ANTICOAGULATION GUIDELINES (Revised July 2005)
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1 ROYAL HOBART HOSPITAL ANTICOAGULATION GUIDELINES (Revised July 2005) To contact on-call Haematologist: Call switch (extension 9 or ) Endorsed by The Southern Tasmanian Division of General Practice DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
2 Index Risk of Venous Thromboembolism (VTE) RHH Risk assessment for the use of thromboprophylaxis for VTE in medical patients Unfractionated heparin Guidelines for the use of unfractionated heparin Reversal of unfractionated heparin with protamine Partial reversal of LMWH with protamine Warfarin Initiation of warfarin therapy Prescribing, administration and monitoring Target INRs Discharge instructions Warfarin loading protocol - Age/disease adjusted Management of over-anticoagulation with warfarin Warfarin reversal pre-elective procedure Anticoagulation in patients with chronic or paroxysmal non-valvular atrial fibrillation Hypercoagulability testing Appendix A1: Anticoagulants for use at the Royal Hobart Hospital A2: Contraindications to anticoagulant therapy A3: Bleeding risk with anticoagulation A4: Medications that interfere with the effect of warfarin This document was produced in collaboration with the Departments of Haematology, Pharmacy, Cardiology and General Internal Medicine. Any adverse drug events related to patients using these guidelines, or comments should be reported to the Drug Utilisation & Evaluation Pharmacist (Catherine Drake), on ext: Disclaimer: This document has been developed by the Royal Hobart Hospital specifically for its own use. Use of this document and any reliance on the information contained therein by any third party is at his or her own risk and the Royal Hobart Hospital assumes no responsibility whatsoever. DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
3 RHH Risk Assessment for the use of Thromboprophylaxis for Venous Thromboembolism in Medical Patients Patients with a projected length of stay of more than 2 days ASSESS RISK ONE OR MORE OF THE FOLLOWING RISK FACTORS > 40 years with Acute Heart Failure > 40 years with Acute Respiratory Failure > 40 years with Adenocarcinoma Recent Ischaemic Stroke Thrombophilia Prior Venous Thromboembolism (DVT or PE) Active Systemic Lupus Erythematosus OR ONE OR MORE OF: Acute Infection Active Autoimmune Disease (Rheumatoid Arthritis) Acute Episode of Inflammatory Bowel Disease Trauma/Burns Recent Surgery PLUS ONE OR MORE OF: Age > 75 Active cancer Obesity Varicose Veins Hormone Therapy (including HRT) Congestive Heart Failure COPD Immobility NO RISK FACTORS PRESENT OR ANY OTHER MEDICAL CONDITION RENDERING PATIENT HIGH RISK VTE ENOXAPARIN 40 MG sc daily (20mg daily if diminished renal function) FOR 6 14 DAYS OR UNTIL DISCHARGE NO PHARMACOLOGICAL PROPHYLAXIS RECOMMENDED Early mobilisation and maintenance of adequate fluid intake are recommended for all patients if possible. Physical methods of prophylaxis (e.g. TED stockings) are indicated for use in patients with a contraindication to heparins and may be used in conjunction with enoxaparin if deemed necessary by the treating physician. The prophylactic dose of enoxaparin should be reduced to 20 mg once daily for patients with diminished renal function (estimated creatinine clearance < 30 ml/min). Platelet count should be measured at baseline and after 5 days of dosing with enoxaparin and periodically thereafter. Physicians should re-assess the need for ongoing prophylaxis after 14 days. FOR FURTHER INFORMATION CONTACT ONCALL HAEMATOLOGIST VIA SWITCH (Ext 9 or ). These guidelines are intended to assist patient management and the specific treatment of individual patients should be DOC decided ID# = in 3532 conjunction Issued with by Dr the Kate caring Burbury Physician. : October 2005 : Expires October
4 Guidelines for the use of intravenous unfractionated STEP I: Check baseline coags STEP 2: Give LOADING DOSE of heparin: 5000units IV STEP 3: Make up heparin infusion: 25,000units heparin in 500mL normal saline (50U/mL) STEP 4: Start infusion initial rate: 21mL/hr STEP 5: Check APTT 4-6 hours after commencement of infusion Aim for APTT X normal (50-80secs) Continue infusion or adjust rate as indicated below Repeat APTT 4-6 hours after any adjustment in heparin dosage Once APTT therapeutic, check daily STEP 6: Check Hb and platelets on day 3, 7 and 10 (to detect bleeding, HITs- see below) Consult haematologist IF Baseline APTT is abnormal APTT remains <40secs after first dose adjustment Any further advice is required Table: Heparin adjustment nomogram continue or adjust infusion as indicated below APTT (secs) Bolus (units) Pause (mins) Rate change (ml/hr) Dose change (units/hr) Next APTT < hrs hrs Next am hrs hrs > hrs REVERSAL OF UNFRACTIONATED HEPARIN WITH PROTAMINE 1mg of protamine will neutralise 100units UFH PARTIAL REVERSAL OF LMWH (i.e. Enoxaparin) WITH PROTAMINE Time since last dose of LMWH <8 h: 1mg Protamine per mg of enoxaparin 8-12 h: 0.5mg Protamine per mg of enoxaparin >12 h: reversal not necessary Use of protamine: Administer as slow IV push over 10 mins Rapid administration can cause hypotension and anaphylactoid reactions Onset of action, neutralisation of UFH, 5 mins Excessive doses (>100mg) can cause paradoxical anticoagulation For full details see Product Information HITs: Heparin induced thrombocytopenia syndrome = fall in platelet count >50% from baseline or to <100x10 9 /L, after commencing heparin/heparinoid therapy. Contact Haematologist. DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
5 Initiation of warfarin therapy There are two brands of warfarin - Marevan and Coumadin. They are not equivalent and should not be used interchangeably. Marevan is the preferred brand at the RHH and is readily available on ward impress Marevan will be prescribed for all inpatients commencing warfarin. Patients already on Coumadin brand, should use their own tablets or have them ordered specifically from pharmacy. PRESCRIBING AND ADMINISTRATION Baseline INR must be obtained (LFTs are also recommended). Commence warfarin on same day as heparin therapy (unless contraindicated). overlap warfarin/heparin therapy for at least 4 days and INR >2.0 for hours. See warfarin loading protocol for appropriate dosing and monitoring of warfarin. Warfarin is to be administered at 1600 hours and should be prescribed before that time. write the order in the designated warfarin section of the drug chart Patient should be provided with written and verbal instructions (usually by pharmacist). MONITORING Monitor INR daily, adjust warfarin dose as indicated, until INR therapeutic and stable. Blood should be collected in the morning, so INR is available prior to 1600 dosing TARGET INR Low risk mechanical/prosthetic heart valve: High risk mechanical/prosthetic heart valve: All other indications (e.g. VTE, AF): DRUG INTERACTIONS AND BLEEDING RISK Certain drugs (and comorbidities) may increase or decrease the effect of warfarin, or increase the bleeding risk (see Appendix 3 and 4). The INR must be checked regularly (1-2days) when starting or stopping any of the drugs listed, particularly antibiotics. INR GREATER THAN THERAPEUTIC RANGE See Management of over-anticoagulation and Warfarin reversal guidelines (page 7) Contact Haematologist if INR>6 and/or there is any bleeding DISCHARGE INSTRUCTIONS It is vital to provide appropriate information to the patient and the GP so that INR can be stabilised and monitored. The discharging medical officer is responsible for: Ensuring that the patient has received adequate counselling and education about warfarin therapy. The patient should also be provided with a warfarin booklet for a personal record (usually pharmacist completes dosing history and counsels patient). Contacting the GP on day of discharge to arrange appropriate INR monitoring. The warfarin therapy chart should be faxed to the GP with the completed discharge summary. The following information should be included in discharge summary: 2. The indication for warfarin therapy 3. Target INR 4. Planned duration of therapy 5. Date warfarin was initiated and dosing history (should be provided on warfarin chart) 6. Brand of warfarin prescribed 7. Relevant investigations, including thrombophilia testing if done. DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
6 Warfarin Loading Protocol Dose for age (mg) Day 1** INR <65 years* 65 years OR significant medical conditions* < Monitoring Baseline INR & LFTs (If on heparin therapy and APTT > 80 seconds, INR may be falsely elevated) 1.2 If baseline INR 1.2 seek specialist physician or haematologist advice prior to warfarinisation. Day 2** Day 3 Day 4 < < > < > INR (in AM) Daily INRs (in AM) until INR is within the target range for 2 consecutive days. If patient is discharged prior to stabilisation, daily monitoring should be continued by the GP. GP & patient need to be informed of requirement for monitoring. GPs can contact RHH Haematologists for advice on warfarin stabilisation. Day 5 + Use Day 4 protocol as a guide If INR remains low (<2.0) then increased doses may be needed (Consult Haematology for advice). * Significant medical conditions: heart failure, liver disease, severe infection, reduced oral intake, broad-spectrum antibiotics. ** NOTE: Reduce dose by at least 30% for the first 2 days if on amiodarone or sulphonamide antibiotics (including cotrimoxazole). DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
