Anticoagulation Management - | Health
Canberra Hospital and Health ServicesClinical ProcedureAnticoagulation Management – Adult Contents TOC \h \z \t "Heading 1,1,Heading 2,2" Contents PAGEREF _Toc422921873 \h 1Purpose PAGEREF _Toc422921874 \h 2Alerts PAGEREF _Toc422921875 \h 2Scope PAGEREF _Toc422921876 \h 2Section 1 – Anticoagulation Decisions PAGEREF _Toc422921877 \h 2Section 2 – Initiation and Management of Heparin PAGEREF _Toc422921878 \h 5Section 3 – Initiation and Management of Warfarin PAGEREF _Toc422921879 \h 8Section 4 – Initiation and Management of Low Molecular Weight Heparin (LMWH) PAGEREF _Toc422921880 \h 12Section 5 – Initiation and Management of Direct Acting Oral Anticoagulants/New Oral Anticoagulants PAGEREF _Toc422921881 \h 14Section 6 – Perioperative Management of Anticoagulation PAGEREF _Toc422921882 \h 20Section 7 – Management of Bleeding in Anticoagulated Patients PAGEREF _Toc422921883 \h 21Section 8 – Diagnosis and Management of Heparin Induced Thrombocytopenia (HIT) PAGEREF _Toc422921884 \h 22Section 9 – Anticoagulation in Pregnancy PAGEREF _Toc422921885 \h 25Implementation PAGEREF _Toc422921886 \h 27References PAGEREF _Toc422921887 \h 27Abbreviations PAGEREF _Toc422921888 \h 28Search Terms PAGEREF _Toc422921889 \h 28Attachments PAGEREF _Toc422921890 \h 28Attachment 1 – Perioperative Anticoagulation Guidelines PAGEREF _Toc422921891 \h 29PurposeThe purpose of this procedure is to:provide guidance to clinicians on the appropriate use of anticoagulants specify procedures to be followed to identify patients in need of anticoagulationspecify procedures for initiating, monitoring and managing anticoagulation in people being cared for under the direction of ACT Health.ScopeAlertsAnticoagulant medications have been repeatedly identified as causes for serious complications. Although some incidents are expected due to the nature of these medications predisposing to bleeding, failure to follow appropriate prescribing and monitoring procedures can lead to serious bleeding or thrombotic incidents.Special consideration should be given to those patients, on anticoagulant medications, that have an epidural in place or are at risk of a fall. ScopeThe procedure will be applied to all patients admitted to Canberra Hospital. It describes the procedures to be undertaken by medical officers when considering the prescription of anticoagulation medications, when monitoring and managing people on anticoagulation medications and when managing the perioperative or bleeding patient on anticoagulant medications through Canberra Hospital and Health Services. For information on Venous Thromboembolism (VTE) Prevention, see the Venous Thromboembolism (VTE) Prevention Procedure.Out of scope:Patients less than 16 years.Section 1 – Anticoagulation DecisionsProcedure When deciding to use anticoagulation medications for a patient, the medical officer is responsible for: determining the indicationevaluating the risk of treatmentdocumenting both in the medical record. The decision to prescribe should be based on an assessment of risk. The use of risk stratification tools in atrial fibrillation (AF), such as the CHADS2PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SaWV0YnJvY2s8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFy
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ADDIN EN.CITE.DATA 1,2 score, is strongly encouraged.Decisions regarding anticoagulation should be made in conjunction with the patient, being mindful of patient preferences in addition to the medical indications and contraindications. Where there is a strong indication for anticoagulation (eg acute VTE, high risk AF) but a decision is made to withhold anticoagulation, this should also be adequately documented. Table 1 (below) may be used to guide anticoagulation choices. Further information is available under specific parts of this document and within prescribing information.Table SEQ Table \* ARABIC 1 - Anticoagulation ChoicesDrugMechanism of actionReversibilityMain indicationsContraindicationsMonitoringHeparinIndirect inhibitor of FXa and thrombin via antithrombinYes.Short half life. Ceasing infusion usually adequate. Protamine may be used.Short term anticoagulation where there is a need for the ability to cease quickly (High bleeding risk / perioperative)Extracorporeal and procedural anticoagulationVTE prophylaxisHeparin induced thrombocytopenia (HIT)APTTLow molecular weight heparin Indirect inhibitor of FXa via antithrombinPartially reversible with Protamine.Initiation of anticoagulationVTE prophylaxisVTE treatment in patients with active malignancyHeparin induced thrombocytopenia (HIT)Not recommended in severe renal failureDose reduction required in moderate renal impairmentUsually not required.Consider specific anti-Xa levels in renal impairment and morbid obesityDanaparoidIndirect inhibitor of FXa via antithrombinCease infusion (elimination half life 10 hours)Heparin Induced Thrombocytopenia (HIT)Caution in renal impairment. Has a long half life – 24 hoursAnti-Xa levelsWarfarinInhibition of production of vitamin K dependent clotting factors prothrombin, FVII, FIX, FXPhytomenadione, prothrombin complex concentrateLong term anticoagulation is preferred where there is renal impairment or issues with compliance.PregnancyINRRivaroxabanDirect inhibition of FXaNoTreatment and prevention of VTEStroke prophylaxis in non-valvular AFPregnancyRenal impairment (CrCl estimated by Cockcroft Gault equation <30mL/min)Liver disease (Childs-Pugh >A)Usually not requiredSpecific anti-Xa levels availableApixabanDirect inhibition of FXaNoTreatment and prevention of VTEStroke prophylaxis in non-valvular AFPregnancyRenal impairment (CrCl estimated by Cockcroft Gault equation <25mL/min)Liver disease (Childs-Pugh >A)Usually not required.Specific anti-Xa levels available.DabigatranDirect inhibition of thrombinNoTreatment and prevention of VTEStroke prophylaxis in non-valvular AFPregnancyRenal impairment (CrCl estimated by Cockcroft Gault equation <30mL/min)Liver disease with coagulopathyUsually not required.Dilute thrombin time available. Consider in renal impairment with CrCl estimated 30-40mL/minSection 2 – Initiation and Management of HeparinProcedureIndicationTherapeutic anticoagulation where there is a concern regarding potential for bleedingTreatment of acute venous thromboembolism in the medically unstable patient or in those patients whom surgery is imminentPrevention of arterial thromboembolism in medically unstable patients with cardiac arrhythmias and/or presumed embolic strokePerioperative anticoagulation in patients with prosthetic heart valvesContraindicationsNot be administered via the intramuscular route Known hypersensitivity to heparin, including heparin induced thrombotic thrombocytopeniaSevere thrombocytopeniaPatients for whom suitable blood coagulation tests cannot be performed at appropriate intervalsPatients who are in an uncontrollable active bleeding statePrecautionsGastric or duodenal ulcers, continuous tube drainage of the stomach or small intestineSubacute bacterial endocarditisSevere hypertensionDuring and immediately after spinal tap or anaesthesia, major surgery especially eye, brain or spinal cordIncreased bleeding tendency e.g. haemophiliaLiver disease, renal diseasePresentationHeparin pre-mix bag: 25,000 units in 250mL sodium chloride 0.9% (concentration 100 units/mL)Location StoredImprest locations and Main Pharmacy PrescribingIt