Low Molecular Weight Heparins ( LMWH ) to treat Venous Thromboembolism in Adults - Guidance on the use of Treatment Dose

Publication: 01/09/2012  
Next review: 11/12/2022  
Clinical Guideline
CURRENT 
ID: 3212 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guidance on the use of Treatment Dose Low Molecular Weight Heparins to treat Venous Thromboembolism in Adults

Summary

Enoxaparin is the low molecular weight heparin (LMWH) of choice at Leeds Teaching Hospitals (LTHT). LMWHs for the treatment of venous thromboembolism must be dosed using a patient’s current weight and renal function. Anti-factor Xa levels are not routinely needed in most patients to guide dosing but are useful in patients with poor renal function (CrCl <30ml/min), in pregnant patients and in patients weighing > 150kg. All patients should have a baseline platelet count prior to commencing LMWH.

Flow chart for treatment dose low molecular weight heparin

The maximum dose of enoxaparin recommended once daily is 200mg. Patients over 137kg should receive 200mg stat then 1mg/kg twice a day to a maximum of 150mg twice daily. Patients over 150kg should be monitored with anti-factor Xa levels 3-4 hours after the third dose - see later for further details.

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Background

LMWHs are used when parenteral anticoagulation is required for the following

  • for the treatment of venous thrombosis any site,
  • acute coronary syndrome,
  • arterial thrombosis,
  • anticoagulant bridging for patients undergoing surgery who are on warfarin or patients on warfarin with a high thrombotic risk who have a subtherapeutic INR
  • when oral anticoagulation cannot be used
  • prevention of venous thromboembolism.

LMWHs are given by subcutaneous injection1. This guidance concentrates specifically on the treatment of venous thromboembolism. The following LMWHs are used to treat thromboembolic events at LTHT:

  • Enoxaparin (Inhixa®) agent of choice
  • Tinzaparin (Innohep®) for paediatrics and patients who cannot tolerate enoxaparin

Unfractionated heparin may also be used to treat thromboembolic events in patients with a CrCl <20mL/min or those who need an anticoagulant that is rapidly reversible.  Please refer to the heparin (unfractionated) intravenous prescription chart for use in adults or consult your pharmacist for advice on dosing and monitoring.

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Diagnosis

Please refer to the Guideline for Investigation and Initial Management of Venous Thromboembolism (VTE) in Leeds Teaching Hospitals (LTH) http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=3962 and guidance on cancer associated thrombosis http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=1208

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Dosing considerations

Patient weight
When used for the treatment of a thromboembolic event the dose of LMWH is dependent on the actual weight of the patient and the renal function. It is important to obtain an accurate weight in kilograms (kg) at the start of therapy and during treatment (if the weight is likely to change) and to document this on PPM+ and eMeds to avoid over and under dosing and the risks associated with this. If the weight changes the dose should be recalculated unless the patient has been dosed on anti-factor Xa levels. Ideal body weight or adjusted body weight should not be used for dosing LMWH.

When patients are unable to stand or are confined to their beds, equipment such as hoists with weighing scales or under-bed weighing systems are available to measure their weight accurately. The GP system on PPM+ may have an up to date weight and should be checked if the patient cannot be weighed. The NPSA has published information showing that in exceptional circumstances when a patient cannot be weighed, obtaining body weight from patients (or carers) has been shown to be a more reliable source of information than estimates by healthcare staff2. Use of total body weight is appropriate for therapeutic doses of LMWHs in obese patients3.

For patients who need urgent anticoagulation when an accurate weight is not available the dose should not be withheld but an accurate weight is required for subsequent doses.

Renal Function
Renal function must be considered when prescribing treatment doses of LMWHs as LMWHs are renally cleared. The renal function test should not delay the initiation of the first dose but every effort must be made to base subsequent dosing on renal function. LTHT have used enoxaparin in patients with severe renal dysfunction or patients on dialysis for a number of years. More recently the SPC states enoxaparin should not be used in patients with a CrCl < 15ml/min. LTHT Thrombosis Steering Group agreed to continue to use enoxaparin in these patients due to the wealth of expertise that had been gained already in this area. LMWHs must be used with caution in patients with renal failure due to the risk of accumulation and therefore bleeding. Anti-factor Xa monitoring is required, see later.

Please use the Cockcroft and Gault equation to calculate the creatinine clearance (CrCl)

The calculator can be found by the following link http://nww.lhp.leedsth.nhs.uk/Calculators/Renal/index.aspx

Adding in the patient’s height for patients who are overweight can give a creatinine clearance calculation based on ideal or adjusted body weight as well as actual weight.

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Treatment / Management

Treatment of DVT/PE in all adult patients

The LMWH of choice to treat VTE in adult patients at LTHT is currently enoxaparin

Dose of enoxaparin
Full anticoagulation of patients with a diagnosis (or working diagnosis) of DVT/PE

Dose in adults: Enoxaparin 1.5mg/kg bodyweight once daily up to a maximum of 200mg once a day.