7 Warfarin Reversal Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. MJA 2004; 181 (9): To reverse the effects of over-anticoagulation with warfarin, vitamin K should always be given. Fresh frozen plasma (FFP) or prothrombin complex concentrate (Prothrombinex) achieves a more immediate result, however it is short-lived - vitamin K is essential for sustaining the reversal achieved. Management of OVER-anticoagulation with warfarin therapy Target INR INR No bleeding Management Bleeding Withhold warfarin Monitor INR until therapeutic 5-10 Withhold warfarin Vitamin K: 1-2mg orally/iv >10 Withhold warfarin Vitamin K: 2.5-5mg orally/1-3mg IV Cease warfarin therapy Give Vitamin K IV: INR : 1-3mg INR 5-10: 3-5mg Life threatening bleeding: 3-5mg AND consider Prothrombinex/FFP with haematology consultation Consider the need for ongoing anticoagulation, when selecting vitamin K dose. Vitamin K should be given orally or slow intravenous (avoid IM). Recheck INR 4-6h post -vitamin K IV (full effect of oral takes up to 24h) - and then monitor daily until therapeutic Consider reasons for increased INR and warfarin dose reduction. To achieve NORMAL pre-procedure INR (<1.4) INR Non-urgent Management Urgent Withhold warfarin night prior to procedure Give vitamin K 2mg IV 6hrs prior to procedure Check INR 1hr prior to procedure Restart warfarin day of procedure at previous maintenance dose OR Withhold warfarin 4 days prior to procedure Consider bridging anticoagulation therapy (UFH, LMWH) Check INR night prior to procedure, give vitamin K as needed Give vitamin K (as above) Consider Prothrombinex/FFP Consult Haematologist >4 Follow the above guidelines and consult Haematologist Low risk procedures that do not require normalisation of INR (INR must be within in therapeutic range): simple dental procedures or periodontal therapy dermatological procedures where external pressure can be applied. With any uncertainty, consult Haematologist (via RHH switchboard) See also flowchart: Management of over-anticoagulation with warfarin therapy (page 9) DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
8 FLOWCHART: MANAGEMENT OF OVER- ANTICOAGULATION WITH WARFARIN THERAPY To be used in conjunction with table (page 7) Elevated INR (>3.5) Withhold warfarin Assess bleeding risk Monitor INR daily until therapeutic Consider reasons for elevated INR Bleeding No bleeding Vit K Prothrombinex +/-FFP Contact haematologist INR Vit K not required INR 5-10 Vit K 1-2mg IV/orally INR >10 Vit K 1-3mg IV or 2.5-5mg orally DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
9 Warfarin reversal pre-elective procedure Patient identification sticker Medical indication for warfarin: Procedure to be undertaken: Planned date of procedure: / / Current (maintenance) dose of warfarin: mg Most recent INR: Date: / / Tick boxes and complete details, where appropriate, when task completed Yes No Warfarin withheld 24 hours prior to procedure, date: / / INR checked 6 hours prior to procedure result: If INR 2.0, give 2mg Vitamin K IV; If INR 3.0 ring Haematologist-on-call. Vitamin K given, if so dose: mg oral intravenous INR checked 4 hour post-vitamin K administration result: If INR 2.0 ring Haematologist-on-call. Surgery completed as scheduled Complications peri-operatively, if so give details: If possible, please complete details after procedure Warfarin restarted post procedure, date: / / INR checked prior to discharge result: Arrangements made for ongoing INR monitoring with LMO Please file form with patient surgical/anaesthetic admission notes DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
10 Anticoagulation in patients with Chronic or Paroxysmal Non-Valvular Atrial Fibrillation Risk factors (RF) for stroke in patients with AF Previous TIA or stroke Hypertension Heart failure LVEF 35% Previous systemic embolic event IHD Structural heart disease Diabetes Atrial fibrillation 65 years years >75 years Additional risk factor(s) present No Yes aspirin warfarin* warfarin* The choice of treatment is ultimately a clinical decision and should be made in conjunction with the caring Physician. If warfarin cannot safely be used, then low dose aspirin should be considered. In patients clinically assessed to be at low risk, echocardiography should be considered. Risk increases as left atrial size increases and left ventricular function decreases. Therapeutic range (INR) in general should be kept between 2.0 and 3.0. * The benefit-to-risk ratio of warfarin therapy in the elderly (age > 75 years) and those with bleeding risk factors (see appendices 2 and 3) may be decreased. Caution should be used when applying these guidelines to such populations. For Complete guidelines see: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Antithrombotic therapy in atrial fibrillation. Chest 2004;126:429S-456S DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