is the responsibility of the prescriber to check the baseline PT, APTT and FBC and to seek senior advice if abnormal.The patient’s weight must be ascertained either by physically weighing, or if not possible, by accurate estimation.Assess each patient for risk factors associated with bleeding complications from anticoagulant therapy. Table 3 outlines some risk factors for bleeding complications. Seek guidance if unsure.The prescriber is responsible for ordering the IV heparin infusion, and reviewing and rewriting the order daily. The order is to be written on the Intravenous Fluid and Additives Order Chart. The rate of the infusion is to be specified in units/kg/hr as well as the corresponding mL/hr rate on the Anticoagulation Therapy Record Form.If anticoagulation with heparin needs to be discontinued for clinical reasons, it is the responsibility of the prescriber to ensure the order is ceased.PreparationUse heparin standard bag: 25,000 units in 250mL sodium chloride 0.9%.Line RequirementsPatients will require a dedicated line for heparin infusions. The infusion MUST NOT be stopped or interrupted for other medications.APTT blood samples should be drawn from the contra-lateral arm if possible, or if a double- lumen line, from the lumen that does not have heparin running.AdministrationTable SEQ Table \* ARABIC 2 - Heparin AdministrationLoading DoseContinuous InfusionDoseThe loading dose may be omitted in patients considered at increased risk for bleeding.60-80kg: 5,000 units<60kg or >80kg: 80 units/kg60-80kg: After loading dose, commence IV infusion , using 25,000 unit /250mL premix bag, at a rate of 12.5mL/hr (1250 units/hr)<60kg or >80kg: Commence infusion at a rate of 18 units/kg/hr (0.18mL/kg/hr)Adjust dose according to APTT referring to nomogram provided by Pathology with Coagulation Profile.PreparationUse heparin standard bag:25,000 units in 250mL sodium chloride 0.9%60-80kg: Administer 5000 units loading dose(5,000 units = 50mL)<60kg or >80kg: Calculate dose individually as per above (80units/kg = 0.8mL/kg)Use heparin standard bag:25,000 units in 250mL sodium chloride 0.9%Infusion PumpSettings60-80kg: Set pump to administer50 mL over 5 minutes = 600mL/hr<60kg or >80kg: Calculate dose as per above(80units/kg over 5 minutes)60-80kg: Once loading dose administered, reset pump to administer 12.5mL /hr<60kg or >80kg: Calculate rate as per above (0.18mL/kg/hr)AdministrationTimeOver 5 minutesContinuous infusion commencedat rate of 12.5mL/hr (for standard weight range only) or as calculated and adjusted according to APTTTitration RequiredAdjust the dose according to APTT referring to nomogram provided by Pathology with Coagulation Profile.Results will differ according to the reagent used by Pathology, ranges and nomogram may be varied if reagents change.IncompatibilitiesComplex: refer to the Australian Injectable Drugs Handbook2 for a complete up-to-date list or contact your ward pharmacist.Therapeutic Drug MonitoringCheck APTT 6 hours after commencing infusion, and then as recommended by nomogram, according to APTT.Adjust the dose according to APTT referring to nomogram provided with the coagulation profile pathology report.Once in the therapeutic range, APTT should be checked daily as the clinical effect may change depending on antithrombin target and protein binding.Check platelet count three times weekly, if there is an abrupt decrease in platelet count, (e.g. 50%) consider Heparin Induced Thrombocytopenia (HIT) and arrange immediate Haematology consult.If APTT ratio is not in the therapeutic range after three consecutive measurements seek Haematology consult.In certain clinical circumstances an APTT may be inaccurate; and alternative is an anti Xa assay.A Haematology consult is recommended if APTT prior to anticoagulation is prolonged or if there are any concerns.Adverse EffectsBleedingThe major adverse event potentially related to standard heparin infusion is bleeding. If a patient on heparin develops bleeding, cease heparin infusion and seek urgent Haematology consult.Heparin Induced Thrombocytopenia with Thrombosis (HIT).Local irritation.Hypersensitivity reactions.Changing Therapy to or from Therapeutic EnoxaparinHeparin Infusion to EnoxaparinIf the patient is to be changed from a heparin infusion to enoxaparin, the calculated dose of enoxaparin should usually be administered as soon as the heparin infusion is ceased, assuming the patient is not over-anticoagulated on heparin at the time.Enoxaparin to Heparin InfusionIf the patient is to be changed from subcutaneous enoxaparin to a heparin infusion, the heparin infusion should normally be commenced when the next dose of enoxaparin is due, assuming the patient is not over-anticoagulated at the time.If there is uncertainty as to the patient’s coagulation status and/or the patient is over- anticoagulated, haematology should be consulted before the change occurs.Care should be taken to ensure that it is clear which anticoagulant is being ceased, and that the plan for changing from one anticoagulant to the other is communicated to clinical staff to avoid duplication of anticoagulant therapy.Back to Table of Contents Section 3 – Initiation and Management of WarfarinProcedure Warfarin should be prescribed in the designated area of the Inpatient Medication Chart. 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ADDIN EN.CITE.DATA 3Risk FactorDetailsAge >65 years Cardiac Uncontrolled hypertension Gastrointestinal History of gastrointestinal haemorrhage, active peptic ulcer, significant liver dysfunction or liver failure Haematologic/ Oncologic Thrombocytopenia (Platelet count < 50x109/L), platelet dysfunction, coagulation defect, underlying malignancy Neurologic History of stroke, cognitive or psychological impairment Renal Renal insufficiency Trauma Recent trauma, history of falls, major surgery less than 10-14 days ago Alcohol/impaired nutritional status Excessive alcohol intake, hypoalbuminaemia Medications Refer to potential interactions Determining the INR RangeDetermine & document on the medication chart the target INR range for the patient. Table 4 (below) can be used as a guide for standard indications. Table SEQ Table \* ARABIC 4 - Target INRs for Common Warfarin Indications ADDIN EN.CITE <EndNote><Cite><Author>Tran</Author><Year>2013</Year><RecNum>222</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>222</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">222</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tran, H. A.</author><author>Chunilal, S. D.</author><author>Harper, P. L.</author><author>Tran, H.</author><author>Wood, E. M.</author><author>Gallus, A. S.</author></authors></contributors><auth-address>Clinical Haematology, The Alfred Hospital, Melbourne, VIC. huyen.tran@monash.edu</auth-address><titles><title>An update of consensus guidelines for warfarin reversal</title><secondary-title>Med J Aust</secondary-title></titles><periodical><full-title>Med J Aust</full-title></periodical><pages>198-9</pages><volume>198</volume><number>4</number><edition>2013/03/05</edition><keywords><keyword>Administration, Oral</keyword><keyword>Anticoagulants/ administration & dosage</keyword><keyword>Antifibrinolytic Agents/therapeutic use</keyword><keyword>Blood Coagulation Factors/therapeutic use</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Drug Administration Schedule</keyword><keyword>Drug Monitoring/standards</keyword><keyword>Hemorrhage/chemically induced/ prevention & control</keyword><keyword>Humans</keyword><keyword>International Normalized Ratio/standards</keyword><keyword>Plasma</keyword><keyword>Postoperative Care</keyword><keyword>Surgical Procedures, Operative</keyword><keyword>Vitamin K 1/therapeutic use</keyword><keyword>Warfarin/ administration & dosage</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar 4</date></pub-dates></dates><isbn>1326-5377 (Electronic)
