WARFARIN & OTHER ORAL ANTICOAGULANTS GUIDELINES AND PROCEDURES

Transcription

1 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet WARFARIN & OTHER ORAL ANTICOAGULANTS GUIDELINES AND PROCEDURES This guidance does not override the individual responsibility of health professionals to make appropriate decision according to the circumstances of the individual patient in consultation with the patient and /or carer. Health care professionals must be prepared to justify any deviation from this guidance. Introduction Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital. Managing the risks associated with anticoagulants can reduce the chance of patients being harmed. This Trust Guideline is based on British Committee for Standards in Haematology (BCSH) and National Patient Safety Agency (NPSA) guidance This guideline is for use by the following staff groups : All staff caring for or managing patients on anticoagulant therapy must have the necessary Trust adapted NPSA work competences/procedures included in this document (See Part 2.) Dr Salim Shafeek Dr. Crowther Lead Clinician Consultant Haematologist Consultant Haematologist Approved by Medicines Safety Committee on 4 th September 2014 This Guideline not to be used after: 4 th September 2016 Key amendments to this guideline Date Amendment By: April 2012 Expiry extended to July 2012 whilst under review M Crowther June 2012 Major changes to the Guideline. Warfarin indications rewritten M Crowther based on latest BCSH guidelines, warfarin management and reversal re-written based on new oral anticoagulant prescription charts and section on rivaroxaban and dabigatran included for the first time. November Addition of more prescribing information for dabigatran and M Crowther 2012 rivaroxaban and prescriber and patient information sheets December 2012 Bridging therapy tables re-written to be more clear M Crowther E Maughan Feb 2014 Addition of apixaban and some minor changes M Crowther 20 th October 2014 Amendment made to the table in Indications for VKA and target INR section. Changed > to < in Indication column on table. M Crowther WAHT-HAE-002 Page 1 of 43 Version 5.1

2 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Contents List Introduction 4 Staff competencies 4 Part One Clinical Guidance 5 Vitamin K antagonists 5 Indications for VKA and target INR 5 Contra-indications for VKA 6 Dosing of VKA 7 Discharge arrangements 9 Information for Patients 9 Reversal/stopping of VKA s including management of bleeding and a high INR 9 Perioperative management of VKA s 10 The new oral anticoagulants 13 Direct thrombin inhibitors - Dabigatran 13 Management of patients on Dabigatran undergoing surgery 14 Management of bleeding on Dabigatran 14 Oral factor Xa Inhibitors Rivaroxaban and apixaban 15 Bleeding 16 Anticoagulant Clinic Process map Hospital dosed patients 17 Anticoagulant Clinic Process map GP dosed patients 19 References 20 Audit 20 Appendix 1 Thrombophilia screening 21 Causes of Thrombophilia 21 Appendix 2 Information sheets on the new Anticoagulants 22 Appendix 2.1 Management of patients taking Dabigatran, Rivaroxaban and 23 Apixaban who have bleeding or require surgery Appendix 2.2 Low molecular weight Heparin and Warfarin or Rivaroxaban for 27 the treatment of deep vein thrombosis or pulmonary embolism Appendix 2.3 Patient information on Anticoagulants (blood thinning drugs) for 30 the treatment of deep vein thrombosis Appendix 2.4 Flowchart to decide who would be suitable for Rivaroxaban 31 Part Two Inpatient Anticoagulation with Oral Anticoagulants in WAHT 32 responsibilities of each profession Procedures/Competencies 35 Initiating Oral Anticoagulant therapy Authorised Prescribers 35 Maintaining Oral Anticoagulant therapy 37 Dispensing Oral Anticoagulants 38 Administering (and discharging patients on) Oral Anticoagulants 39 Contribution list 41 Supporting Documents Supporting Document 1 Equality Impact Assessment Tool 42 Supporting Document 2 Financial Impact Assessment 43 WAHT-HAE-002 Page 2 of 43 Version 5.1

3 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Introduction Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm and admission to hospital. Managing the risks associated with anticoagulants can reduce the chance of patients being harmed. This Trust Guideline is based on British Committee for Standards in Haematology (BCSH) and National Patient Safety Agency (NPSA) guidance. The NPSA recommends that NHS and independent sector organisations in England and Wales take the following steps: 1. Ensure all staff caring for patients on anticoagulant therapy have the necessary work competencies. Any gaps in competence must be addressed through training to ensure that all staff may undertake their duties safely 2. Review and, where necessary, update written procedures and clinical protocols for anticoagulant services to ensure they reflect safe practice, and that staff are trained in these procedures. 3. Audit anticoagulant services using BCSH/NPSA safety indicators as part of the annual medicines management audit programme. The audit results should inform local actions to improve the safe use of anticoagulants, and should be communicated to clinical governance, and Drugs and Therapeutics committees (or equivalent). This information should be used by commissioners and external organisations as part of the commissioning and performance management process. 4. Ensure that patients who are prescribed anticoagulants receive appropriate verbal and written information at the start of therapy, at hospital discharge, on the first anticoagulant clinic appointment, and where necessary throughout the course of their treatment. The BSH and the NPSA have updated the patient-held information (yellow) booklet. 5. Promote safe practice amongst prescribers and pharmacists to ensure that INR s are not only monitored regularly but also that levels are safe before issuing or dispensing repeat prescriptions for oral anticoagulants. For more detail on each of these please see the full Patient Safety Alert at: Staff competencies All staff caring for or managing patients on anticoagulant therapy must have the necessary Trust adapted NPSA work competences/procedures included in this document (See Part 2.) Any gaps in competence must be addressed through training to ensure that all staff may undertake their duties safely. E-learning modules are available at WAHT-HAE-002 Page 3 of 43 Version 5.1