11 Hypercoagulability Testing Tests for inherited conditions are not usually appropriate in the absence of a family history. Current recommendations for testing are outlined by the following flow chart. Spontaneous/idiopathic VTE OR History of recurrent VTE Family history? Yes No Activated protein C resistance Prothrombin mutation Antiphospholipid antibodies 2 Plasma homocysteine Factor VIIIc Antithrombin 1 Protein C 1 Protein S 1 Activated protein C resistance Prothrombin mutation Antiphospholipid antibodies 2 Plasma homocysteine Factor VIIIc 1 Results can be affected by acute thrombosis, therefore avoid testing during the acute presentation. Protein C and Protein S tests cannot be accurately performed whilst patient is on warfarin therapy. Heparin may lower Antithrombin III levels. 2 Antiphospholipid antibodies testing requires both lupus anticoagulant and anticardiolipin antibodies NOT recommended to screen patients who have sustained a VTE in the following settings: Recent major surgery/trauma/immobilisation Active malignancy Heparin-induced thrombocytopenia Pre-eclampsia at term UNLESS previous unprovoked VTE or strong family history of VTE For these tests, the following venous blood samples are required: 2 x 4mL sodium citrate (blue tops) 1 x SST (red top with gel) and For homocysteine 1x EDTA (pink top) sent immediately to the lab on ice. See RHH Intranet: Pathology test and specimen collection for further information. DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
12 Appendix Appendix 1: Anticoagulants available for use at Royal Hobart Hospital Anticoagulant Monitoring Half-life Excretion Indications (hours) Oral preparations Warfarin INR Liver Dindevan INR 6 Liver Allergy to warfarin Parenteral preparations Unfractionated heparin APTT 1-2 Liver Enoxaparin (Clexane) Anti-Xa units 4-7 Renal Fragmin (Dalteparin) Anti-Xa units 2-5 Renal Allergy to enoxaparin Danaparoid (Orgaran) Anti-Xa units Renal HITTs Fondaparinux Anti-Xa units Renal Orthopaedic surgery; HITTs Lepirudin APTT 1 Renal HITTs Appendix 2: Contraindication to and/or precautions for the use of anticoagulants Conditions with high risk of uncontrolled bleeding: Major bleeding diathesis (e.g. coagulation defects, thrombocytopenia platelet count < 40) Uncontrollable active bleeding state Haemorrhagic stroke in the acute phase Cerebral lesions at high risk of bleeding Active ulcerative or angiodysplastic gastrointestinal disease Proliferative diabetic retinopathy Severe uncontrolled hypertension Severe renal and/or hepatic dysfunction Anticoagulation should be used with caution in some types of surgery/procedures Neurosurgery (brain and spinal) Ophthalmic surgery Neuroaxial anaesthesia (epidural and spinal) DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
13 Appendix 3: Bleeding risk and Warfarin (or Dindevan) Related to the degree of anticoagulation, risk increases substantially at INR>4.0. Factors associated with increased risk of bleeding: Age 65 years - Dementia, confusion - Poor mobility, frequent falls Hypertension (SBP>180mmHg; DBP>100mmHg) Acute or chronic alcoholism; chronic liver disease Poor compliance Presence of bleeding diathesis Presence of potentially bleeding lesions (peptic ulcer disease, angiodysplasia) Concomitant use of NSAIDs, antibiotics Instability of INR control Factors associated with increased INR (INR 6.0) Diarrhoea Fever Impaired liver function Worsening heart failure Concomitant drug therapy that interacts with warfarin metabolism (see Appendix 4) Appendix 4: Medications that interfere with the effect of warfarin Increased anticoagulant effects Amiodarone Antimicrobials (cephalosporins, ciprofloxacin, norfloxacin, macrolides, metronidazole, tetracycline, sulfonamides, azole antifungals, isoniazid) Allopurinol Cimetidine, omeprazole SSRIs Paracetamol, celecoxib, diclofenac, sulfinpyrazone Cholestyramine, colestipol, statins, gemfibrozil Anabolic steroids Decreased anticoagulant effects Antithyroid hormones: PTU, carbimazole, Antiepileptics: carbamazepine, phenytoin, barbituates Griseofulvin, rifampicin Oral contraceptives Vitamin K (inc nutritional supplements) Duiretics: spironolactone Corticosteroids Increased bleeding tendency Antiplatelet drugs: NSAIDs, salicylates (aspirin), clopidogrel, ticlopidine, dipyridamole, tirofiban Ulcerogenic drugs: corticosteroids, NSAIDs, salicylates Other anticoagulants DOC ID# = 3532 Issued by Dr Kate Burbury : October 2005 : Expires October
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