0025-729X (Linking)</isbn><accession-num>23451962</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>4Target INR Indication for warfarin 2-3 Prevention of DVTtherapy for DVT or PEprevention of systemic embolism (AF, valvular heart disease, after AMI, tissue heart valves - 1st three months) 2.5-3.5 Bi-leaflet mechanical heart valve (aortic)3-4.5 Mechanical prosthetic heart valve (high risk), and high risk conditions such as Antiphospholipid Syndrome. Initiating Warfarin Therapy Acute DVT or PE: Treatment with Low molecular weight heparin (LMWH) or unfractionated heparin should overlap with warfarin. Commence warfarin on the same day as the heparin. Heparin should be given for a minimum of 5 days ensuring the INR is in the therapeutic range for > 2 consecutive days before the heparin is ceased. Post-operative patients: Restart with ‘normal’ pre-operative maintenance dose. Some patients may require overlap with heparin therapy. This will need to be assessed for each individual. Seek specialist advice if unsure. Table SEQ Table \* ARABIC 5 - Typical Daily Dose of Warfarin to Maintain INR 2 - 3Age (years) Warfarin daily dose < 50 6 – 8mg 50 – 69 4 – 6mg >70 3mg NOTE: The practice of giving warfarin 10mg on days 1 & 2 (i.e. Loading doses) are not recommended as it does not result in more rapid anticoagulation and is more likely to result in poor control of INR.Adjustment of Warfarin Doses Table 6 (below) can be used to guide dose adjustment.Table SEQ Table \* ARABIC 6 – Warfarin Dose Adjustment Guide for Target INR 2 - 3 ADDIN EN.CITE <EndNote><Cite><Author>Gallus</Author><Year>2000</Year><RecNum>246</RecNum><DisplayText><style face="superscript">5</style></DisplayText><record><rec-number>246</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">246</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gallus, A. S.</author><author>Baker, R. I.</author><author>Chong, B. H.</author><author>Ockelford, P. A.</author><author>Street, A. M.</author></authors></contributors><auth-address>Australasian Society of Thrombosis and Haemostasis, Perth, WA.</auth-address><titles><title>Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis</title><secondary-title>Med J Aust</secondary-title></titles><periodical><full-title>Med J Aust</full-title></periodical><pages>600-5</pages><volume>172</volume><number>12</number><edition>2000/07/29</edition><keywords><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Anticoagulants/adverse effects/ therapeutic use</keyword><keyword>Atrial Fibrillation/complications</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Stroke/prevention & control</keyword><keyword>Thrombosis/drug therapy/prevention & control</keyword><keyword>Warfarin/adverse effects/ therapeutic use</keyword></keywords><dates><year>2000</year><pub-dates><date>Jun 19</date></pub-dates></dates><isbn>0025-729X (Print)
0025-729X (Linking)</isbn><accession-num>10914107</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>5INR Recommended Action for warfarin management < 1.5 Increase dose by 30-40% (usually 2mg) Repeat INR 1.6 – 1.9 Consider increasing warfarin dose by 20-25% (usually about 1mg/day) if 2 consecutive INRs are low 2 – 3No change 3.1 – 4.5 Seek advice from senior medical officer Repeat INR 4.6 - 5 Omit warfarin for one night Repeat INR > 5Refer to the section ‘Management of an elevated INR’ in this document INR Monitoring During the induction/initiation phase monitor the INR every daily if on therapeutic heparin.Note that the full effect of a dose change is not reflected in the INR for 2-3 days.Maintenance therapy: Once the INR is stable and in the therapeutic range, INRs can be measured weekly. The interval can then be gradually increased at the prescriber’s discretion up to every 4 weeks. More frequent INR monitoring will be required if there are significant diet changes, intercurrent illness or other medication changes have been made.Medication Interactions Many medicines interact with warfarin. The effects can be unpredictable. Any change in medications suspected to interact with warfarin will require close monitoring of the patient’s INR. There are a number of tools available to assist with checking for potential interactions, including Lexicomp available through the ACT Health Library. If unsure, please phone the medicines information team at the Canberra Hospital (6244 - 3333) or contact the ward pharmacist (6244 - 2532) for advice. Patient Education All staff involved with patient care should discuss the therapy with the patient or other care providers where possible. This should include but is not limited to; reason for prescribing, importance of INR monitoring, target INR range, side effects and the importance of adhering to dose recommendations. There is a consumer information booklet available as a separate resource that is routinely provided to patients. The National Inpatient Medication Chart (NIMC) contains a warfarin education check box. This is the national standard for communication between health professionals that education has been provided. This tick box is audited for the purpose of accreditation and should be annotated by staff once education has been provided.Management of Bleeding or an Excessively Elevated INRFor non-bleeding patients, specific reversal is often not required, but may be indicated in patients at high risk of bleeding.For bleeding patients, general measures should be undertaken as outlined in Section 7.Warfarin may be reversed with immediate infusion of prothrombin complex concentrate (PCC) available from the transfusion laboratory. This is a three factor product (containing prothrombin, FIX and FX). Although it contains no FVII, observational studies report superiority over reversal with FFP alone. FVII has a short half life and there are limited amounts of clotting factors within each unit of FFP. National Guidelines recommend the addition of FFP to Prothrombinex only for life threatening haemorrhage.In all cases where warfarin reversal is required, phytomenadione should be administered, to restore the production of coagulation factors. Table 7 (below) provides guidance on warfarin reversal in these circumstances. (Adapted from Tran et al, 2013 ADDIN EN.CITE <EndNote><Cite><Author>Tran</Author><Year>2013</Year><RecNum>222</RecNum><DisplayText><style face="superscript">4</style></DisplayText><record><rec-number>222</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">222</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Tran, H. A.</author><author>Chunilal, S. D.</author><author>Harper, P. L.</author><author>Tran, H.</author><author>Wood, E. M.</author><author>Gallus, A. S.</author></authors></contributors><auth-address>Clinical Haematology, The Alfred Hospital, Melbourne, VIC. huyen.tran@monash.edu</auth-address><titles><title>An update of consensus guidelines for warfarin reversal</title><secondary-title>Med J Aust</secondary-title></titles><periodical><full-title>Med J Aust</full-title></periodical><pages>198-9</pages><volume>198</volume><number>4</number><edition>2013/03/05</edition><keywords><keyword>Administration, Oral</keyword><keyword>Anticoagulants/ administration & dosage</keyword><keyword>Antifibrinolytic Agents/therapeutic use</keyword><keyword>Blood Coagulation Factors/therapeutic use</keyword><keyword>Dose-Response Relationship, Drug</keyword><keyword>Drug Administration Schedule</keyword><keyword>Drug Monitoring/standards</keyword><keyword>Hemorrhage/chemically induced/ prevention & control</keyword><keyword>Humans</keyword><keyword>International Normalized Ratio/standards</keyword><keyword>Plasma</keyword><keyword>Postoperative Care</keyword><keyword>Surgical Procedures, Operative</keyword><keyword>Vitamin K 1/therapeutic use</keyword><keyword>Warfarin/ administration & dosage</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar 4</date></pub-dates></dates><isbn>1326-5377 (Electronic)