4 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Part One Clinical Guideline The following oral anticoagulants are licensed for use in the United Kingdom: Vitamin K antagonists Warfarin, Acenocoumarol and Phenindione Direct thrombin inhibitors Dabigatran Direct inhibitor of factor Xa Rivaroxaban and Apixaban Vitamin K antagonists Coumarins: Warfarin (Marevan) is the most commonly used oral anticoagulant in the UK. It is available as 0.5mg (white) 1mg (beige), 3mg (blue) and 5mg (pink) tablets (Note that 5mg tablets should not be used in Worcestershire to avoid confusion with 0.5mg tablets). Acenocoumarol (Sinthrome ) is occasionally used in patients who cannot tolerate warfarin. It is available in 1mg tablets. Inanediones: Phenindione (Dindevan) is occasionally used in patients who cannot tolerate warfarin. It is available as 10mg, 25mg and 50mg tablets. Vitamin K antagoinists (VKA) are competitive antagonists of vitamin K, which is required for the synthesis of clotting factors II, VII, IX and X. They have a slow onset of action (48-72 hours) and long half life. Because of variable pharmacokinetics (due to vitamin K in the diet, genetic polymorphisms and their metabolism by Cytochrome P450) VKAs have variable dosing between patients. The dose may change over time given changes to diet, activity and concurrent medications. These factors require the monitoring of their effect and dose adjustment if necessary. Their effect is monitored using the International Normalised Ratio (INR). Because of their long half-lives and slow action on the coagulation process all of the VKAs require once-daily dosage. The daily dose should be given, if possible, at a fixed time, e.g hours, to facilitate monitoring and any associated dosage change as necessary before the next dose is due. The INR is derived from the prothrombin time and an international standard which should provide consistent INR results on the same patient between laboratories. Laboratory INR testing requires a venous blood sample, collected into a sodium citrate containing tube (light blue top) in the correct proportion of blood to anticoagulant. Over or under-filled sample tubes may give erroneous results. Samples for INR testing can safely be stored overnight at room temperature without significant change in the INR result. Near-patient testing of the INR is possible using capillary whole blood samples e.g. with the CoaguChek machine, but this should only be undertaken in the presence of a comprehensive quality assurance programme. Indications for VKA and target INR It is now required practice to define a target INR for the patient and to make dose adjustments based on deviation from the target. This is also the principle used by many of the computerised decision support systems (CDSS) for warfarin control e.g. DAWN, INRstar. It is usual to aim to maintain a patient s INR within +/- 0.5 units of the target INR. The following is taken from the BCSH Guidelines on Warfarin which discusses indications in more detail. WAHT-HAE-002 Page 4 of 43 Version 5.1

5 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Indication Target INR Duration 1 st episode of DVT/PE 2.5 Line associated thrombosis 6 weeks Calf vein DVT 3 months Provoked DVT (assuming provoking factor removed) 3 months Unprovoked DVT/PE six months with consideration of long-term if additional factors e.g. antiphospholipid syndrome 2 nd episode of DVT/PE 2.5 (3.5 if recurrence when adequately anticoagulated) Lifelong for unprovoked events, as above for recurrent provoked events Atrial fibrillation with additional risk factor 2.5 Lifelong Cardioversion (warfarin may not be required if onset of AF is <48hours) 2.5 (3.0 may be considered to reduce chances of a cancelled procedure due to a low INR) 3 weeks prior and 4 weeks after Mitral stenosis/regurgitation with atrial fibrillation, enlarged left atrium or atrial thrombus 2.5 Lifelong Mechanical or bioprosthetic valve Dependent on valve type consult cardiothoracic centre Dependent on valve type consult cardiothoracic centre Arterial embolism 2.5 Lifelong Dilated cardiomyopathy 2.5 Lifelong Contra-indications for VKA Contra-indications are seldom absolute but should be considered in all patients: Stroke Haemorrhagic stroke is a contraindication to oral anticoagulant therapy. In patients with ischaemic stroke anticoagulation therapy increases the risk of secondary haemorrhage into the infarcted area of brain. Patients with atrial fibrillation who have had an ischaemic stroke longterm oral anticoagulation is beneficial but should be deferred 14 days after the ischaemic stroke, depending on the size of the infarct and blood pressure. In patients who have sustained a large embolic stroke or have hypertension that needs to be controlled anticoagulation should not be initiated within 14 days. Initial heparinisation should be avoided. Additional Contraindications include: Severe or uncontrolled hypertension. Bacterial endocarditis WAHT-HAE-002 Page 5 of 43 Version 5.1

