(e.g. inclusion and exclusion criteria, diagnosis) anticoagulation Future management of HIT patients post acute phase

Transcription

1 Title of Guideline (must include the word Guideline (not protocol, policy, procedure etc) Contact Name and Job Title (author) Guideline for the treatment of heparin induced thrombocytopenia (HIT) in adults Julian Holmes (Haemostasis and Thrombosis Pharmacist) Dr Joannes Hermans (Haemostasis and Thrombosis Consultant) Directorate & Speciality Cancer and associated specialities Date of submission June 2018 Date on which guideline must be reviewed (this should June 2021 be one to three years) Explicit definition of patient group to which it applies Adult patients with acute HIT requiring (e.g. inclusion and exclusion criteria, diagnosis) anticoagulation Future management of HIT patients post acute phase Abstract Key Words Statement of the evidence base of the guideline has the guideline been peer reviewed by colleagues? Evidence base: (1-5) 1a meta analysis of randomised controlled trials 1b at least one randomised controlled trial 2a at least one well-designed controlled study without randomisation 2b at least one other type of well-designed quasi-experimental study 3 well designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practice based on the clinical experience of the guideline developer Consultation Process Target audience Guideline for investigation and management of heparin induced thrombocytopenia in adults Argatroban, fondaparinux, warfarin, danaparoid, HIT, heparin, enoxaparin 1a, 1b, 1c, 2c, Based on BCSH guidelines on the diagnosis and management of HIT 2 nd edition Oct 2012 SPC for argatroban, fondaparinux and danaparoid Haemostasis and Thrombosis Service Drugs and Therapeutics Committee Renal (Dr Roe and Dr Bebb) All wards and clinical areas This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. Page 1 of 21

2 Heparin Induced Thrombocytopenia (HIT) Introduction Heparin-induced thrombocytopaenia (HIT) is an antibody-mediated reaction that can occur in patients receiving unfractionated heparin or rarely, low molecular weight heparins (LMWH). It typically presents 5-10 days after the start of heparin treatment, but can occur sooner if patients have had recent exposure to heparin. HIT involves the development of antibodies that bind to heparin- platelet factor 4 (PF4) complexes. This then causes platelet activation and also platelet binding to the endothelium in blood vessel walls causing thrombin release and thrombosis. The platelet count falls (often to <50 x 10 9 L and/or a fall >50% from previous count) but there is a paradoxical increased risk of potentially life-threatening thrombus formation. These events can occur more rapidly if a patient is re-challenged with heparin after a previous episode of HIT. Any patients with a suspected diagnosis of HIT MUST be discussed with a haematology consultant/registrar before any laboratory tests are ordered or treatment started. Please complete the 4T score (below) before contacting the Haematology team Investigation and Diagnosis of HIT HIT is predominantly a clinical diagnosis. The 4T score has been validated as a pretest probability score for the clinical likelihood of HIT. It should be calculated based on the reduction in platelet count, timing of thrombocytopenia, presence of thrombosis and whether there is any other cause for thrombocytopenia present. (BCSH guideline on diagnosis and management of HIT 2 nd Edition 2012). Table1: Calculation of 4T score Event Score =2 Score =1 Score = 0 Thrombocytopenia >50% fall and platelet nadir >20 x 10 9 L 30-50% fall or platelet nadir x 10 9 L Fall <30% or platelet nadir <10 x 10 9 L Timing of platelet count fall or other sequelae Thrombosis or other sequelae (e.g. skin lesions) OTher cause for thrombocytopenia not evident Clear onset between days 5-10 of treatment; or 1 day if previous heparin exposure within last 30 days New thrombosis, skin necrosis or post heparin bolus acute systemic reaction No other cause for platelet count fall is evident Consistent with immunization but not clear (eg missing platelet counts) or onset of thrombocytopenia after day 10; or 1 day if previous heparin exposure days ago Progressive or recurrent thrombosis, erythematous skin lesions or suspected thrombosis not yet proven Possible other cause is evident Platelet count fall too early ie 4 days (without recent heparin exposure) None Definite other cause is present Page 2 of 21