0025-729X (Linking)</isbn><accession-num>23451962</accession-num><urls></urls><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>4)Table SEQ Table \* ARABIC 7 - Guidelines for Warfarin ReversalClinical ScenarioINRPhytomenadione doseFFP / CSU / ELPPTXOther ActionNext INRNo bleeding, recent or urgent surgery<4.5NoneNoneNoneConsider ceasing or reducing the dose of warfarin4.5-100.5mg - 1mg IV or 1mg - 2mg PO if high risk of bleedingNoneNoneWithhold warfarinWithin 24 hours>103mg - 5mg PO or IVNone15-30units/kg if bleeding risk is high or urgent surgery is requiredWithhold warfarin12-24 hoursClinically significant bleeding where warfarin induced coagulopathy is considered a significant contributor>1.5 with critical organ (life-threatening) bleeding5 - 10mg IV1-2 units15- 50units/kgWithhold warfarin. Assess continuously until INR<5 and bleeding stops15 minutes after correction>2, with not life-threatening bleeding5 - 10mg IVNone15-50units/kgCease warfarin15 minutes after correction Discharge Planning and Ongoing Care Warfarin dosing information will be required for handover on discharge. On discharge, the patient’s GP will need to receive copies of INR results and all relevant details of treatment during the initiation phase. If this is not possible, seek assistance from the hospital GP Liaison Office. Prescribers are responsible for ensuring that INR monitoring can be performed 1-2 days following discharge and/or patients will have an appointment with their GP in the next 1- 2 days if discharging a patient who has not yet established a therapeutic INR range. If the patient requires a referral to Community Nursing or HITH (Hospital in the Home), information on INR results during the admission as well as instructions regarding warfarin dosing and management details will be required. If the patient is not self medicating, medication orders will be required. Prescribers providing Rule 3 Exemption Pathology Forms for multiple INRs must personally take on the responsibility for responding to all INRs resulting from that form.Back to Table of Contents Section 4 – Initiation and Management of Low Molecular Weight Heparin (LMWH)Procedure Prior to Initiation of LMWHCheck baseline creatinine clearance, APTT, PT and platelet count.Consider the risk of bleeding. The risk of bleeding needs to be weighed against the risk of thromboembolic events. Table 8 (below) may be used as a guide.Check the patient’s weight. This should be measured, although an estimate may need to be used in the acute situation if weighing is not practical. If an estimate is used, it should be clearly documented that the dose is based on an estimate. Initiating LMWHEnoxaparin is the preferred LMWH on the CHHS Formulary.Determine the dose and dosing schedule. For adults, Table 8 summarises standard dosing. For treatment in children, seek specialist advice. LMWH clearance may be increased in children.Chart LMWH on the NIMS Chart, preferably in the VTE prophylaxis section of the chart.LMWH should be administered prior to warfarin, when they are being commenced concurrently. Table SEQ Table \* ARABIC 8 - Enoxaparin DosingDosing IntentionNormal doseSevere renal impairment (CrCl<30mls/min)*Extreme weight ranges#(<50kg or BMI> 40kg/m2)Prophylaxis40mg SUBCUT daily20mg SUBCUT dailyConsider 0.5mg/kg SUBCUT twice dailyTherapeutic dosing1mg/kg SUBCUT twice or1.5mg/kg SUBCUT daily1mg/kg SUBCUT daily1mg/kg SUBCUT twice or1.5mg/kg SUBCUT daily.For high BMI, dose reduction may be required based on measured anti-Xa levels, aiming for a 4 hour post dose level of 0.5-1units/mL (twice daily dosing) or 0.5-1.5units/mL for daily dosing.* For use in haemodialysis and other extracorporeal procedures, see specific procedural policies.# There is no consensus for dose adjustment at the extremes of weight. LMWH levels are higher in low weight individuals treated with fixed dose prophylaxis regimens. In morbidly obese patients fixed dosing may lead to lower levels. However, in this group weight based treatment dosing may lead to higher concentrations due to relatively reduced volumes of distribution. MonitoringThere is no need for routine monitoring of LMWH levels in the majority of patients.Monitoring may be required in renal impairment, or obese patients.Heparin induced thrombosis-thrombocytopenia syndrome (HITTS) is rare with LMWH, however may occur, particularly if there has been recent exposure to unfractionated heparin. A platelet count 7-10 days after initiation of therapy is recommended.Patient education and training on self-administration must be provided when patients are to remain on therapy beyond the duration of the current admission/attendance.While no specific LMWH monitoring is required by patients’ general practitioners, handover to the GP must include the indication for therapy, expected duration of treatment and any specific follow up arrangements for anticoagulation.Back to Table of Contents Section 5 – Initiation and Management of Direct Acting Oral Anticoagulants Direct acting Oral Anticoagulants are a group of small molecule drugs that directly inhibit enzymatic activity of coagulation factors.Procedure Prior to Commencing Direct acting Oral Anticoagulants Baseline FBC, PT and APTT should be performed and investigated if abnormal. A pregnancy test is recommended in women of childbearing age as Direct acting Oral Anticoagulants are contraindicated in pregnancy.Patient age and weight should be determined.Creatinine clearance should be calculated using the COCKCROFT-GAULT equation. Cockcroft Gault equation: estimated CrCl = (140-age in years) x mass (in kg) x 1.23 (x 0.85 for females)/serum creatinine (micromol/L).Assess patient’s indication and suitability, including bleeding risk and concurrent medications for potential drug interactions. Table 3 may be used as a guide to assess the risk of bleeding.Doses and Duration of TreatmentTable 9 (below) summarises the doses and duration of treatment with Direct acting Oral Anticoagulants.Table SEQ Table \* ARABIC 9 - Doses and Duration of TreatmentPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NSU1TPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 6,7 with Direct acting Oral AnticoagulantsIndicationDabigatran (Pradaxa)Rivaroxaban (Xarelto)Apixaban (Eliquis)Stroke prevention in non-valvular AF with ≥ 1 risk factor150mg twice daily indefinitely110mg twice daily for ages ≥ 75years, CrCl 30-50mL/min, high bleeding risk20mg daily indefinitely15mg daily if CrCl 30-50mL/min5mg twice daily indefinitely2.5mg twice daily