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Please use current guidelines available on the UHNM intranet for patient treatment
Please use current guidelines available on the UHNM intranet for patient treatment
INDICATIONS
- Anticoagulation in patients with heparin induced thrombocytopenia (HIT)
- see Heparin induced thrombocytopenia guideline
- Argatroban is the preferred alternative anticoagulant in patients with HIT with critical illness, increased bleeding risk, extensive thrombosis, or potential need for urgent procedures
- Fondaparinux or a DOAC are reasonable options in clinically stable patients at low to average risk of bleeding (off licence use)
- Thrombocytopenia is not a contraindication to anticoagulation in HIT
- For advice, contact consultant haematologist
ARGATROBAN
- Preferred alternative anticoagulant in critically ill patients with suspected or proven HIT (with/without thrombosis)
- Direct thrombin inhibitor with a half-life of 50 min
- Eliminated by hepato-biliary route
Administration
- Check baseline platelet count and APTT
- No dose modification in patients with renal impairment
- Specific dosage protocol for patients on haemodialysis, contact haematologist
- Use with caution in patients in critical care and hepatic impairment (e.g. Child Pugh class B)
- Contraindicated in patients with severe hepatic impairment https://www.mdcalc.com/calc/340/child-pugh-score-cirrhosis-mortality (e.g. Child Pugh class C)
- No proven reversal agent - if patient bleeds, contact consultant haematologist
IV infusion by syringe pump
- Preparation: 50 mg/50 mL (1 mg/mL) solution for infusion - ready to use
- Administer via a syringe driver
Dosage
- Maximum dose 10 microgram/kg/min
- Check APTT 2 hr after initiation of infusion
Table 1: Argatroban dosage for HIT
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Standard dosing schedule Initial infusion rate 2 microgram/kg/min
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Critically ill/hepatic impairment Initial infusion rate 0.5 microgram/kg/min |
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APTT ratio | Infusion rate change | Next APTT | Infusion rate change | Next APTT |
<1.5 | Increase by 0.5 microgram/kg/min | 2 hr | Increase by 0.1 microgram/kg/min | 4 hr |
1.5-3.0 | No change | 2 hr; after 2 consecutive APTTs within target range, check at least once daily | No change |
4 hr; after 2 consecutive APTTs within target range, check at least once daily |
>3.0 | Stop infusion until APTT between 1.5–3.0; resume at half previous infusion rate and monitor | 2 hr | Stop infusion until APTT between 1.5–3.0; resume at half previous infusion rate and monitor | 4 hr |
DOACS
- DOACs are preferred for clinically stable HIT patients (with/without thrombosis) at low to average bleeding risk
- Use is off licence but supported by major international guidelines
- Rivaroxaban has been most studied in this area - if contraindicated, discuss alternative DOAC with consultant haematologist
Contraindications
- Same in HIT and VTE
- DOACs contraindicated in pregnancy and breastfeeding
- If eGFR <15 mL/min (30 mL/min for dabigatran), contraindicated
- If eGFR <50 mL/min, discuss with haematologist and renal physician
Rivaroxaban
- HIT with thrombosis - 15 mg 12-hrly for 21 days then 20 mg once daily
- HIT without thrombosis - 15 mg 12-hrly until platelet count >150 x 109/L then 20 mg once daily
- All doses to be taken with food
DANAPAROID
- Danaparoid is a low-molecular-weight heparinoid, chemically distinct from heparin
- Use to treat suspected or proven HIT (with/without thrombosis)
- consider when argatroban is contraindicated
- Use to prevent venous thrombosis in patients with a history of HIT
- No proven reversal agent - if patient bleeds, contact consultant haematologist
Administration
- For patients undergoing dialysis, discuss with haematology
- Check baseline platelet count and APTT
Bolus preparation
- Take 4500 units (3.6 mL of 1250 units/mL) danaparoid sodium injection
- make up to 45 mL in a syringe with sodium chloride 0.9% or glucose 5% = 100 units/mL
- The diluted solution is stable for 24 hr
Dosage
Table 2: Danaparoid dosing for HIT