6 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Uncooperative patients or those with mental impairment. Alcoholism. Recent trauma or surgery to the CNS or eye. Uncompensated cirrhosis of the liver. Peptic ulcer Pregnancy Pre-existing haemostatic defect - Since many cardiological indications for anticoagulation are prophylactic, always consider the possibility of a pre-existing bleeding tendency before starting oral anticoagulants. A coagulation screen, including INR and APTT should be checked. The platelet count should also be checked. Cautions with VKA Recent surgery Elderly patients (greater risk of major bleeding ) Substance misuse Cancer Hepatic or renal impairment Breastfeeding Intramuscular and Intra-articular injections - Avoid IM injections in anticoagulated patients if possible. If it is necessary to give an IM injection, apply prolonged pressure to the injection site to minimize bruising. Warn patients of the possibility of haematoma formation. Intra-articular injections are contra-indicated in anticoagulated patients. Dosing of VKA This section will primarily deal with the dosing of warfarin. There is less information surrounding the dosing of acenocoumarol and phenindione, but their principle is the same as warfarin. Acenocoumarol doses tend to be lower than warfarin (maintenance 1-8mg/day compared with 3-9mg for warfarin) while phenindione has higher doses (maintenance mg/day). It is best to take a more cautious approach to dosing these unfamiliar drugs. Prescription charts All VKAs should be prescribed on the designated WHAT Adult Oral Anticoagulant Chart & Discharge Referral WR1779 Version 5, called oral anticoagulant chart in this document. All the required information should be entered for each patient. The chart is designed for warfarin prescribing, if acenocoumarol or phenindione is used then this should be written clearly on the chart. It should also be recorded on the patient s main drug chart that they are on a VKA and that the oral anticoagulant chart is also in use. Initiation of Warfarin Before initiation of warfarin the patient should be fully counseled over the risks and benefits of warfarin, family members/carers may also be involved. This discussion along with the indication, target INR and intended duration should be documented in the notes and on the anticoagulant chart. Warfarin requires a loading dose which is higher than the normal maintenance dose, it is during the initiation of warfarin that there is the highest risk of a high INR and therefore bleeding complications. There are three initiation regimens: WAHT-HAE-002 Page 6 of 43 Version 5.1

7 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet 1. Standard dose induction, this aims to achieve a therapeutic INR within 3-4 days and is used to reduce the time that the patient is on alternative anticoagulants, e.g. heparin, following the diagnosis of a thrombosis. 2. Low dose induction, this is for patients that require a therapeutic INR within 3-4 days but are at a higher risk of bleeding. 3. Very low dose induction, this is for patients usually in the community who require warfarin for AF without evidence of thrombosis. The patient receives 1mg for a week then has an INR check and the dose is increased by 1mg/week until the INR is therapeutic. The advantage to this regimen is the lower frequency of INR checks and the low probability of a high INR. The first two regimens tend to be used in hospital. When commencing a patient on warfarin it is important to determine if the patient requires a standard or low dose induction. Risk factors requiring a low dose regimen are listed at the front of the oral anticoagulant chart. If a patient has one of these factors then the low dose regimen should be used. The person prescribing the warfarin must tick if a risk factor is present and sign that either the low or standard induction regimen is to be used. Once it is determined which regimen is to be used then that days INR and warfarin dose must be entered in the chart, this is then signed for. The nurse administering the warfarin should only administer the warfarin if the chart is properly completed. For the first four days there must be a daily INR performed and recorded on the chart. Dosing is dependent on the INR and suggested doses are recorded on the chart. Warfarin should not be administered without a daily INR. It might be prudent to start warfarin at the start of a week, maintaining them on low molecular weight heparin (LMWH) if there is a thrombosis, if the patient is going home to prevent problems with INR checks over the weekend. Alternative anticoagulation given when there is a thrombosis, usually LMWH, needs to continue for at least five days and until the INR is therapeutic for 2 days, this is due to the initial procoagulant activity of warfarin. Consideration should be given to the re-introduction of alternative anticoagulation if the INR falls below the desired therapeutic range in the first 4 weeks of treatment for a thrombosis or if there is a prolonged period (>3 days) when the INR is sub therapeutic. Warfarin maintenance The important factor when managing long-term warfarin is to make only minor changes to the dose to avoid large variations in the INR, suggestions are: Not to worry about one off readings slightly outside the normal range (e.g 1.8 or 3.6) Trends are more important than one off readings Small daily doses of warfarin require small adjustments, adjust total weekly dose rather than daily dose. When a patient is admitted on warfarin page 2 of the oral anticoagulant chart needs to be completed. Information on pre-admission dose, target INR, indication and intended duration needs recording on the chart and in the medical notes. An INR must be recorded on admission and no warfarin should be prescribed or administered without an INR. For each day the prescriber must write the dose and the INR, where the INR is not required an X must be put in the box and this signed for. The nurse administering the warfarin must sign and note the time of the dose, warfarin shouldn t be administered without either an INR or an X in the box. Hospital in-patient monitoring requirements are higher than outpatients as illness, drugs and changes in diet may affect the INR, suggested monitoring schedule is: WAHT-HAE-002 Page 7 of 43 Version 5.1

