Leeds Children s Hospital Guidelines for Anticoagulation in Paediatric Cardiac Patients SURGICAL PATIENTS Preoperative Management Blalock-Taussig (BT) Shunt / Fontan circulation / Sano Shunt and Severe cyanosis Receiving Aspirin / Dipyridamole / Clopidogrel Stop aspirin / dipyridamole 2 days prior to surgery (i.e. if the child s operation is on Tuesday, then their last dose of aspirin / dipyridamole will be on Saturday). Admit the day before for intravenous fluids +/- intravenous heparin depending on the haematocrit. It is significant if it is greater than 0.65. Start heparin (prophylactic) at 10units/Kg/hour. Check APTT at 4 hours, if below 85 continue at same rate. At the unlikely event of APTT greater than 85 stop heparin and recheck APTT in 1hour. Discuss results with paediatric cardiology consultant/registrar. Check APTT daily, 4 hours after syringe changes. MVR / AVR on Warfarin Stop warfarin 2 days prior to surgery (i.e. of the child s operation is on Tuesday, then their last dose of warfarin will be on Saturday). The INR will need to be checked on the day of admission, the day before the operation. If the INR is between 1.5-2.2, then no further anticoagulation treatment is required prior to the operation. However if the INR is less than 1.5 then a stat dose of therapeutic tinzaparin (see page 9) should be given that evening, the day before the operation. Check APTT daily, 4hours after syringe changes Fontan Circulation on Warfarin Stop warfarin 2 days prior to surgery (i.e. of the child s operation is on Tuesday, then their last dose of warfarin will be on Saturday). Note: Stop Heparin Infusion 6hrs prior to surgery Post operative Management Blalock-Taussig Shunt (BT) / Sano Shunt / Hybrid procedure stent THIS IS STANDARD TREATMENT (Any deviations from this will be decided by the surgeon and documented clearly) Start prophylactic Heparin (see page 7) 2 hours post operation, unless there are bleeding issues. Start heparin (prophylactic) at 10units/Kg/hr (No loading dose) Check APTT after 4hrs, if less than 85 continue at the same rate. In the unlikely event that the APTT is greater than 85 discuss with surgeon or intestivist. Check APTT daily, 4 hours after syringe change. Start aspirin once patient tolerating feeds. Overlap heparin and aspirin until the 2 nd dose of aspirin is given (24hrs) and then stop the heparin. 1
Fontan Completion THIS IS STANDARD TREATMENT (Any deviations from this will be decided by the surgeon and documented clearly) Start prophylactic Heparin (see page 7) 2 hours post operation, unless there are bleeding issues. Start heparin (prophylactic) at 10units/Kg/hr (No loading dose) Check APTT after 4hrs, if less than 85 continue at the same rate. In the unlikely event that the APTT is greater than 85 discuss with surgeon or intestivist. Check APTT daily, 4 hours after syringe change. The day after surgery stop the heparin and after 2 hours start therapeutic treatment of subcutaneous tinzaparin (therapeutic) (see page 9). Antifactor Xa monitoring is required and dosage adjustment will be required as per levels (see page 8). Start warfarin at 100microgram/Kg (max. 5mg) daily, the next day if extubated, stable and tolerating feeds. Check INR prior to starting warfarin and if greater than 1.8 discuss dosing of warfarin with the surgeons. Check INR before 2 nd dose and adjust dose accordingly. Then continue monitoring INRs daily and adjusting dose accordingly until the INR is stable. Once the INR is greater than 2, then the tinzaparin can be stopped. INR range is 2 to 3, target INR is 2.5 MVR / AVR THIS IS STANDARD TREATMENT (Any deviations from this will be decided by the surgeon and documented clearly) Start therapeutic treatment of subcutaneous tinzaparin (therapeutic) (see page 9) the morning after the operation. Antifactor Xa monitoring is required and dosage adjustment will be required as per levels (see page 9). Start warfarin at 100microgram/Kg (max. 5mg) daily, the next day if extubated, stable and tolerating feeds. Check INR prior to starting warfarin and if greater than 2 discuss dosing of warfarin with the surgeons. Check INR before 2 nd dose and adjust dose accordingly. Then continue monitoring INRs daily and adjusting dose accordingly until the INR is stable. Once the INR is greater than 2, then the tinzaparin can be stopped. MVR; INR range is 2.5 to 3.5, target INR is 3 AVR; INR range is 2 to 3, target INR is 2.5 Removal of Pacing Wires Stop heparin 6 hours prior to pacing wire removal, or stop tinzaparin 12 hours prior to pacing wire removal. Make sure the INR is equal to or less than 2.5, before the pacing wires are removed. Removal of Chest Drains If the INR is equal to or greater than 2.5, discuss with the paediatric cardiothoracic consultant. Note: The above are general guidelines only. Each patient should be treated on an individual basis in consultation with the paediatric cardiothoracic consultant. 2