if two of these risk factors:Age ≥ 80 yearsWeight ≤ 60kgCreatinine ≥ 133 mmol/LTreatment of DVT150mg twice daily for 3 months (with parenteral anticoagulant for at least 5 days prior to starting dabigatran110mg twice daily for ages ≥ 75years, CrCl 30-50mL/min, high bleeding risk 15mg twice daily for 3 weeks then 20mg once daily10?mg twice daily for 7?days, then 5?mg twice dailyReduce dose after 6?months to that for prevention of subsequent VTE if long-term treatment is needed.Prevention of recurrent DVT and / or PE150mg twice daily 110mg twice daily for ages ≥ 75years, CrCl 30-50mL/min, high bleeding risk 15mg twice daily for 3 weeks then 20mg once daily20mg once daily2.5mg twice dailySpecial ConsiderationsTable 10 outlines the special considerations in use of Direct acting Oral Anticoagulants.Table SEQ Table \* ARABIC 10 - Special Considerations for use of Direct acting Oral AnticoagulantsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UcmFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 8. These patients may be considered for a lower dose or alternative agent. Measurement of therapeutic levels may be used to guide dosing in this group of patients. When measurement is considered necessary, haematological advice is recommended. The following assays are recommended:Dabigatran – Thrombin time (TT) is sensitive to even small concentrations. Normal results indicate the absence of dabigatran. When there is a need to determine therapeutic levels, a dilute thrombin time (HEMOCLOT ?) is recommended.Rivaroxaban and apixaban – Specific anti-Xa assays are used to determine therapeutic levels. The specific Xa inhibitor should be specified on the request form as different assays are performed.The recommendations for monitoring Direct acting Oral Anticoagulants are summarised in Table 11.Table SEQ Table \* ARABIC 11 - Summary of Laboratory Tests and Patterns for Direct acting Oral AnticoagulantsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UcmFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 7,9TestDabigatranRivaroxabanApixabanSignificant anticoagulant effect unlikelyTT and APPT normalPT normalNormal PT does not exclude presence of therapeutic apixabanAnticoagulant effect presentTT prolongedAPTT prolongedPT prolonged or normalPT prolonged or normalSpecific assays to quantify drug presenceDilute thrombin clotting time assay (HEMOCLOT? assay)Modified anti Xa specific for rivaroxabanModified anti Xa specific for apixabanDirect acting Oral Anticoagulants may interfere with specialised coagulation assays, including factor levels, natural anticoagulant levels (protein C, S and antithrombin) and lupus anticoagulant. Bleeding RiskAll anticoagulants carry a risk of bleeding. There are some differences between oral anticoagulants and bleeding risk which may be considered when prescribing. These are summarised in Table 12.Table SEQ Table \* ARABIC 12 - Comparison of Bleeding Risk between Warfarin and Direct acting Oral Anticoagulants DrugWarfarinDabigatranRivaroxabanApixabanBleeding RiskRisk highest in the first 3 months of starting treatmentCompared with warfarin:Slightly lower risk of bleeding in the brainSlightly higher risk of bleeding in the gutCompared with warfarin:Slightly lower risk of bleeding in the brainSlightly higher risk of bleeding in the gutCompared with warfarin:Slightly lower risk of bleeding in the brainNo difference in bleeding risk in the gutTransitioning Between AnticoagulantsTransition between anticoagulants should be done by a senior medical officer or in consultation with a Haematologist. Conversion with Parenteral AnticoagulantsTable 13 (below) summarises the Conversion with Parenteral Anticoagulants.Table SEQ Table \* ARABIC 13 - Conversion with Parenteral Anticoagulants ADDIN EN.CITE <EndNote><Cite><Author>District</Author><Year>2014</Year><RecNum>225</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>225</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">225</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>Sydney Local Health District</author></authors><secondary-authors><author>Health</author></secondary-authors></contributors><titles><title>Anticoagulation Guideline</title></titles><dates><year>2014</year></dates><pub-location>Sydney</pub-location><publisher>NSW Health</publisher><urls></urls></record></Cite></EndNote>9From LMWH to Direct Oral AnticoagulantsStart Direct acting Oral Anticoagulants when next LMWH dose dueFrom continuous IV heparin infusion to Direct acting Oral AnticoagulantsCommence Direct acting Oral Anticoagulants immediately when infusion is ceasedFrom LMWH to Direct acting Oral AnticoagulantsCommence Direct acting Oral Anticoagulants when the next LMWH dose would have been due (12-24 hours after the final LMWH dose)From rivaroxaban or apixaban to UFH or LMWHStart UFH or LMWH 12-24 hours after the last dose (1-2 half lives of the Direct acting Oral Anticoagulants) No bolus dose of UFH is required.From dabigatran to UFH or LMWHCrCl ≥ 30mL/min: wait 12- 24 hours orCrCl ≤ 30mL/min: wait 48hours, after last dose of dabigatran before starting UFH or LMWH.Conversion with WarfarinWarfarin to Direct acting Oral AnticoagulantsPatients stably anticoagulated on warfarin do not necessarily need to change treatment, especially if their anticoagulation has been stable. If patients choose to transition to a Direct acting Oral Anticoagulants, discontinue warfarin:Measure INR. If the INR is < 2, commence Direct acting Oral Anticoagulants the day after warfarin is ceased.If the INR is >2.3 then measure INR in 1-2 days and commence Direct acting Oral Anticoagulants when <2.Direct acting Oral Anticoagulants to Warfarin ADDIN EN.CITE <EndNote><Cite><Author>District</Author><Year>2014</Year><RecNum>225</RecNum><DisplayText><style face="superscript">9</style></DisplayText><record><rec-number>225</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">225</key></foreign-keys><ref-type name="Government Document">46</ref-type><contributors><authors><author>Sydney Local Health District</author></authors><secondary-authors><author>Health</author></secondary-authors></contributors><titles><title>Anticoagulation Guideline</title></titles><dates><year>2014</year></dates><pub-location>Sydney</pub-location><publisher>NSW Health</publisher><urls></urls></record></Cite></EndNote>9When switching from Direct acting Oral Anticoagulants to warfarin, it is necessary to take into account:The elimination half life of the Direct acting Oral Anticoagulant which will be affected by the patient’s renal functionDelay in onset of action of warfarinINR reading which is affected by both Direct acting Oral Anticoagulants and warfarin. If maintaining anticoagulation is critical, switching from Direct acting Oral Anticoagulants to enoxaparin may be preferable.Table SEQ Table \* ARABIC 14 - Suggested Conversion StrategiesCreatinine ClearanceRivaroxaban or ApixabanDabigatranGreater than 50mL/minStop rivaroxaban or apixaban 4 days after starting warfarinStop dabigatran 3 days after starting warfarin31-50mL/minStop rivaroxaban or apixaban 3 days after starting warfarinStop dabigatran 2 days after stating warfarin15-30mL/minStop rivaroxaban or apixaban 2 days after starting warfarinStop dabigatran 1 dayafter starting warfarinLess than 15mL/minConsult HaematologistConsult HaematologistStart with a warfarin dose of 5mg or lessThe first INR should be measured on day 3 after warfarin initiation, with the aim