Administration: Administration is by subcutaneous injection.

Please note there are a variety of different volumes and strengths of enoxaparin syringes available. Please make sure you have selected the correct one.

Standard strength 100mg/ml

  • 0.2ml syringes (containing enoxaparin 20mg)
  • 0.4mL syringes (containing enoxaparin 40mg)
  • 0.6mL syringes (containing enoxaparin 60mg)
  • 0.8mL syringes (containing enoxaparin 80mg)
  • 1.0mL syringes (containing enoxaparin 100mg)

High strength 150mg/ml

  • 0.8mL syringes (containing enoxaparin 120mg)
  • 1.0mL syringes (containing enoxaparin 150mg)

Enoxaparin dosing for patients with creatinine clearance > 30ml/min.

Body
Weight (kg)

Dose (mg) via subcutaneous injection

37kg - 44kg

60mg ONCE daily

44.1kg - 50kg

70mg ONCE daily

50.1kg - 57kg

80mg ONCE daily

57.1kg - 64kg

90mg ONCE daily

64.1kg - 70kg

100mg ONCE daily

70.1kg - 77kg

110mg ONCE daily

77.1kg - 84kg

120mg ONCE daily

84.1kg - 90kg

130mg ONCE daily

90.1kg - 97kg

140mg ONCE daily

97.1kg - 104kg

150mg ONCE daily

104.1kg - 110kg

160mg ONCE daily

110.1kg - 117kg

170mg ONCE daily

117.1kg - 124kg

180mg ONCE daily

124.1kg - 130kg

190mg ONCE daily

130.1kg - 137kg

200mg ONCE daily

>137kg - 150kg

200mg STAT then 1mg/kg bd starting 18-24 hours post dose

>150kg

200mg STAT then 150mg bd starting 18-24 hours post dose with anti factor Xa monitoring 3-4 hours after 3rd dose

For doses over 150mg 2 syringes will be required. Try to use whole syringes where possible.

Patients with recurrent thrombosis on therapeutic anticoagulation, patients with a VTE provoked by Covid-19 and patients with a very large thrombotic burden i.e. massive/submassive PE not requiring thrombolysis should receive a stat dose of 1.5mg/kg maximum 200mg then 1mg/kg twice daily starting 18-24 hours after the stat dose.

Dose in renal impairment

CrCl less than or equal to 30mL/min: Enoxaparin 1mg/kg once a day with anti-factor Xa monitoring or unfractionated heparin

Method of administration

If the dose is less than the whole syringe you must get rid of any extra liquid. Hold the syringe upright, with the needle pointing upwards. Gently press in the plunger so any extra liquid is pushed out. If supplying to a patient for self administration do not pre-prepare the syringe, supply the whole syringe to the patient with instructions on how to remove the extra liquid.

If the dose uses the whole syringe you may notice a small air bubble in the syringe. You do not need to remove this. The syringe is ready to use.

Time of administration

Enoxaparin should be administered once daily with a 24 hour dosing interval or twice daily with a 12 hour dosing interval. If the time of administration needs to be changed this can be done by moving the time forward by 2 hours each day or 2 hours back each day until the new administration time has been reached.

If a patient on LMWH requires an epidural catheter or spinal anaesthesia please refer to Clinical Practice Guidelines for the delivery of Epidural and Paravertebral Analgesia in Adult Acute Pain Management

Duration of treatment

Most patients requiring treatment for VTE will be switched to an oral anticoagulant. For further advice on switching and on duration of anticoagulation refer to the Guidance for Starting and Maintaining Adult Patients on oral anticoagulants5 or Direct oral anticoagulants for the treatment of VTE
http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=3974 or the cancer associated thrombosis guideline http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?id=1208

Further guidance can be found on the Leeds anticoagulant and VTE resource pages.

Treatment of DVT/PE in all paediatric patients

Please refer to the Guideline for the use of Anti-thrombotic Treatment in Children6 which is available on Leeds Health Pathways.

Contraindications

This list is not exhaustive, further advice may be obtained from haematology, internal departmental guidance (some areas e.g. elderly) or the Summary of Product Characteristics

  • Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients
  • Haemophillia and other haemorrhagic disorders
  • History of heparin induced thrombocytopenia (HIT)
  • Thrombocytopenia - discuss with haematology (see cancer associated thrombosis guideline for platelets < 50 x109/L)
  • Active clinically significant bleeding and conditions with a high risk of haemorrhage, including
    • recent haemorrhagic stroke,
    • active gastrointestinal ulcer,
    • presence of malignant neoplasm at high risk of bleeding,
    • recent brain, spinal or ophthalmic surgery,
    • known or suspected oesophageal varices,
    • arteriovenous malformations,
    • vascular aneurysms or
    • major intraspinal or intracerebral vascular abnormalities
  • Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for treatment in the previous 24 hours

Serious caution

  • Uncontrolled severe hypertension
  • Acute infective endocarditis

Please seek specialist advice from haematologists to discuss patients with an acute VTE that have any of the above contraindications.