8 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet 1. Daily INR for very ill patients, those started on antibiotics, those with liver dysfunction and those who have had drugs started or stopped which are known to interact with warfarin (see Appendix 1 Interactions of the British National Formulary, further information can also be sought from Medicines Information ext 30235). 2. Every third day INR for patients not discussed in Outpatient style monitoring is suitable for long-term rehabilitation patients. Suggested dose changes for a target INR of 2.5: INR < Dose adjustment Increase by 20% Increase by 10% No change Decrease by 10% Decrease by 20% Drugs interacting with warfarin Prescribers and pharmacists must check the potential interaction of any medicine that is to be prescribed concomitantly with oral anticoagulants - see the latest edition of the BNF Appendix 1: Interactions or call the local Medicines Information Centre (ext 30235). Patients must be told to check any new or existing non-prescription medicines with the pharmacist or with a doctor if they are unsure. It usually takes between five to seven days for the drug to effect the INR. In patients who are stablised on warfarin and whose INR is within the target range on oral anticoagulants, control can be disrupted by: Initiating a new medicine which potentiates or inhibits the oral anticoagulant effect. Stopping an interacting medicine, the effect of which has already been compensated for through dose adjustment with the oral anticoagulant. For short courses (up to 5 days) of a new medicine, oral anticoagulant dose adjustment is not usually necessary but the dose of warfarin should be reduced or omitted over this timescale if a strongly potentiating medicine is prescribed. For longer courses of treatment, some initial alteration to the anticoagulant dose should be considered (especially if the INR is towards or at the upper limit) but in all cases, INR must be checked regularly after starting the new medicine and the oral anticoagulant dose adjusted accordingly. When the new medicine is stopped, a return to the previous maintenance dose may be needed. Antibiotics antibiotics may alter the gut flora changing the amount of vitamin K absorbed by the gut, therefore altering the INR. Patients starting antibiotics should have their INR more closely monitored. Alcohol - in regular amounts alcohol acts as a hepatic enzyme inducer and can result in an increase in the maintenance oral anticoagulant dose. However, pulsed alcohol excess can potentiate the anticoagulant effect in a dose-dependent way. Patients should be warned to drink only in moderation, to avoid binge drinking and to be reasonably consistent in their alcohol consumption. Variable alcohol intake is one of the commonest reasons for poor anticoagulant control. Diet - Major changes in diet (especially involving salads and vegetables) may affect warfarin control. Cranberry juice should be avoided. Refer to booklet/gp for further information on diet and lifestyle changes. WAHT-HAE-002 Page 8 of 43 Version 5.1

9 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Discharge arrangements Inadequate follow-up arrangements are a major cause of VKA incidents. When a patient is discharged on VKAs it is the duty of the discharging doctor to ensure that the patient, GP and anticoagulant clinic are fully informed of the follow-up arrangement for INR testing. The patient must be discharged with their warfarin book completed and the trust patient information leaflet Anticoagulation Therapy Monitoring. It is important if the patient is on drugs that potentially interact with warfarin that this information is passed onto the clinic taking over the warfarin dosing. Page 3 of the oral anticoagulation chart must be completed. There are three scenarios for discharge: 1. Patient newly started on warfarin. Initial follow-up is with the hospital for all patients. A follow-up appointment must be arranged by phoning ext 30863/ If the patient is discharged over the weekend this can be done on Monday morning, but it is unlikely there will be space for a clinic appointment that day so alternative arrangements may have to be made. Once follow-up arrangement has been made then page 3 of the anticoagulation chart must be completed in full and pages 1 to 3 faxed to the anticoagulant clinic on ext Patient established on warfarin normally attending the hospital anticoagulant clinic, same arrangements as above. 3. Patient established on warfarin normally managed by the GP. An appointment must be made for follow-up by the GP anticoagulant clinic. Page 3 of the anticoagulant chart must then be completed and pages 1-3 faxed to the GP practice. Pharmacy will not dispense warfarin without pages 1 to 3 of the anticoagulant chart being correctly completed. Patients in whom there has been a recent dose change or have had drugs that interact with warfarin started or stopped must have arrangements for a INR check in the first 3 days of discharge, this may mean them returning to the hospital for the INR check. Patients felt safe to be discharged with an INR greater than 4 should have an INR performed the following day. Information for Patients All patients discharged from hospital who are newly started on oral anticoagulants should be given: The yellow BSH/NPSA Oral Anticoagulant Therapy Record Book, completed with their recent INR results and doses. A copy of the Trust Anticoagulant service information leaflet for patients. A supply of 0.5mg, 1mg, and 3mg warfarin tablets (or appropriate phenindione tablets if this is used), depending on the patient s dose Verbal instructions about oral anticoagulant therapy. An appointment to have the next anticoagulant test / dose on an appropriate day. Reversal/stopping of VKAs including management of bleeding and a high INR This is summarized on page 4 of the oral anticoagulant chart. The reversal of warfarin is a balance between bleeding and thrombosis; the INR, presence of bleeding and the indication for anticoagulation should be considered. It should not be assumed that the bleeding is due to warfarin and other pathologies considered. Reversing the effects of warfarin in patients with a prosthetic valve should be discussed with cardiology/cardiothoracic surgery to decide on postreversal anticoagulation while anticoagulation for a thrombosis occurring less than 6 weeks previously should be discussed with the on-call haematologist. Atrial fibrillation and thrombosis more than 6 weeks previously can usually be safely reversed. There is no indication for the use of fresh frozen plasma (FFP) in the reversal of VKA. WAHT-HAE-002 Page 9 of 43 Version 5.1