3 The result of the 4T score should be used to guide treatment as below whilst confirmatory testing is performed. Table 2: Action based on 4T score Score Likelihood of HIT Action 6-8 High Inform haematology. If appropriate treat as detailed below 4-5 Intermediate Discuss with haematologist 0-3 Low Consider alternative diagnoses. May continue heparin but review diagnosis frequently The diagnosis is confirmed by a positive laboratory test result. An initial screening test is performed and this is available 24 hours a day on both sites. This is followed by a confirmatory enzyme-linked immunosorbent assay (ELISA), which requires samples to be sent to the QMC Haemostasis and Thrombosis reference laboratory and is usually processed within working hours. All investigative tests should be discussed with a Haematologist before sending samples to the laboratory. Please refer to HIT report sheet (Appendix 1) and pre-test probability score sheet (Appendix 2). Treatment of HIT ALL HEPARIN MUST BE STOPPED (including flushes and heparin coated catheters). Platelets should NOT be routinely given as this may cause thromboembolism. In the event of life threatening bleeding, platelets are very rarely used but this must be discussed and approved by a Haematologist On stopping heparin the platelet count will usually recover but there is still a risk of thromboembolism for several days and even weeks afterwards. If the platelet count does not improve, the diagnosis should be reviewed and the patient discussed again with a Haematologist. Treatment for patients requiring anticoagulation involves the use of an anticoagulant that does not induce the production of HIT antibodies. Choice of anticoagulant If the patient s calculated creatinine clearance (Cockcroft-Gault see appendix 3) is >30ml/min fondaparinux should be used. Fondaparinux is contraindicated in patients with a creatinine clearance <30ml/min. In this clinical situation, argatroban should be used or second line danaparoid should be used if argatroban is not available. Appendix 7 summarises the treatment of acute HIT. Page 3 of 21

4 Fondaparinux Fondaparinux is a synthetic inhibitor of factor Xa that is unlikely to induce HIT antibodies. Use for this indication is off-label, but is supported by national and local guidance and has the advantage of once daily subcutaneous dosing rather than a continual intravenous infusion. (* Trust s unlicensed medicines policy should be followed) Patient weight (kg) and creatinine clearance>30ml/min <50kg kg >100kg Fondaparinux dose (mg) once daily s/c 5mg 7.5mg 10mg (reduced to 7.5mg on day 2 if creatinine clearance is 30-50ml/min) Fondaparinux at a treatment dose is contraindicated if the creatinine clearance is <30ml/min. Creatinine clearance can be calculated using the link: Page 4 of 21

5 Argatroban Argatroban is a direct thrombin inhibitor that reversibly binds to thrombin and inhibits the action of both free and clot associated thrombin. It does not interact with heparin induced antibodies. This should be used if the patient has renal impairment (creatinine clearance <30ml/min) or if the patient has had a previous episode of HIT and undergoing dialysis. (Creatinine clearance can be calculated using the link: Argatroban dosing Argatroban is available as 250mg in 2.5ml concentrate for IV infusion; this is diluted with 250ml sodium chloride 0.9% or glucose 5% to give a final concentration of 1mg/ml. Mix thoroughly after dilution by repeated inversion of the solution container for one minute. o Do not expose diluted solutions to direct sunlight (but no need to additionally cover) o Do not use after 24 hours. The initial infusion is 2microgram/kg/minute. o There is a reduced infusion rate for patients with moderate hepatic impairment (Child-Pugh class B), after cardiac surgery and critically ill patients of 0.5microgram/kg/minute. o Argatroban is contraindicated in patients with severely impaired hepatic function, uncontrolled bleeding and hypersensitivity to argatroban or any of the excipients (ethanol and sorbitol). Preferably administer via a central venous access device to avoid potential venous irritation as the preparation has a low ph. If a central venous access device is unavailable a risk benefit analysis should be made on an individual patient basis. If given peripherally, the insertion site should be monitored closely for phlebitis using a recognised infusion phlebitis scoring tool. Maximum recommended dose is 10microgram/kg/min and maximum treatment length 14 days (there is limited clinical experience of administration for longer periods). Half life is 52 minutes and time to steady state 1-3 hours Avoid concomitant use of thrombolytics or antiplatelets if antiplatelets are required discuss with cardiology or haematology Measure baseline aptt prior to commencing the infusion and adjust as below See appendix 4 for dosing during haemodialysis. Page 5 of 21