Management of On X Plus (ONX) Aortic Valve Whilst on PICU follow the guidelines for MVR/AVR Once the patient returns to the paediatric cardiology ward the following pathway should be followed: The patient should already be on therapeutic tinzaparin and warfarin. Continue therapeutic tinzaparin (see page 9) until the INR is greater than 2. Once the INR is above 2, STOP the tinzaparin. Once the patient is tolerating enteral feeds, then start oral aspirin 5mg/Kg/dose daily (maximum of 75mg daily), this is life-long. Note; this is additional to warfarin treatment. The INR range for these patients is 2 to 3 for the first 90 days and then after this time it drops to 1.5 to 2.5. These patients will be discharged home on both aspirin and warfarin. Please make it clear on the warfarin clinic referral form that the INR range will need to be reduced after 90 days. 3
MEDICAL PATIENTS Anticoagulation management: Indication Blalock-Taussig Shunt / Sano Shunt/ Hybrid procedure stent Clot in the IVC/SVC/Intracardiac, extensive clots in femoral vein Femoral artery spasm following catheterisation Elective cardioversion Cardiomyopathy patient with intracardiac clots Cardiomyopathy patient with no intracardiac clots Cardiomyopathy patient with arrhythmias Kawasaki Ablation ASD device (Amplatz septal occlude, Gore device, Occlotech device) or VSD device (various) Melody valve Insertion of duct stent by cardiac catheter or right ventricular outflow tract stent Treatment Aspirin (po) 5mg/kg/dose (max. 75mg) daily (Note:post-surgery - heparin) Tinzaparin for at least 3 months starting with therapeutic heparin treatment (page 7) if necessary Start heparin at 20units/Kg/hour do not load as will have received loading dose during catheter case. Check APTT in 4hours, if greater than 85, then stop infusion and discuss with paediatric cardiologist/registrar. Discuss with cardiologist if perfusion is not improved within 4 hours, consider therapeutic treatment dose of heparin (page 7) or thrombolysis (see thrombolysis protocol and only use in conjunction with the interventional consultant responsible). Perform TOE if there is a 48 hour history or arrhythmias. If no intracardiac clots present proceed to cardioversion. If clots present anticoagulate with warfarin and cardiovert at the discretion of the cardiologist (sometimes anticoagulate for 3 months prior to procedure) INR range 2 to 3 (target INR=2.5) Start both therapeutic heparin treatment (see page 7) and warfarin at 200microgram/Kg (max. 10mg) and then monitor INR and adjust dose accordingly. Once INR is in therapeutic range, stop the heparin. Start aspirin at 5mg/kg/dose daily (max. 75mg) If warfarin required aim for INR range 2 to 3 1 month of Aspirin (po) 5mg/kg/dose (max. 75mg) daily Start Aspirin (po) 5mg/kg/dose (max. 75mg) daily for 1 week before procedure and then for 6 months after Aspirin at 5mg/kg/dose (max. 75mg) daily for at least 6 months Start heparin (prophylactic, see page 6)) at 10units/Kg/hour. Check APTT in 4hours, if greater than 85, then stop infusion and discuss with paediatric cardiologist/registrar. Overlap with Aspirin (po) 5mg/kg/dose (max. 75mg) daily for 1 day. If child is normally fully anticoagulated prior to procedure then discuss therapy with paediatric cardiologist. Occasionally full heparinisation is necessary but the interventional consultant will make a specific recommendation if this is necessary (usually when higher risk of thrombus such as competitive flows). 4