10 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Stopping warfarin If warfarin is no longer required it can be stopped suddenly without any complications. Hospital in-patients who stop their warfarin need to be re-assessed for thromboprophylaxis. Management of high INRs without bleeding High INRs put the patient at increased risk of bleeding. An INR >8.0 should be treated with 1mg of vitamin K (iv or oral dependent on whether the patient can swallow and/or absorb the vitamin K) while an INR<8.0 can be managed by withholding the warfarin. The warfarin should be checked daily until it is in normal range then the warfarin re-introduced at a lower dose. If the INR goes sub-therapeutic then consideration should be made to introduce thromboprophylaxis (as discussed above in patients with a prosthetic heart valve the management of low INRs should be discussed with cardiothoracic surgery/cardiology). A rising INR despite vitamin K should be discussed with haematology. Intramuscular injections should be avoided in patients with a high INR. Management of bleeding in patients receiving VKAs Patients who are bleeding are classified as: Major bleeding life, sight or limb threatening bleeding. The patient should receive 10mg iv vitamin K. The on-call haematologist should be contacted to discuss the use of prothrombin complex concentrate (PCC) (Beriplex). If PCC is given then it is obtained from Blood Bank who will need the patients INR and weight. A post-infusion INR must be done minutes after the Beriplex to ensure adequate correction. Instructions on the administration of PCC are included with the drug. The side-effects of PCC are increased risk of thrombosis and theoretical risk of infection as it is a blood product. Minor bleeding. The patient should receive 2mg iv vitamin K. If there is ongoing bleeding the INR should be checked after 6 hours, otherwise rechecked the following day. Once the bleeding has subsided then consideration should be given to thromboprophylaxis (see above*). A rising INR despite vitamin K should be discussed with haematology. Intravenous vitamin K works in 4-8 hours while oral vitamin K 6-10 hours. IV vitamin K (Konakion MM) is mixed with 10ml 5% glucose and given over 3-5 minutes. Oral vitamin K is administered by drawing up the required volume of iv Konakion MM preparation in a syringe and diluting it with 5mls water, removing the needle and expelling the contents into the patient s mouth. Perioperative management of VKAs When planning for theatre the following factors must be considered: 1. Target INR required for the operation, these guidelines describes complete reversal of VKA, if anything less is required then it should be discussed with haematology. 2. Indication for the VKA (atrial fibrillation, treatment of thrombosis, heart valves) 3. When is the operation required - Urgent (within six hours), soon (more than six hours) or planned The first question is whether the surgery can be delayed if the indication for the VKA is temporary. Once surgery is complete there is no reason why patients cannot be discharged on LMWH with follow-up to ensure safe recommencement of warfarin. Warfarin is best recommenced at the patients normal dose, there is no need for a loading dose. Patients who fail to respond to standard reversal procedures should be discussed with haematology. WAHT-HAE-002 Page 10 of 43 Version 5.1

11 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Urgent procedure within 6 hours Indication for VKA Atrial Fibrillation Valve replacement Recent thrombosis within 6 weeks Thrombosis more than 6 weeks ago Give 10mg iv vitamin K and consider PCC. After surgery start prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. Discuss case with cardiology/cardiothoracic surgery Discuss case with haematology Give 10mg iv vitamin K and consider PCC. After surgery start prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. Soon procedure Indication for VKA Atrial Fibrillation Valve replacement Recent thrombosis within 6 weeks Thrombosis more than 6 weeks ago Give 10mg iv vitamin K and recheck INR prior to surgery. After surgery start prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. Discuss case with cardiology/cardiothoracic surgery Discuss case with haematology Give 10mg iv vitamin K and recheck INR prior to surgery. After surgery start prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. WAHT-HAE-002 Page 11 of 43 Version 5.1