6 Body weight (kg) (round to nearest 10kg) Initial Infusion rate of Argatroban 1mg/mL (ml/hr) 2microgram/kg/min Argatroban Dose modifications 0.5microgram/kg/min Monitoring is via aptt - measure baseline aptt and then repeat 2 hours after the start of the infusion and adjust the infusion rate according to the table below. The target aptt is times the initial baseline value (but not exceeding 100seconds). Standard dosing schedule Initial infusion rate 2microgram/kg/min Critically ill/hepatically impaired patients Initial infusion rate 0.5microgram/kg/min aptt (s) Infusion rate change Next aptt Infusion rate change Next aptt <1.5 times baseline times baseline (not exceeding 100seconds) >3.0 times baseline or >100seconds Increase by 0.5microgram/kg/min No change Stop infusion until aptt is times baseline; resume at half the previous infusion rate 2 hours Increase by 0.1microgram/kg/min 2 hours; No change after 2 consecutive aptt s within target range check at least once per day 2 hours Stop infusion until aptt is times baseline; resume at half the previous infusion rate 4 hours 4 hours; after 2 consecutive aptt s within target range check at least once per day 4 hours Page 6 of 21

7 Danaparoid Danaparoid is a heparinoid composed of heparan sulphate, dermatan sulphate and chondroitin sulphate. It is chiefly an inhibitor of factor Xa and only exhibits rare cross reactivity to the antibodies that mediate HIT. It can be used second line if argatroban cannot be used or is unavailable. Danaparoid dosing Danaparoid is available in 750unit ampoules in 0.6ml for s/c or iv use. Ampoules may be diluted in any volume of sodium chloride 0.9% or glucose. ALL patients to receive initial bolus followed by infusion as detailed below. IV bolus IV infusion Monitoring 400units/hr for 2 hours then 300units /hr for 2 hours then 200units/ hr for 5 days <55kg 1250units 55-90kg 2500units 90kg 3750units Only measure anti Xa levels if creatinine clearance <20ml/min or patient >90kg Dilute 6 amps (4500units) in 500ml to give 9units/ml. Run this at 44 ml/hr for 2 hours then 33 ml/hr for 2 hours then 22 ml/hr for 5 days. For flush doses dilute 1 ampoule in 50ml saline. Levels units/ml 5-10mins after bolus, NOT higher than 1unit/ml in adjustment phase of infusion and units/ml during maintenance infusion Frequency of monitoring to be determined on individual patient basis Subsequent treatment of acute HIT The HIT diagnosis MUST be documented in the patient s medical notes and put on NOTIS as an alert. The patient must be informed of the diagnosis and counselled about the risk of recurrence if re-exposed to heparin/lmwh (e.g. enoxaparin), avoidance of heparin/lmwh (e.g. enoxaparin) in the future and alerting medical staff that they have previously had HIT. For patients with confirmed acute HIT, once the platelet count has been within the normal range for 2 consecutive days, oral anticoagulation with warfarin should be commenced. This should be started with a reduced loading dose (e.g.6mg, 6mg, 3mg): See Warfarin Loading Doses in Adults Guideline available from the Trust s Clinical Guidelines Page on the intranet ies/clinical%20haematology/2379.pdf Page 7 of 21