Children on Warfarin Indication MVR with INR less than 2 Treatment Start therapeutic treatment of subcutaneous tinzaparin (therapeutic) (see page 8). If the child is equal to or over 40Kg then antifactor Xa monitoring is not necessary, unless the child is in renal failure. If the child is less than 40Kg then antifactor Xa monitoring is required and dosage adjustment will be required as per levels (see page 8). Readjust dose of warfarin and reload. Check INR in 2 to 3 days AVR with INR less than 1.8 (Note if the patient has a ONX AVR, then the INR range is 1.5-2.5; in these patients if the INR is constituently below 1.5, then contact the paediatric cardiologist) Fontan circulation with INR less than 1.8 Patient with arrhythmias with INR less than 2 Readjust dose of warfarin and reload. Check INR in 3 to 4 days Readjust dose of warfarin and reload if necessary. Check INR in 7 days Readjust dose of warfarin and reload if necessary. Check INR in 7 days Cardiomyopathy patient with intracardiac clots with INR less than 2 or nil by mouth (NBM) Cardiomyopathy patient with arrhythmias with INR less than 2 if on warfarin or nil by mouth (NBM) Readjust dose of warfarin and reload. Check INR in 3 to 4 days Readjust dose of warfarin and reload. Check INR in 3 to 4 days Dental procedure Discuss management with paediatric cardiologist / dentist. Usually aim for an INR less than 2.5. Titrate the warfarin dose as appropriate for warfarin indication and dental work. Pacemaker procedure Other surgery Discuss management with implanting paediatric cardiologist. If anticoagulated for a prosthetic heart valve then aim for an INR of 2.0-2.5 without stopping warfarin Discuss management with paediatric cardiologist and surgeon. The surgeon needs to decide the acceptable INR required for surgery As a general rule, patients on warfarin for: 1. Fontan circulation - can stop warfarin for 3 days prior to surgery and then after surgery restart warfarin at patients maintenance dose once no signs of bleeding 2. AVR - can stop warfarin for 3 days prior to surgery and then after surgery restart warfarin, by giving a reload, followed by patients maintenance dose the next day, once no signs of bleeding 3. MVR- stop warfarin 3 days prior to surgery, measure INR daily. Start 5
therapeutic heparin when INR is less than 2. Give loading dose of heparin and start a continuous infusion and chase APTT according to guidelines (page 7). After surgery restart warfarin, by giving a reload, followed by patient s maintenance dose the next day, also start therapeutic subcutaneous tinzaparin (see page 8). Continue tinzaparin until the INR is 2 or above once no signs of bleeding Note; For complex congenital cardiac children with stents and shunts, these general rules may not apply and advice from the paediatric cardiologist will be required. Children on Aspirin Indication Cardiomyopathy patient with no intracardiac clots who is nil by mouth (NBM) BT shunt / conduit / Sano who is nil by mouth (NBM) Treatment Start heparin (prophylactic, see page 6)) at 10units/Kg/hour. Check APTT in 4hours, if greater than 85, then stop infusion and discuss with paediatric cardiologist/registrar Discuss management with paediatric cardiologist Definition of Intravenous Heparin for anti-coagulation Prophylactic anticoagulation of heparin: Heparin infusion to run at the rate of 10 units/kg/hour. The rate of heparin infusion does not need to be changed based on APTT level. Check clotting once daily to ensure APTT is not more than 85 secs. If APTT is greater than 85 secs, discuss with PICU Consultant, Cardiac Surgical Consultant or Paediatric Cardiologist. Therapeutic anticoagulation of heparin: Heparin infusion is used to achieve a therapeutic level for APTT (usually 60 to 85 secs). APTT should be measured 4 hours after commencing and making any changes to the infusion. Refer to therapeutic anticoagulation prescription chart for information regarding initial dose and further adjustments. 6
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Intravenous Therapeutic Heparin Dosage Guidelines Check clotting screen prior to commencing heparin (APTT, PT and INR) Loading dose 75units/kg IV over 10 minutes Maintenance dose Children less than 1 years Children equal to or greater than 1 year 28 Units/kg/hr 20units/kg/hr Check APTT 4hrs post loading dose and after each alteration in dose APTT Value ACTION APTT less than 50 Bolus of 50units/kg and increase rate by 10% APTT 50-59 Increase rate by 10% APTT 60-85 Continue at same rate, check APTT, FBC daily. Check Potassium levels alternate days APTT 86-95 Decrease rate by 10% APTT 96-120 Stop Infusion for 30 minutes. Decrease Rate by 10% APTT greater than 120 Stop heparin for 1hour Recheck APTT, if greater than 120 reduce rate by 15% and check APTT in 4hrs To Prescribe Heparin for Therapeutic indications Use the paediatric heparin prescription chart To Reverse Effect Protamine as per guidelines on page 10 8