Clinical indication | Danaparoid dosing schedule | ||
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Treatment of HIT (suspected or proven) whether associated with thrombosis or not Use IV bolus followed by IV infusion. Determine bolus dose from body weight |
Body weight <55 kg |
Body weight 55-89 kg |
Body weight ≥90 kg |
Bolus 1250 units (12.5 mL) |
Bolus 2500 units (25 mL) |
Bolus 3750 units (37.5 mL) |
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Followed by IV infusion 400 units/hr for 2 hr, then 300 units/hr for 2 hr, then 200 units/hr for 5 days | |||
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Prevention of venous thrombosis in patients with history of HIT | 750 units (0.6 mL of 1250 units/mL) SC every 12 hr |
FONDAPARINUX
- Use in HIT is unlicensed. Seek haematology advice before prescribing
- consider when argatroban contraindicated
- Use to prevent venous thrombosis in patients with a history of HIT
- Fondaparinux is an indirect anti-Xa inhibitor and has a half-life of 17-20 hr
- Avoid in patients with renal impairment with eGFR <30 mL/min, use argatroban instead
- if eGFR <50 mL/min, discuss with haematologist and renal physician
- Before starting, check baseline platelet count and APTT, renal function
- No proven reversal agent - if patient bleeds, contact consultant haematologist
Fondaparinux dosing for adult patients with HIT
- If body weight <50 kg, give 5 mg SC once daily
- If body weight 50-100 kg, give 7.5 mg SC once daily
- If body weight >100 kg, give 10 mg SC once daily
- If use in patients with renal impairment unavoidable, reduce dose and monitor anti-Xa levels - discuss with haematologist and renal physician
Prevention of VTE in patients with a history of HIT
- Give 2.5 mg SC once daily
Suspected HIT
- Whilst awaiting HIT testing results, consider prophylactic intensity fondaparinux 2.5 mg once daily in patients with suspected HIT with both of:
- an intermediate 4T score (10-15% likelihood of HIT). Scoring tool in HIT guideline
- high risk of bleeding and no other indication for therapeutic-intensity anticoagulation
BIVALIRUDIN
- Use in HIT is unlicensed. Seek haematology advice before prescribing
- Bivalirudin is a direct thrombin inhibitor licensed for use in coronary interventions
- it has a short half-life of 30–40 min which can be prolonged to 3 hr in patients with severe renal impairment
- for patients with renal impairment, use argatroban
- elimination of bivalirudin is by enzymic metabolism and renal excretion. No dose adjustment is required for hepatic impairment
- there is no known antidote
- rare cases of anaphylactic reaction have been associated with IV bolus or infusion
- Before starting infusion, obtain baseline platelet count and APTT
- No proven reversal agent - if patient bleeds, contact consultant haematologist
Preparation
- 250 mg powder for reconstitution for injection or infusion
Administration for HIT
- Check baseline platelet count and APTT, renal function
- Reconstitute each 250 mg vial with 5 mL water for injection
- swirl gently until completely dissolved and the solution is clear
- Withdraw 5 mL from the vial, and further dilute to a total volume of 50 mL with glucose 5% or sodium chloride 0.9%
- gives a final concentration of 5 mg/mL
- For HIT, given by intravenous infusion via infusion pump
Dosage for HIT
Table 3: Bivalirudin dosing for HIT for adult patients
Clinical indication | Bivalirudin dosing schedule | |
Patients with HIT with normal renal function |
0.2 mg/kg/hr IV continuous infusion Monitor APTT to achieve ratio 1.5–2.5 adjust infusion rate* |
|
Cr clearance | Infusion rate | |
Patients with renal impairment | 30-60 mL/min | 0.1 mg/kg/hr |
<30 mL/min | 0.05 mg/kg/hr | |
Monitor APTT to achieve ratio 1.5-2.5, adjust infusion rate* | ||
APTT ratio | ||
*APTT monitoring: 2 hr after start of infusion and after every change until stable. Thereafter check APTT once every 24 hr |
<1.5 | Increase infusion rate by 20% |
1.5-2.5 | No change | |
2.5-4 | (no bleeding), reduce infusion rate by 20% | |
>4 | Stop infusion, repeat APTT in 30 min and start infusion when APTT <2.5 at 50% reduced infusion rate |