8 Patients being treated with fondaparinux HIT positive patients should continue to receive fondaparinux injection as detailed above along with oral anticoagulation, unless the patient is bleeding. Fondaparinux should be continued until two consecutive INR s above 2 have been attained and can then be stopped. Patients being treated with argatroban If the patient has received argatroban, once oral anticoagulation is indicated, they should commence warfarin. This should be started with a reduced loading dose and initially given concomitantly with argatroban. See Warfarin Loading Doses in Adults Guideline available from the Trust s Clinical Guidelines Page on the intranet (link). Concomitant use of warfarin and argatroban produces a combined effect on the INR test so when INR>4 discontinue argatroban as this correlates with an INR of 2-3 with warfarin alone. Patients being treated with danaparoid If the patient has received danaparoid once oral anticoagulation is indicated they should commence warfarin as above. The danaparoid infusion should be maintained until INR 1.5. If the risk of bleeding is high then: Stop the danaparoid sodium infusion and start danaparoid sodium 750 units SC BD. Then 24 hours later start warfarin. Continue the danaparoid sodium for hours to allow the INR to reach therapeutic levels. The INR must not be taken within 5 hours of the danaparoid sodium bolus being given. OR Stop the danaparoid sodium infusion and start warfarin 12 hours later. Patients with acute venous thrombosis If the patient had a VTE as a result of HIT warfarin should be given for the appropriate duration (depending on the VTE location). If the patient has HIT but no VTE warfarin should be given for at least 1 month. Page 8 of 21

9 Subsequent anticoagulation in patients with a history of HIT In patients with a previous history of HIT there exists a risk of recurrence with reexposure to heparins. There is some evidence for re-using heparin (after >100 days post HIT) but alternative anticoagulants with little or no risk of causing HIT should ideally be used. Any further re-exposure to heparin should ALWAYS be discussed with a Haematologist prior to commencing treatment. This includes low molecular weight heparin thromboprophylaxis. Subsequent VTE in patients with previous HIT If patients require anticoagulation for VTE and they have a history of HIT, they should not receive a heparin based anticoagulant. Advice should be sought from heamatology, but options include treatment doses of fondaparinux, danaparoid, argatroban or warfarin Thromboprophylaxis Patients who have had a previous episode of HIT and subsequently require thromboprophylaxis (e.g. in immobile medical and surgical patients) should receive prophylactic doses of fondaparinux 2.5mg s/c daily. This dose should be reduced to 1.5mg s/c once daily in patients with a creatinine clearance of 20-30ml/min. Fondaparinux at a prophylactic dose is contra-indicated in patients with a creatinine clearance of <20ml/min. Alternatively danaparoid can be used at prophylactic doses of 750units s/c twice daily (three times daily if >90kg). Monitoring of anti Xa is not routinely required (unless <55kg or >90kg or in renal failure), but if necessary levels should be 0.2Units/ml on day 1 and Units/ml at steady state, with levels taken halfway between doses. Levels should not exceed 0.4Units/ml. Pregnancy HIT in pregnancy should be discussed with Haematology. Patients with previous HIT in pregnancy should be referred to the obstetric haematology clinic in any subsequent pregnancies; this service is available on both City and QMC sites. Haemodialysis patients Appendix 4 gives the argatroban dosing for anticoagulation during haemodialysis for patients with acute or previous HIT. PCI patients Appendix 5 gives the argatroban dosing for patients with HIT undergoing PCI Page 9 of 21

10 Danaparoid in dialysis Appendix 6 gives the danaparoid dosing for patients in dialysis for acute HIT, a previous history of HIT or an intolerance of heparins Summary of acute HIT treatment Appendix 7 summarises the treatment of acute HIT. Anticoagulation in patients with a history of HIT Appendix 8 outlines anticoagulation in patients with a history of HIT References Argatroban (Exembol) Mitsubishi Pharma Europe Summary of Product Characteristics [updated ] on Electronic Medicines Compendium: (accessed on [ ]) via Drugdex System. Thomson Micromedex, Greenwood Village, Colorado accessed via [July 2014] Fondaparinux (Arixtra) and Danaparoid Aspen trading. Summary of Product Characteristics [ updated ] on Electronic Medicines Compendium: (accessed on [ ]) via Guidelines on the diagnosis and management of Heparin induced thrombocytopenia: second edition 2012 (BCSH Page 10 of 21