12 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Routine proceedure Indication for VKA Atrial Fibrillation Valve replacement Recent thrombosis within 6 weeks Thrombosis more than 6 weeks ago Stop warfarin four days prior to procedure. To reduce the need to cancel surgery the INR should be checked, if possible, the day before surgery: if still >2.0 then 1mg oral vitamin K should be given then INR rechecked prior to surgery the next day. If INR cannot be checked the day before it must be checked prior to surgery, if it is still too high and the surgery can be delayed then 1mg iv vitamin K could be given and INR rechecked after 4 hours. Restart prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. Discuss case with cardiology/cardiothoracic surgery Discuss case with haematology Stop warfarin four days prior to procedure. To reduce the need to cancel surgery the INR should be checked, if possible, the day before surgery: if still >2.0 then 1mg oral vitamin K should be given then INR rechecked prior to surgery the next day. If INR cannot be checked the day before it must be checked prior to surgery, if it is still too high and the surgery can be delayed then 1mg iv vitamin K could be given and INR rechecked after 4 hours. Restart prophylactic LMWH when haemostasis is secure. Restart warfarin when swallowing and continue LMWH until INR therapeutic for 2 days. Other side-effects of VKA Apart from bleeding there are very few side-effects of VKA. The other major side-effect is warfarin induced skin necrosis which presents as painful, black necrotic skin patches. Skin necrosis is due to very low levels of protein C and S in patients who are homozygous for protein C or S deficiency. Advice should be sought from clinical haematology. Rashes and allergic type reactions occasionally occur. Warfarin resistance is very rare and is usually due to non-compliance, resistance should be considered in patients who fail to achieve a therapeutic INR despite supervised doses of warfarin greater than 20mg per day. Possible cases of resistance should be discussed with clinical haematology. VKAs are teratogenic in the first trimester of pregnancy and patients on warfarin are encouraged to present immediately if they feel they are pregnant. Women are normally managed on LMWH for their pregnancy except for some high risk valves which require unfractionated heparin for the first trimester. WAHT-HAE-002 Page 12 of 43 Version 5.1

13 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet The new oral anticoagulants Detailed guidance on who should receive dabigatran, apixaban and rivaroxaban in atrial fibrillation has been produced by the department of cardiology, it is found at the NHS Worcestershire website. Detailed guidance on the use of rivaroxaban in patients with DVTs or suspected DVTs can be found in appendix 2, these are also available on the trust intranet website. This also includes a patient information leaflet and a flow chart to determine who may be eligible. Direct thrombin inhibitors Dabigatran Dabigatran is an oral direct thrombin inhibitor which is usually given with twice daily dosing. It is licensed and NICE approved for the prevention of stroke and systemic emboli in patients with atrial fibrillation and the prevention of thrombosis following hip and knee replacements. The effect of dabigatran cannot be routinely measured and it cannot be reversed. A normal coagulation profile may indicate that the anticoagulant effect of the drug has worn off. Because of its predictable pharmacokinetics it is a single dose for all patients: Atrial fibrillation 150mg bd standard and 110mg bd in those felt to be at high risk of bleeding (aged >75, renal dysfunction, previous bleeds, taking verapamil, quinidine or amiodarone and/or history of gastro-oesphageal reflux)). Prevention of DVT/PE following hip or knee replacement 110mg 1-4 hours after surgery (75mg in over 75 s) and then 220mg daily (150mg in those also on verapamil or amiodarone) for 9 days (knee) and days (hip) Dabigatran is contra-indicated in patients who have a GFR<30, liver enzymes >2 upper limit of normal and taking systemic ketonazole, cyclosporine, itraconazole or tacrolimus. The side-effect profile is greater than that of warfarin and a full list is found on the summary of product characteristics ( Detailed guidance on who should receive dabigatran in atrial fibrillation has been produced by the department of cardiology, it is included in appendix 2. Initiating dabigatran If the patient is not on any anticoagulants then dabigatran can be started immediately. Patients on VKAs should stop their VKA and start dabigatran when the INR<2.0. Patients on LMWH should stop the LMWH and start dabigatran 2 hours before their next dose of LMWH would be due. If the patient has been started on the drug while an inpatient they should be discharged with a standard discharge pack, to be continued by the GP. If it is recommended in outpatients for the patient to start then the request form should be sent to the GP requesting the drug to start. Patients on dabigatran are not managed through the hospital anticoagulation service. WAHT-HAE-002 Page 13 of 43 Version 5.1

14 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Management of patients on dabigatran undergoing surgery Elective surgery Dabigatran has a half life of approximately 13 hours, but this extends in patients with renal impairment. The presence of a normal coagulation screen suggests only minimal effect of the drug remains. Discontinuation is advised as below: Timing of last dose prior to surgery Renal function (GFR) Half life of dabigatran Standard risk of (ml/min) (hours) bleeding High risk of bleeding >80 ~13 24 hours 2 days ~15 2 days 3 days ~18 3 days 4 days < days 5 days Epidural and spinal anaesthesia may require a longer time from last dose. The drug can usually be restarted the following day when complete haemostasis has been secured but if there is concern over bleeding then re-introduction should be delayed, bridging therapy with low molecular weight heparin may be required if there is a >24 hour delay. Emergency surgery If patient requires emergency surgery ideally it should be delayed as long as clinically possible to allow maximal reversal of the dabigatran. Prior to surgery the blood bank should be informed to allow time for crossmatching of blood, platelets and the thawing of FFP for use if there is excessive bleeding during surgery. If the patient has taken dabigatran within 2 hours activated charcoal may reduce the absorption and should be considered if there is no anaesthetic contraindication. When surgery does take place, if there is bleeding, then there should be early use of blood, platelets and FFP. Where life-threatening bleeding is present the use of recombinant activated factor VIIa (NovoSeven) or prothrombin complex concentrate (Beriplex) should be considered. Epidural or spinal anaesthesia should be avoided. Consideration should be given to the use of tranexamic acid (contra-indicated in urinary tract bleeding). There is no indication for the routine use of FFP or platelets without major haemorrhage as these will not reverse the effects of the drug. Management of bleeding on dabigatran Where there is minor bleeding then the next dose of dabigatran should be withheld and local measures taken to stop the bleeding. Moderate and severe bleeding should be treated with local measures, early surgical/radiological interventions, blood product support (blood bank must be informed of a patient bleeding on dabigatran), and the consideration of activated charcoal if the last dose was less than two hours previously. Life, limb or sight threatening bleeding should be treated as severe bleeding but the use of recombinant activated factor VIIa (NovoSeven) or prothrombin complex concentrate (Beriplex) should also be discussed with a haematologist In the absence of contra-indications consideration should be given to the use of tranexamic acid in all bleeding patients (contra-indicated in urinary tract bleeding). WAHT-HAE-002 Page 14 of 43 Version 5.1