to identify high levels thereby maintaining caution with ongoing warfarin dosingPoint of Care INR should not be used to assess the INR during transition periodStop the Direct acting Oral Anticoagulant once INR is ≥ 2 on 2 consecutive days taking into account the effect of Direct acting Oral Anticoagulant on INR.Managing BleedingThe general principles for managing bleeding are described in Figure 1 (below), and include: Drug discontinuation – Anticoagulants should be ceased in anyone presenting with significant bleeding. The timing of recommencement will depend on the severity of bleeding, ongoing risk factors (e.g. poor renal function, anatomical lesions), and the initial indication for anticoagulation.Baseline laboratory assessment – Baseline assessment of haemoglobin should be done to assess severity of bleeding. Coagulation studies including PT, APTT and TT and where available specific drug levels should be performed to assess effect of drug on the coagulation system and to guide the need for intervention should be done. Creatinine Clearance will help predict drug clearance.General supportive measures – Surgical, endoscopic and radiological procedures to identify source and limit bleeding should be performed taking into account procedure related bleeding risk in an anticoagulated patient. Adequate hydration to enhance clearance of rivaroxaban and dabigatran should be maintained. Platelet transfusion may be considered in actively bleeding patients on concurrent anti-platelet therapy or if platelets are ≤ 50 x 109.Activated charcoal – This should be considered in patients with moderate to severe bleeding who present within 4 hours of last Direct acting Oral Anticoagulant dose.Administration of haemostatic agentsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UcmFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 7 – Current evidence on the use of pro-haemostatic agents in patients with dabigatran or rivaroxaban is limited. There is no published data on apixaban reversal currently. The risk and benefit of administration of haemostatic agents should be assessed in each individual patient. Until further information is available it is reasonable to consider their use in patients with life- or limb-threatening bleeding. The activated prothrombin complex concentrate Factor Eight Inhibitor Bypassing Activity (FEIBA?) and prothrombin complex concentrates (PCC) have been shown to reduce bleeding in animal models with variable effect on coagulation parameters in animals and healthy volunteers. Results with Recombinant factor VIIa (rFVIIa) are less consistent. Note that while PCC is stocked in the transfusion laboratory, FEIBA may not be available. Consultation with a haematologist is required.For patients on dabigatran presenting with severe, life threatening bleeding, or requiring surgery for a life threatening problem, specific reversal with idarucizumab should be considered. It is essential that bloods are taken for PT, APTT, TCT and dilute thrombin time prior to administration of idarucizumab, however if there is life threatening bleeding and the last dose is likely to have been within a time frame where significant drug activity is still likely to be present, the dose does not need to be delayed waiting for results. Approval by a haematologist is mandatory and early consultation is advised. Idarucizumab is stored in the transfusion laboratory and in Main Pharmacy. The usual dose is 5g (2 x 2.5g vials) intravenously over 5-10 minutes. Repeated dosing is not usually required, however repeat coagulation testing following the dose is recommended to evaluate coagulopathy.There are currently NO established strategies for immediate reversal of Direct acting Oral Anticoagulant effect.Figure 1: Management of Direct Acting Oral Anticoagulant Associated BleedingPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UcmFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 7,10* There are no clinical studies showing an improvement in clinical bleeding with Prothrombinex or FEIBA. **FEIBA is not routinely stocked at Canberra Hospital.Back to Table of Contents Section 6 – Perioperative Management of AnticoagulationIn the perioperative setting it is important to establish the risks of bleeding and thromboembolism as well as weigh the risk versus benefit of ceasing anticoagulation. ProcedureAssessment of all patients on anticoagulation with planned surgery should occur in the preadmission clinic or for inpatients as soon as the need for surgery becomes apparent. Assessment will occur using the following process, with the tool in Attachment 1 – Perioperative Anticoagulation Guidelines.Determine if anticoagulant needs to be stopped. Many minor procedures may be performed in patients on anticoagulation.Consider delaying surgery. For patients with recent thromboembolic events or on short courses of anticoagulation, there may be value in delaying surgery to minimise the risk.Assess the surgical bleeding risk.Determine the time to cease anticoagulation, if required.Determine whether bridging anticoagulation is required.Determine the type and dose of bridging anticoagulation, if required.Recommence anticoagulation post operatively.Back to Table of Contents Section 7 – Management of Bleeding in Anticoagulated PatientsAs bleeding in anticoagulated patients can be excessive, specific measures to arrest bleeding (surgical, angiographic or endoscopic) should be undertaken as soon as possible.Procedure Consider Reversal of Anticoagulants Where Possible:Warfarin reversal should be managed as per Section 3 with phytomenadione and prothrombin complex concentrates. PCC is available from the transfusion laboratory.Heparin has a short half life and in most cases ceasing heparin infusion will enable rapid reversal (over approximately 4 hours). In the event that more immediate heparin reversal is required, protamine may be given at a dose of 1mg for every 100 units of heparin to be neutralised over 10mins. Protamine must be given with caution. Sudden hypotension and anaphylaxis may be seen. Excessive dosing may exert an anticoagulant effect.LMWH are not fully reversible. In the event of bleeding after a recent dose of LMWH, partial reversal of LMWH with protamine may be indicated. A dose of protamine 1mg for every 1mg of enoxaparin (if given in the previous 8 hours) should be given. Patients on dabigatran with severe or life threatening bleeding may benefit from reversal with idarucizumab. There is no specific reveral agent for oral Xa inhibitors at this time. Specific advice for bleeding patients on direct acting oral anticoagulants is found in Section 5. Over-AnticoagulationWhere over-anticoagulation is contributing to bleeding (for example, INR>6), the risk of thromboembolism is high and the bleeding is not life threatening, partial reversal may be considered. In all other cases, complete warfarin reversal is recommended, recommencing anticoagulation once haemostasis has been obtained.Supportive CareGeneral supportive care, including fluid resuscitation, blood transfusion and inotropic support should be provided.Coagulation SupportCoagulation support with FFP and platelet transfusion may need to be considered, especially in the event of massive transfusion or concurrent use of antiplatelet agents. While the administration of FFP and cryoprecipitate is usually directed by the results of coagulation studies, these may be prolonged, and not reversible, with the use of Direct acting Oral Anticoagulants. Haematology advice should be sought. Maintaining HaemostasisConsider activation of the Critical Bleeding Massive Transfusion- Adults Procedure if haemostasis cannot be adequately maintained.Back to Table of Contents Section 8 – Diagnosis and Management of Heparin Induced Thrombocytopenia (HIT)ProcedureConsider HITHIT should be considered if the platelet count begins to drop 5-10 days after exposure to heparin although it can occur more rapidly (24 hours) in someone exposed to heparin in the preceding 100 days. Other potential causes of thrombocytopenia need to be considered. The 4T’s score is a useful re test probability scoring system to estimate the likelihood of HIT (see Table 15 below).Table SEQ Table \* ARABIC 15 - The “4T's” Score ADDIN EN.CITE <EndNote><Cite><Author>Ruf</Author><Year>2011</Year><RecNum>249</RecNum><DisplayText><style face="superscript">10</style></DisplayText><record><rec-number>249</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">249</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ruf, K. M.