11 Appendix 1: HIT report sheet HEPARIN INDUCED THROMBOCYTOPENIA (HIT) Questionnaire ALL HIT requests MUST be discussed with a member of the Haematology medical team before the request will be accepted IT IS ESSENTIAL THAT THE FOLLOWING INFORMATION IS FAXED BACK TO OR SENT WITH THE SAMPLE BEFORE TESTING FOR HIT WILL BE UNDERTAKEN Haematology doctor contacted regarding this request Pre test probability score Patient Name DOB Hospital No Ward (please circle) Previous THREE platelet counts Date. Count. x10 9 /l Date. Count. x10 9 /l Date. Count. x10 9 /l Current (or recent) heparin administered Type.. Date started.. Date stopped.. Previous heparin administered in last 100 days (document all exposure) Type.. Date started.. Date stopped.. Type Date started Date stopped Does the patient have a THROMBOTIC event? Yes / No If YES, please specify.. NOTE: SAMPLE REQUIRED FOR HIT SCREENING IS 1 PLAIN CLOTTED (SERUM) SAMPLE. SSTR GEL TUBES CANNOT BE USED Page 11 of 21

12 Appendix 2: HIT pre-test probability scoresheet Diagnosis of HIT This is by using the pre-test probability score (four T s see below), based on clinical suspicion, a reduction in the platelet count, unexplained thromboembolic problems and positive laboratory test results. Circle and score all that apply to patient: Event Score =2 Score =1 Score = 0 Thrombocytopenia >50% fall and platelet nadir >20 x 10 9 L 30-50% fall or platelet nadir x 10 9 L Fall <30% or platelet nadir <10 x 10 9 L Timing of platelet count fall or other sequelae Thrombosis or other sequelae (e.g. skin lesions) OTher cause for thrombocytopenia not evident Clear onset between days 5-10 of treatment; or 1 day if previous heparin exposure within last 30 days New thrombosis, skin necrosis or post heparin bolus acute systemic reaction No other cause for platelet count fall is evident Consistent with immunization but not clear (eg missing platelet counts) or onset of thrombocytopenia after day 10; or 1 day if previous heparin exposure days ago Progressive or recurrent thrombosis, erythematous skin lesions or suspected thrombosis not yet proven Possible other cause is evident Platelet count fall too early ie 4 days (without recent heparin exposure) None Definite other cause is present Score Likelihood of HITT Action 6-8 High Inform haematology. If appropriate treat as detailed in HIT guideline. 4-5 Intermediate Discuss with haematologist 0-3 Low May continue heparin but review diagnosis frequently Patient name DOB Hospital number Ward Haematologist contacted Form completed by: Name/Signature Date Contact number Page 12 of 21

13 Appendix 3: Calculation of Cockroft Gault Creatinine Clearance CrCl (ml/min) = (140 age) x weight (kg) x 1.04 (female) or 1.23 (male) serum creatinine (micromol/l) Appendix 4: Argatroban dosing for anticoagulation during haemodialysis for patients with acute or previous HIT Argatroban can be used for haemodialysis anticoagulation though there is limited data for its use Use initial bolus of 250microgram/kg followed by continuous infusion of 2microgram/kg/min. See page 4 for information on how to prepare the infusion and the table below for dosing. Stop infusion 1 hour before the end of dialysis Target Activated Clotting Time (ACT) range is seconds using the Haemotec device. In patients already on argatroban no bolus dose is required (i.e. continue the infusion at the existing rate). Argatroban is not extensively cleared during haemodialysis and continuous venovenous haemofiltration. Body weight (kg) (round to nearest 10kg) Haemodialysis bolus dose of 250microgram/kg given over 3-5 minutes Bolus dose (microgram) Volume of 1mg/ml solution (ml) Infusion rate of Argatroban 1mg/mL (ml/hr) 2microgram/kg/min Page 13 of 21