15 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet As dabigatran is renally excreted a good urine output should be maintained. Haemofiltration may remove the drug quicker and may be considered if there is bleeding or if emergency surgery is required. More detailed reviews can be found at: van Ryan et al. Dabigatran etexilate a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity. Thrombosis and Haemostasis. 2010; 103: and Hankey G, et al. Dabigatran Etexilate: A New Oral Thrombin Inhibitor. Circulation. 2011;123: Oral factor Xa inhibitors Rivaroxaban and Apixaban Rivaroxaban and apixaban are oral factor Xa inhibitors. Rivaroxaban is licensed and NICE approved for the prevention of stroke and systemic emboli in patients with atrial fibrillation, the prevention of DVT or PE following hip or knee replacement and for the treatment of DVT and PE. Apixaban is licensed and NICE approved for the prevention of stroke and systemic emboli in patients with atrial fibrillation and the prevention of DVT or PE in patients following hip and knee replacement. Rivaroxaban Unlike warfarin rivaroxaban has several side-effects other than bleeding, these can be found at the SPC Rivaroxaban is given at a dose of 20mg once a day for the treatment of AF. New DVTs or PEs are initially treated with 15mg twice a day for three weeks then 20mg once per day after that, if the patient is already established on an anticoagulant then they should be started on 20mg once per day. For those patients following hip or knee replacement a dose of 10mg daily is used. Patients already on a VKA can stop the VKA and start rivaroxaban when INR<2.5. Patients on treatment dose low molecular weight heparin can start rivaroxaban 0-2 hours before the next dose of heparin is due. For atrial fibrillation if the patient has been started on the drug while an inpatient they should be discharged with a standard discharge pack, to be continued by the GP. If it is recommended in outpatients for the patient to start then the request form should be sent to the GP requesting the drug to start. For suspected DVTs then a standard five day (ten tablet) pack will be provided. If the DVT is confirmed the patient should attend their GP for continuation of the medication. The drug should be stopped if no DVT is found. Patients on rivaroxaban are not managed through the hospital anticoagulation service. Apixaban Unlike warfarin apixaban has several side-effects other than bleeding, these can be found at the SPC Apixaban is given at a dose of 5mg twice a day for the treatment of AF. For those patients following hip or knee replacement a dose of 2.5mg twice a day is used. Patients already on a VKA can stop the VKA and start apixaban when INR<2.0. Patients on treatment dose low molecular weight heparin can start apixaban 0-2 hours before the next dose of heparin is due. For atrial fibrillation if the patient has been started on the drug while an inpatient they should be discharged with a standard discharge pack, to be continued by the GP. If it is recommended in outpatients for the patient to start then the request form should be sent WAHT-HAE-002 Page 15 of 43 Version 5.1

16 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet to the GP requesting the drug to start. Patients on apixaban are not managed through the hospital anticoagulation service. Elective surgery Rivaroxaban has a half life of approximately 5-13 hours, but this extends in patients with renal impairment and the elderly. Apixaban has a similar half life but has less renal excretion. A normal coagulation profile may indicate that the anticoagulant effect of the drug has worn off. Discontinuation is advised as below: Renal function (CrCl) (ml/min) Increase in rivaroxaban concentration Timing of last dose of apixaban or rivaroxaban prior to surgery Standard risk of bleeding High risk of bleeding >80 1.0x 24 hours 2 days x 2 days 3 days x 3 days 4 days <30 1.6x 5 days 5 days Epidural and spinal anaesthesia may require a longer time from last dose. The drug can usually be restarted the following day when complete haemostasis has been secured but if there is concern over bleeding then re-introduction should be delayed, bridging therapy with low molecular weight heparin may be required if there is a >24 hour delay. Emergency surgery If patient requires emergency surgery ideally it should be delayed as long as clinically possible to allow maximal reversal of the rivaroxaban. Prior to surgery the blood bank should be informed to allow time for crossmatching of blood, platelets and the thawing of FFP if there is excessive bleeding during surgery. When surgery does take place, if there is bleeding, then there should be early use of blood, platelets and FFP. Where life-threatening bleeding is present the use of prothrombin complex concentrate and/or recombinant factor VIIa (NovoSeven) should be considered. Epidural or spinal anaesthesia should be avoided. Consideration should be given to the use of transexamic acid (contra-indicated in urinary tract bleeding). There is no indication for the routine use of FFP or platelets without major haemorrhage as these will not reverse the effects of the drug. Bleeding Where there is minor bleeding then the next dose of rivaroxaban should be withheld and local measures taken to stop the bleeding. Moderate and severe bleeding should be treated with local measures, early surgical/radiological interventions, blood product support (blood bank must be informed of a patient bleeding on rivaroxaban). Life, limb or sight threatening bleeding should be treated as severe bleeding but the use of recombinant activated factor VIIa (NovoSeven) or prothrombin complex concentrate should also be considered. WAHT-HAE-002 Page 16 of 43 Version 5.1

