeat dose of vitamin K1 if INR still to high after 24 hours INR 6 - 8 no bleeding or minor bleeding Stop warfarin, restart when INR < 5 INR < 6 but more than 0.5 value above target value Reducedose or stop warfarin, restart whenINR < 5

37. Wilma is 76-year old woman admitted to the hospital with atrial fibrillation. She suddenly presents with large haematoma on her side which is weeping slightly. Her last INR test (4 days ago) was within range. She was commenced on erythromycin 6 days ago.It has been noticed that she was having cranberry juice for breakfast whilst in hospital. What is Wilma’s INR target range and duration of therapy? Another INR test has been done and the result was 6. What was the cause of the rising INR? How would you manage this situation? Why was the INR result 4 days ago within range? What is the recommendation when initiating therapy interacting with warfarin? Antibiotic treatment was stopped and patient stabilised. The patient was ready to be discharged. How would you counsel the patient? Case study

38. Heparin-unfractionated Inactivates clotting factors Is administered parentally Rapidlyacting: Heparin has short half life (20-150 minutes) Peak levels after 4-5 hours Effect last about 12 hours depending on dose Efficacy is measured by Activated Partial Thromboplastin Time (APTT); ratio above 2.5 is associated with risk of bleeding and below 2.0with risk of thromboembolism(refer to local guidelines)

39. Heparin dose Heparin is usually initiated with bolus dose of 5000 units followed by continuous infusion of 1000units/hour Please refer to your local guidelines for correct dosing,if your facility does not have available guidelines refer to your pharmacist for further information Doses are then adjusted according to APTT (measured at least once daily) APTT are measured 6 hours after any dose change

40. Heparin contraindications Haemophilia and other haemorrhagic disorders Thrombocytopenia Recent cerebral haemorrhage Severe liver disease Severe hypertension Acute bacterial endocarditis Acute peptic ulcer Acute tuberculosis

41. Adverse effect of heparin Thrombocytopenia (usually appears between 5 & 21 of treatment)–monitor platelet levels Hyperkalaemia–monitor potassium levels Osteoporosis Alopecia Bleeding–stopping the infusion should be sufficient as heparin has a short half life

42. Low Molecular Weight Heparin (LMWH) LMWH inhibits factor Xa and has a long half life Generally administered subcutaneously once daily and therapeutic level monitoring is not required (see BNF for doses and frequency) Low doses are used for prophylaxis of DVT and thromboembolism Caution is required in renally impaired patients due to accumulation of the drug

43. THIS IS Clinical Induction Question Time ?