Monitoring

Anti-factor Xa
Monitoring of LMWH therapy is only necessary in specific situations, for example in chronic kidney disease, CrCl <30ml/min or weight extremes e.g. patients who are morbidly obese (BMI >40kg/m2), weight > 150kg.

An anti-factor Xa level of 0.5 - 1 unit/mL 3-4 hours after a dose is recommended for VTE treatment.

For treatment of VTE in pregnancy please refer to an obstetrician specialising in the management of VTE in pregnancy and the following guideline Protocols for the Diagnosis and Management of Acute Venous Thromboembolism in Pregnancy and the Puerperium7.

Please contact haematology for further advice if the anti-factor Xa levels have been taken at an appropriate time but are not within the desired range.

Platelets and potassium

All patients who are to be prescribed LMWH should have a baseline platelet count8.

Post-operative patients (other than cardiopulmonary bypass patients) receiving LMWH do not need routine platelet monitoring8.

Medical patients and obstetric patients receiving heparin do not need routine platelet monitoring8.

Post-cardiopulmonary bypass patients receiving LMWH should have platelet count monitoring performed every 2–3 days from days 4 to14 or until heparin is stopped8.

Post-operative patients and cardiopulmonary bypass patients who have been exposed to heparin in the previous 100 days and are receiving any type of heparin should have a platelet count determined 24 hours after starting heparin8.

  • If the platelet count falls by 30% or more and/or the patient develops new thrombosis or skin allergy between days 4 and 14 of heparin administration or any of the other rarer manifestations of heparin induced thrombocytopenia, heparin induced thrombocytopenia (HIT) should be considered and a clinical assessment made8. For further information on the management of HIT please refer to the guideline for The management of heparin-induced thrombocytopenia and thrombosis9. After 14 days of treatment HIT is very unlikely.

Please consult Haematology for advice if there are particular concerns regarding monitoring on discharge for patients on prolonged courses of enoxaparin or those patients with a previous history of thrombocytopenia.

Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis or taking medicinal products known to increase potassium. Plasma potassium should be monitored prior to starting LMWH and after a week of therapy. Regular monitoring monthly for patients at risk should be considered.

Discharge and transfer of care

Reports to the National Reporting and Learning System (NRLS) indicate that lack of information at transfers of care has led to reports of harm2. For patients being discharged on LMWH please ensure dosage, indication, intended duration of treatment, patient’s weight and follow up plan are documented on the eDAN. For new VTE events in in-patients please complete a thrombosis clinic referral form found on the VTE pages of LHP.

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Provenance

Record: 3212
Objective:

To provide evidence-based recommendations to promote a safe and consistent approach to the use of treatment dose low molecular weight heparins for the treatment of venous thromboembolism. It addresses the need to use the patient’s most up to date weight and renal function to determine the dose of low molecular weight heparin to be prescribed and the importance of communicating this information at any transfer of care. It aims to provide a practical guide for medical and other healthcare professionals involved in the use of treatment dose low molecular weight heparins.

Clinical condition:

Venous Thromboembolism

Target patient group: All adult patients who require Management of Venous Thromboembolism
Target professional group(s): Pharmacists
Secondary Care Doctors
Adapted from:

Evidence base

  1. Joint Formulary Committee. British National Formulary 68th edition.  London: British Medical Association, Royal Pharmaceutical Society of Great Britain. 2014.
  2. National Patient Safety Agency Rapid Response Report NPSA. 2010, Reducing treatment dose errors with low molecular weight heparins. Available at www.nrls.nhs.uk/alerts (accessed: 2/09/2010)
  3. Edith EN, et al. Low molecular weight heparins in renal impairment and obesity available evidence and clinical practice recommendations across medical and surgical settings. Annals of Pharmacotherapy. 2009 43(6). pp. 1064-83
  4. Leeds Teaching Hospitals. 2021. Anticoagulant- Guidance for starting and maintaining adult patients on anticoagulants. [Online]. Available from: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=1409
  5. Leeds Teaching Hospitals. 2019. Guideline for the Use of Anti-thrombotic Treatment in Children.[Online]. Available from: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=1667
  6. Leeds Teaching Hospitals. 2020. Protocols for the Diagnosis and Management of Acute Venous Thromboembolism in Pregnancy and the Puerperium. [Online]. Available from: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=2178
  7. Keeling,D., Davidson, S., Watson, H. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition - BJH Guideline. British Society for Haematology. 2012
  8. Leeds Teaching Hospitals. 2020. Guideline for the management of heparin-induced thrombocytopenia and thrombosis. [Online]. Available from: http://nww.lhp.leedsth.nhs.uk/common/guidelines/detail.aspx?ID=1407
  9. Enoxaprin (Inhixa) SPC https://www.medicines.org.uk/emc/product/782/smpc#gref accessed 27/04/2021

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 2.1

Related information

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