17 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Consideration should be given to the use of transexamic acid in all bleeding patients (contraindicated in urinary tract bleeding). There is no indication for renal dialysis to try and reverse the effects of rivaroxaban. More information can be found on the Summary of Product Characteristics Information for Patients All patients discharged from hospital who are newly started on the new oral anticoagulants should be given: The appropriate Patient Information booklet. These are supplied by the manufacturer. A supply of tablets, depending on the patient s dose Verbal instructions about oral anticoagulant therapy. WAHT-HAE-002 Page 17 of 43 Version 5.1

18 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet ANTICOAGULANT CLINIC PROCESS MAP - HOSPITAL DOSED PATIENTS Patient is referred to the Anticoagulant Clinic by the Ward, Consultant or GP Wards telephone ACC Clerk and book appointment for Wed or Fri a.m. and send referral and inpatient Warfarin chart Consultants & GPs send in a referral letter. Patient is sent an appointment letter with a blood form for FBC, INR & PT week before appt. New patient appointments are booked onto OASIS by ACC Clerk. Yellow books go to the booking-in staff to be entered on WinPath. This is a new requirement to meet the NPSA safety alert on oral anticoagulation. The Yellow book has Sample ID & quality is checked. Sample is sent with sufficient ID and this is obviously the same each episode Sample is numbered & barcoded yellow book to the ensuring integrity of patient record. Any messages from sample number is stuck on yellow laboratory for testing. patients are kept with the book but not dealt with at this book. (Previous numbers should be Yellow books are easy to point. Test Format Code requested is ID (INR for dosing). covered, removed or rendered nonreadable). spot and can be fast Samples are being centrifuged during this process. tracked if required. New patients see ACC Nurse & are given yellow book & pack, prescription, dose and next appt. date. Patient demographics & treatment plan are entered onto DAWN. Ward discharges have an INR test and next appt. date. Existing patients present yellow book at GP surgery or Phlebotomy. Yellow book is sufficient to identify patient & which sample is required. Samples are analysed and results sent to WinPath in the normal way. Only those high or low go onto the fail queue, the rest auto-authorise. BMS will review the fail queue and repeat any necessary before authorising. Lab staff enter the INR result into the yellow books. This is a simple process using the barcodes on the books to access the result. There is no need to keep yellow books in numerical order. Yellow books are passed to the dosing team along with any other correspondence submitted. WAHT-HAE-002 Page 18 of 43 Version 5.1 Dosing team periodically run the upload of INR results from WinPath to DAWN. They review each patient, enter any relevant new information, review calculated dose and suggested next appointment and amend as necessary. Dose and next appointment are written in yellow book.

19 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet Anticoagulant Clinic Clerk reschedules the DNAs on DAWN. Persistent DNAs are followed up by letter or telephone call to the patient in the first instance and then to GP if still fail to attend. At the end of the day, the lab staff run the upload of dosing information and next test date from DAWN to WinPath. WinPath then sends this information across the Yellow books are put into window envelopes and posted back to the patient. (Address labels on yellow books show through window). Patient is telephoned directly if there are any queries of if they need to be informed of urgent dose changes. GP links. WAHT-HAE-002 Page 19 of 43 Version 5.1

20 It is the responsibility of every individual to ensure this is the latest version as published on the Trust Intranet ANTICOAGULANT CLINIC PROCESS MAP - GP DOSED PATIENTS Induction is carried out If GP intends to dose Patient is bled and the Sample is treated like all The INR does not upload to by Hospital patient long term, they sample is sent in with a other samples in the DAWN and is simply reported Anticoagulant Clinic are handed over once standard Haematology laboratory. Test Format by the usual WinPath channels Nurse as per the stable. Patient record is request form for INR Code requested is I (INR back to the GP who then pathway described. suspended on DAWN. testing. (Yellow book is no dose). decides dose and arranges not sent in). next test. N.B. Whilst patient is being dosed by the GP, we do not keep any INR/dose/appointment information on DAWN. GP will keep patient s yellow book up-to-date so that should the patient be referred back to the Anticoagulant Clinic, the full history is available. Some practices also perform their own INR testing, in which case there is no laboratory involvement, although practices may refer an INR sample for confirmation if a rogue result is obtained using near patient testing. WAHT-HAE-002 Page 20 of 43 Version 5.1