14 Appendix 5: Argatroban in patients with HIT undergoing PCI There is limited data for HIT patients undergoing PCI. Dilute argatroban to give a solution of 1mg/ml. See page 4 for information on how to prepare the infusion. A bolus dose of 350microgram/kg over 3-5 minutes followed by an infusion of 25microgram/kg/min has been used. Check Activated Clotting Time (ACT) 5-10 minutes after bolus dose completed and proceed with procedure if ACT greater than 300seconds. ACT value If ACT below 300 seconds If therapeutic ACT of seconds achieved If ACT higher than 450 seconds Action Give additional bolus dose of 150microgram/kg and increase infusion rate to 30microgram/kg/min and re-check ACT 5-10 minutes later Continue infusion for duration of procedure Decrease infusion rate to 15microgram/kg/min and re-check ACT 5-10 minutes later There is no data on use of argatroban in combination with GPIIb/IIIA inhibitors Dosing schedules as in tables below: Bolus Doses: Body weight (kg) (round to nearest 10kg) Initial bolus dose of 350microgram/kg given over 3-5 minutes Bolus dose (microgram) Volume of 1mg/ml solution (ml) If ACT<300 seconds additional bolus dose of 150microgram/kg given over 3-5 minutes Bolus dose (microgram) Volume of 1mg/ml solution (ml) Page 14 of 21

15 See table above for 350microgram/kg dose See above table for 150microgram/kg dose Infusion Rates: Body weight (kg) Initial infusion 25microgram/kg/min (ACT seconds) If ACT<300 seconds Dose adjust infusion to 30microgram/kg/min If ACT >450 seconds Dose adjust to 15microg/kg/min (round to nearest 10kg) Initial Infusion Bolus dose dose (microgram/ min) Infusion rate (ml/hr) Bolus dose Infusion dose (microgram/ min) Infusion rate (ml/hr) Infusion dose (microgram/ min) Infusion rate (ml/hr) Page 15 of 21

16 Appendix 6: Danaparoid dosing in dialysis for acute HIT, a previous history of HIT or an intolerance of heparins Alternate day haemodialysis Danaparoid 3750units bolus (2250units if <55kg) before 1 st and 2 nd dialyses. Anti Xa levels should be performed prior to each dialysis session. Levels should be between Units/ml for the first 3 dialysis sessions Subsequent doses are then given according to pre-dialysis anti Xa level: Anti Xa level Units/ml Danaparoid dose if >55kg Danaparoid dose if <55kg < units 2000units units 1500units units 1500units >0.4 (measure anti Xa prior to next dialysis to determine dose) 0units 0units During dialysis the target anti Xa level is units/ml. If during dialysis fibrin threads are seen or clotting occurs then a 1500unit bolus should be given irrespective of body weight. When 3 consecutive dialyses require the same dose of danaparoid then a steady state has been reached and subsequent dialyses can proceed with the same predialysis dose without the need for an anti Xa level. However anti Xa levels should be carried out at least once every 3-4 sessions to ensure there is no accumulation. CAPD Patients <90kg 750units twice daily Patients >90kg 750units three times daily or 1250units twice daily Anti Xa levels should be 0.2units/ml on day 1 and units/ml at steady state (with levels taken mid way between doses) and should not exceed 0.4units/ml. An anti Xa level should be taken prior to each dialysis. Daily haemodialysis Anti Xa levels should be taken prior to each dialysis. Danaparoid 3750units bolus (2250units if <55kg) before 1 st dialysis Danaparoid 2250units (2000units if <55kg) before 2 nd dialysis Doses for the 3 rd and subsequent dialyses are guided by the anti Xa levels as described for alternate day haemodialysis above. Page 16 of 21

17 If the anti Xa level is too high and a danaparoid has to be omitted then the predialysis dose for the next dialysis should be the same as the previous dose prior to the omitted dose. Haemofiltration (CVVHF or CAVHF) Use the danaparoid regimen for the acute treatment of HIT (page 2), the maintenance infusion rate may need to be >200units/h during the first hours. The steady state anti Xa levels should be between 0.5 and 1units/ml. It has not been established if danaparoid passes through filters with molecular weight cut-offs of 10,000 Daltons. The dose rate depends on the weight of the patient, the presence of residual heparin in the circulation and the patency of the filter in relation to the filtration rate required. These factors must be balanced against the bleeding risk in the patient. Danaparoid can be introduced into the afferent circuit to the filter instead of directly into a vein. In principle the lowest maintenance danaparoid infusion rate compatible with acceptable filter performance should be aimed for. Page 17 of 21