</author><author>Bensadoun, E. S.</author><author>Davis, G. A.</author><author>Flynn, J. D.</author><author>Lewis, D. A.</author></authors></contributors><auth-address>University of Kentucky HealthCare, Chandler Medical Center, Lexington, KY 40536, USA. kmruf2@uky.edu</auth-address><titles><title>A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia</title><secondary-title>Thromb Haemost</secondary-title></titles><periodical><full-title>Thromb Haemost</full-title></periodical><pages>553-9</pages><volume>105</volume><number>3</number><edition>2011/01/26</edition><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Algorithms</keyword><keyword>False Positive Reactions</keyword><keyword>Female</keyword><keyword>Heparin/ chemistry</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Probability</keyword><keyword>Retrospective Studies</keyword><keyword>Thrombin/antagonists & inhibitors</keyword><keyword>Thrombocytopenia/ chemically induced</keyword><keyword>Thrombosis</keyword></keywords><dates><year>2011</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0340-6245 (Print)
0340-6245 (Linking)</isbn><accession-num>21264443</accession-num><urls></urls><electronic-resource-num>10.1160/th10-09-0610</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10Points012Timing of platelet count fallPlatelet count fall < 4 days without recent heparin exposureConsistent with fall at 5-10 days but not clear (missing platelet count) or onset > day 10 or fall ≤ to 1 day with prior heparin exposure within past 30-100 days. Clear onset at days 5-10, or ≤ 1 day if prior heparin exposure within 30 days.ThrombocytopeniaPlatelet count fall < 30% or nadir < 10 x 109/LPlatelet count fall 30-50% or nadir 10-19 x 109/LPlatelet count fall > 50% and nadir > 20 x 109/LThrombosis or other sequelaeNoneSuspected thrombosis, but not proven, or non necrotising skin lesionsConfirmed new thrombosis, skin necrosis, or acute systemic reaction post- IV unfractionated heparin bolus Other causes of Thrombocytopenia presentDefinitePossibleNone apparentPre test probability score:6-8: High probability of HIT4-5: Intermediate probability0-3: Low probabilityLaboratory DiagnosisIf HIT is suspected the Haematology Service should be contacted. HIT screening tests should be ordered. False positive HIT screening tests can occur in a variety of clinical situations. The diagnosis of HIT requires interpretation of both clinical and laboratory results. Specialised assays may not be readily available, and patients may need to be pre-emptively treated for HIT prior to results being available. ManagementCease all heparin products, including heparin solutions used to flush venous catheters and locks for line patency.Consult a haematologist.Cease warfarin if it has been started and consider giving phytomenadione.Anticoagulation with non-heparin agent like danaparoid or Direct Acting Oral Anticoagulants MUST be commenced.Danaparoid Use in Patients with HIT ADDIN EN.CITE <EndNote><Cite><Author>MIMS</Author><Year>2015</Year><RecNum>247</RecNum><DisplayText><style face="superscript">6</style></DisplayText><record><rec-number>247</rec-number><foreign-keys><key app="EN" db-id="pseax52au2spagesfz55ssrxezptref2pzex">247</key></foreign-keys><ref-type name="Electronic Book">44</ref-type><contributors><authors><author>MIMS</author></authors></contributors><titles><title>MIMS Online</title></titles><dates><year>2015</year><pub-dates><date>March 2015</date></pub-dates></dates><urls><related-urls><url> 0.6mL ampoule of danaparoid contains 750 anti-Xa units.Therapeutic AnticoagulationLoading dose (IV bolus followed by infusion)Dose adjustment for Danaparoid IV bolus according to body weightTable 16 (below) gives dose adjustment for danaparoid IV bolus according to body weight. The bolus dose of danaparoid should be followed by a danaparoid infusion of 400units/hour for 4 hours, then danaparoid 300units/hour for 4 hours, then danaparoid 200units/hour. Subsequent danaparoid dose adjustments should be made to keep anti-Xa activity between 0.5 – 0.8units/mL.Preparation of Infusion:Table SEQ Table \* ARABIC 16 – Danaparoid IV Bolus According to Body WeightBody WeightDanaparoid Dose< 60kg1500 units60 – 75kg 2250 units75 – 90kg 3000 units> 90 kg3750 units MaintenanceAfter initial IV therapy conversion to a subcutaneous route can be considered after 4-5 days particularly if patient is well enough for discharge and INR post warfarin anticoagulation is not yet therapeutic.Table SEQ Table \* ARABIC 17 - Maintenance Dose According to Body WeightBody WeightDanaparoid Dose< 55kg500 units SUBCUT twice daily55 – 90kg 2250 units SUBCUT twice daily> 90kg1500 units SUBCUT three times dailyProphylaxisBody WeightDanaparoid Dose≤ 90kg750 units SUBCUT twice daily> 90kg1250 units SUBCUT twice dailyThe total daily dose of danaparoid should be reduced by 25 - 50% in patients with severe renal impairment i.e. CrCl <30 mL/minute.Danaparoid dosing in Renal Replacement Therapy Dialysis every other day or less frequently Danaparoid 3,750 units intravenous bolus before first two occasions of haemodialysis then dosing varies according to pre-dialysis plasma anti-factor Xa activity Danaparoid 3,000 units IV bolus (if pre-dialysis plasma anti-factor Xa levels <0.3 units/mL) or danaparoid 2,500 units IV bolus (if pre-dialysis plasma anti-factor Xa levels 0.3-0.35 units/mL) or danaparoid 2,000 units IV bolus (If pre-dialysis plasma anti-factor Xa levels 0.35-0.4 units/mL). If patient < 55kg Danaparoid 2,500 units IV bolus before first two occasions of haemodialysis then danaparoid 2,000 units IV bolus (if pre-dialysis plasma anti-factor Xa levels <0.3 units/mL) or danaparoid 1,500 units IV bolus (if pre-dialysis plasma anti-factor Xa levels 0.3-0.35 units/mL) or danaparoid 1,500 units IV bolus (If pre-dialysis plasma anti-factor Xa levels 0.35-0.4 unit/mL). For Daily DialysisDanaparoid 3,750 units IV bolus before first dialysis then danaparoid 2,500 units before the second dialysis. If patient < 55kg Danaparoid 2,500 units IV bolus before first dialysis then danaparoid 2,000 units before the second dialysis. Aim for plasma anti-Xa level of < 0.3 units/mL pre-dialysis and 0.5 – 0.8 units/mL during dialysis.Locking lines in patients with HITCitrate or Danaparoid are preferred. Back to Table of Contents Section 9 – Anticoagulation in PregnancyWarfarin is a known teratogen, especially peroconceptually and during the first trimester. The use of Direct acting Oral Anticoagulants is contraindicated during pregnancy. The management of anticoagulation in pregnancy will need to be individualised for women, based on their willingness to accept risk and inconvenience given the paucity of data in this setting.Procedure Prior to PregnancyThe need for anticoagulation should be reviewed prior to pregnancy.Women on long term anticoagulation should have a plan for anticoagulation developed in consultation with their treating specialist (cardiologist/haematologist, etc) and/or foetal medicine specialist.Women attempting pregnancy should be advised to have frequent pregnancy tests and switch from warfarin as soon as pregnancy is confirmed. his approach is safe, provided warfarin is ceased in early pregnancy (within 6 weeks of last menstrual period).For women who have a desire to avoid warfarin at all in pregnancy, and who are willing to accept the inconvenience of injections, switching to LMWH while attempting pregnancy may be considered. 