Low Molecular Weight Heparin (LMWH) Dosing: Check coagulation screen before administration TINZAPARIN Therapeutic Treatment Dose Prophylactic Dose 0 to 2 months 275units/Kg daily * See paediatric antithrombotic guideline for dose and monitoring 2 to 12 months 250units/Kg daily * 1 to 5 years 240units/Kg daily * 5 to 10 years 200units/Kg daily * 10 to 16 years 175units/Kg daily * Dose adjustment of treatment dose of LMWH Anti-Xa level (units/ml) Dose change (%) 0.1-0.3 + 20 0.3-0.5 + 10 0.5-1.0 0 1.0-1.3-10 1.3-1.6-20 * See paediatric antithrombotic guideline for dose and monitoring (on Leeds health pathways) To Reverse Effects Protamine as per guidelines on page 10 Low molecular weight heparins in renal impairment and liver impairment. The use of unfractionated heparin may be a preferable option in renal or liver dysfunction. If low molecular weight heparin is used consider reducing dose, increasing the frequency of monitoring anti-xa levels and adjusting dose accordingly. Patients with a creatinine clearance of less than 30mL/min should receive an initial 50% dose reduction. The anti-xa level should be measured after the first dose, further monitoring and dose modifications should follow the suggested guidance. 9
Reversal of Heparin with Protamine Heparin Protamine Dose Time since last dose (min) < 30 1 mg per 100units heparin received 30-60 0.5-0.75 mg per 100units heparin received 60-120 0.375-0.5 mg per 100units heparin received >120 0.25-0.375 mg per 100units heparin received Maximum Dose 50mg Infusion Rate 10mg/mL, Solution should not exceed 5mg/min Treatment of Warfarin induced bleeding Major Bleeding (Limb or Life Threatening) 1. Stop Warfarin 2. Give Phytomenadione (Vitamin K1) by slow IV injection 0 to 12 years old: 50 to 100 micrograms/kg Over 12 years old: 5 to 10 mg 3. Give Prothrombin Complex Concentrate (PCC) (Factors II, VII, X) 25units/Kg or if not available Fresh Frozen Plasma (FFP) 15mL/Kg 4. Exclude local cause of bleeding INR greater than 8 no bleeding or minor bleeding 1. Stop Warfarin, restart when INR is less than 5 2. If other risk factors for bleeding exist In patients with prosthetic Mitral or Aortic Valve consider FFP at 15mL/Kg In patients with Fontan circulation, other reasons for anticoagulation consider low dose Phytomenadione (Vitamin K1) 0 to 12 years: 5 to 10 microgram/ Kg by slow intravenous injection or 50 to 100 microgram/kg orally. Repeat dose if INR remains high after 24 hours Over 12 yrs: 500 micrograms by slow intravenous injection or 5mg orally. Repeat dose if INR remains high after 24 hours INR 6 to 8, no bleeding or minor bleeding Stop Warfarin, restart when INR is less than 5 INR is greater than 6 Reduce dose, restart warfarin when INR is less than 5 Unexpected bleeding at therapeutic levels Assess for local/ systemic cause of blood loss 10
References These Guidelines were written according to current practice and the following references: 1. Andrew M, Marzinotto K, Massicote P et al. Heparin Therapy in Paediatric Patients: A prospective cohort study Paediatric Research 1994; 35(1):78-83 2. Baglin T, Barrowcliffe TW, Cohen A et al. Guidelines for use and monitoring of Heparin British Society of Haematology 2006; 133 : 19-34 3. Dix D, Andrew M, Marizotto V et al. The use of low molecular weight heparin in paediatric patients: a prospective cohort study. Journal of Paediatrics 2000; 135: 439-445 4. Maricotte P, Adams M, Marzinotto V et al. Low Molecular Weight Heparin in Paediatric Patients with thrombotic disease: a dose finding study. Journal of Paediatrics 1996, 128:313-318 5. Monagle P, Cochrane A, McCrindle B et al Thromboembolic complications after Fontan procedures- the role of prophylactic anticoagulation J Thorax Cardiovascular Surgery 1998, 115: 493-498 6. Reller MD Congenital Heart Disease: Current Indications for Antithrombotic Therapy in Paediatric Patients Current Cardiology Reports 2001; 3:90-95 7. Richards M, Brooks T et al Protocol of use of anti-thrombotic treatment in children Leeds University Hospital Trust Guidelines 2007 8. Monagle P, Chan A et al. Antithrombotic therapy in neonates and children: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of Chest Physicians evidence- based clinical practice guidelines Chest 2012; 141(2):e737s-e801s 9. Guidelines on oral anticoagulant with warfarin, Fourth Edition, 2011. British Journal of Haematology. 2011; 154: 311-324 Written by: Teresa Brooks (Advanced Clinical Pharmacist for Paediatric Cardiology) Approved by: Paediatric Cardiology Clinical Governance Written: February 2014 Review date; October 2021 Last updated: October 2018 11