18 Appendix 7: Acute HIT treatment summary Positive diagnosis of HIT Requiring anticoagulation treatment Creatinine clearance >30ml/min Creatinine clearance <30ml/min or undergoing dialysis or PCI Treat with fondaparinux s/c once daily or danaparoid iv infusion See guideline page 4 (fondaparinux) and page 6 (danaparoid and appendix 6) for full information Treat with argatroban iv infusion: reduced infusion rate for patients with moderate hepatic impairment (Child- Pugh class B), after cardiac surgery and critically ill patients. Contraindicated in patients with severely impaired hepatic function, uncontrolled bleeding and hypersensitivity to argatroban or any of the excipients (ethanol and sorbitol). See guideline page 5 for full information and appendices 4 or 5 as applicable ALL patients to be started on oral coumarin anticoagulants unless contra-indicated (once the platelet count has returned to normal for 2 days?) not immediately Fondaparinux should be continued until INR >2 on 2 consecutive days. Danaparoid should be continued until INR>1.5 Argatroban should be continued until INR >4 on 2 consecutive days. (Concomitant use of warfarin and argatroban produces a combined effect on the INR test so when INR>4 this correlates with an INR of 2-3 with warfarin alone.) Page 18 of 21

19 Appendix 8 Anticoagulation in patients with a history of HIT Subsequent Event Either Or VTE If patient weight: <50kg fondaparinux 5mg s/c OD kg fondaparinux 7.5mg s/c OD >100kg fondaparinux 10mg s/c OD (reduced to 7.5mg on day 2 if CrCl 30-50ml/min) and warfarinise Treatment doses of argatroban or danaparoid (as above) and warfarinisation Thromboprophylaxis (e.g. for surgery) Non-ST elevation acute coronary syndromes (i.e. ACS; unstable angina [UA] and non-st elevation [non-q wave] myocardial infarction [NSTEMI]) N.B. Fondaparinux C/I if CrCl <30ml/min fondaparinux 2.5mg s/c OD (if CrCl = 20-30ml/min fondaparinux 1.5mg s/c OD) N.B. Fondaparinux C/I if CrCl <20ml/min fondaparinux 2.5mg s/c OD N.B. Fondaparinux C/I if CrCl <20ml/min Danaparoid 750units s/c BD (TDS if >90kg) Page 19 of 21

20 Equality Impact Assessment Report 1. Name of Policy or Service Response to external best practice policy 2. Responsible Manager Owen Bennett (Clinical Quality, Risk and Safety Manager) 3. Name of person Completing EIA Julian Holmes 4. Date EIA Completed Description and Aims of Policy/Service Treatment of heparin induced thrombocytopenia (HIT) 6. Brief Summary of Research and Relevant Data BCSH guideline on diagnosis and management of acute HIT 2 nd edition Oct Methods and Outcome of Consultation N/A 8. Results of Initial Screening or Full Equality Impact Assessment: Equality Group Age Gender Race Sexual Orientation Religion or belief Disability Dignity and Human Rights Working Patterns Social Deprivation Assessment of Impact No Impact Identified No Impact Identified No Impact Identified No Impact Identified Danaparoid is derived from porcine gut mucosa Argatroban contains alcohol No Impact Identified No Impact Identified No Impact Identified No Impact Identified Page 20 of 21

21 9. Decisions and/or Recommendations (including supporting rationale) From the information contained in the procedure, and following the initial screening, it is my decision that a full assessment is not required at the present time. 10. Equality Action Plan (if required) N/A 11. Monitoring and Review Arrangements Review June 2021 Page 21 of 21