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ADDIN EN.CITE.DATA 11Thromboprophylaxis is indicated during pregnancy in women with:Antiphospholipid Syndrome, including recurrent miscarriages, unexplained foetal death (after 10 weeks gestation), with prophylactic LMWH and aspirin;Prior idiopathic or oestrogen-associated (pregnancy, oral contraceptive pill associated) VTE;High risk thrombophilia (homozygous FV Leiden, AT deficiency, multiple thrombophilia) with a family history of thrombosis. Some guidelines recommend therapeutic anticoagulation in women with AT deficiency and a positive family history;Women with a prior history of a single VTE associated with a transient risk factor (other than hormonal, for example, surgery) do not require VTE prophylaxis during pregnancy, but should be vigilant for symptoms of VTE;VTE during pregnancy should be initially treated with therapeutic LMWH during pregnancy, and for at least 6 weeks post-partum, for a total duration of therapy of at least 3 months; For women requiring long term anticoagulation, LMWH in a therapeutic dose should be continued throughout pregnancy, using a daily or twice daily regimen;Mechanical heart valves require anticoagulation to be maintained throughout pregnancy. Once pregnancy is confirmed, warfarin should be ceased and low molecular weight heparin commenced on a twice a day dosing regimen. Dosing is initially based on pre-pregnancy weight, however as clearance can change during pregnancy, dosing may be adjusted according to measurement of anti-Xa levels to achieve a 4 hour post-dose level of 0.4-1 units/mL. After the first trimester, warfarin may be recommenced.Peri partumAll women requiring anticoagulation during pregnancy require a plan to manage delivery. In general, it is preferable to induce an elective delivery so that an anticoagulation management can be planned. Women on warfarin in the second and third trimesters will need bridging anticoagulation. Women using LMWH should have it withheld to enable delivery with minimal anticoagulant effect. For guidance on withholding or bridging anticoagulation see Section 6 on perioperative anticoagulation.Women requiring prophylactic or therapeutic anticoagulation during pregnancy should have anticoagulation recommenced once bleeding is controlled.PostpartumThe postpartum period carries a higher risk of VTE.Prophylactic anticoagulation should be considered in women at high risk of VTE (see also VTE Risk Assessment and Prophylaxis Guide). These include:Prolonged bed rest in the ante partum period;Excessive blood loss (>1000mL) with surgery;Blood transfusion;Concurrent medical conditions including SLE, heart disease, sickle cell disease;Postpartum infection;High risk thrombophilia (antithrombin deficiency, homozygous FV Leiden or prothrombin mutations, combined thrombophilic conditions) Prophylaxis should also be considered in women who have any two of the following:BMI>30kg/m2;Post partum haemorrhage >1000mL;SmokingAny thrombophiliaPre-eclampsiaFoetal growth retardation.Extended prophylaxis for 6 weeks is advised in all women requiring prophylaxis during pregnancy and may be considered for selected women with multiple risk factors.Women on long term warfarin therapy may have this reintroduced after delivery. Breast feeding is not a contraindication to warfarin.Direct acting Oral Anticoagulants should not be commenced or recommenced in breast feeding women.Back to Table of Contents Implementation Email notification to all medical staff Back to Table of ContentsReferencesRietbrock S, Heeley E, Plumb J, et al: Chronic atrial fibrillation: Incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme. Am Heart J 156:57-64, 2008Burridge N. D, D.: Australian Injectable Drugs Handbook, (ed 5th). Colligwood, Society of Hospital Pharmacists, 2011Keeling D, Baglin T, Tait C, et al: Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol 154:311-24, 2011Tran HA, Chunilal SD, Harper PL, et al: An update of consensus guidelines for warfarin reversal. Med J Aust 198:198-9, 2013Gallus AS, Baker RI, Chong BH, et al: Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis. Med J Aust 172:600-5, 2000MIMS: MIMS Online, 2015Tran H, Joseph J, Young L, et al: New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J 44:525-36, 2014Reilly PA, Lehr T, Haertter S, et al: The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol 63:321-8, 2014District SLH: Anticoagulation Guideline, in Health (ed). Sydney, NSW Health, 2014Ruf KM, Bensadoun ES, Davis GA, et al: A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia. Thromb Haemost 105:553-9, 2011Bates SM, Greer IA, Middeldorp S, et al: VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e691S-736S, 2012Back to Table of ContentsAbbreviations AbbreviationTerminologyAPTTActivated Partial thromboplastin timeINRInternational normalised ratioVTEVenous thromboembolismDOACDirect acting Oral AnticoagulantLMWHLow molecular weight heparinPTProthrombin timeFBCFull Blood CountHITHeparin Induced ThrombocytopeniaAFAtrial FibrillationTTThrombin time (also called Thrombin clotting time) PCCprothrombin complex concentratesBMIBody Mass IndexHITTSHeparin induced thrombosis-thrombocytopenia syndrome non-valvular AF non-valvular atrial fibrillation (Patients with atrial fibrillation without valvular heart disease or a prosthetic heart valve.Back to Table of ContentsSearch Terms Venous thrombosis, Pulmonary embolism, Venous thromboembolism, Anticoagulation, Heparin, Warfarin, Rivaroxaban, Apixaban, Dabigatran, DanaparoidBack to Table of ContentsAttachmentsAttachment 1: Perioperative Anticoagulation GuidelinesDisclaimer: This document has been developed by ACT Health, <Name of Division/ Branch/Unit> 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 Health Directorate assumes no responsibility whatsoever.Disclaimer: This document has been developed by ACT Health, Canberra Hospital and Health Service 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 Health Directorate assumes no responsibility whatsoever.Date AmendedSection AmendedApproved By24 June 2016Figures and AttachmentsCHHS Policy Team Manager31 August 2017Updates to section 9 content and scope.CHHS Policy Committee ChairAttachment 1 – Perioperative Anticoagulation Guidelines ................
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