Section 3: Treatment of Venous Thromboembolism (VTE) with low molecular weight heparin (LMWH)

Before starting anticoagulation, please check baseline investigations- see SECTION 1: Introduction, and check if the patient has any of the following cautions or contraindications to anticoagulation. Please seek advice from the consultant and/or duty or on-call haematologist if needed.

• Acquired coagulopathy: seek advice from duty/on-call haematologist
  
  
• Acute gastro-duodenal ulcer
  
  
• Active bleeding of any sort
  
  
• Acute stroke
  
  
• Advanced liver disease
  
  
• Neurosurgery within the previous 3 months
  
  
• Inherited bleeding disorder e.g. haemophilia, von Willebrand
  
  
• Previous history of heparin-induced thrombocytopenia- please see Section 4 - UFH guidance (including HIT) within the Antithrombotic guide for more information
  
  
• Thrombocytopenia (platelet count less than 50 x 10⁹/L): dependent on causation of thrombocytopenia, seek advice from duty/on-call haematologist
  
  
• Severe renal impairment, increased bleeding risk when CrCl <30ml/min

Enoxaparin dosing

Enoxaparin is the choice of LMWH in NHS Borders. Patients should be weighed (kg) during admission and the weight should be documented in the patient’s notes within the “Multidisciplinary Assessment & Communication” booklet. Enoxaparin is administered as a subcutaneous (s/c) injection and comes in a 20mg, 40mg, 60mg, 80mg, 100mg, 120mg, and 150mg pre-filled syringe (PFS).

The two treatment tables below outline the treatment for VTE with enoxaparin guided by the indications, weight and renal function. Where available, calculated creatinine clearance (CrCl) should be used in preference over eGFR. Where this is unavailable, dose based on the patient’s eGFR results.

• For treatment of non-high-risk VTE with eGFR ≥30ml/min/1.73m², this is based on a dose of 1.5mg/kg ONCE daily. (Table 1)
  
  
• For patients with eGFR <30 ml/min/1.73m² regardless of non-high-risk or high-risk, the dose is based on 1mg/kg ONCE daily. (Table 1)
  
  
• For treatment of high-risk VTE, which is defined below, this is based on a dose of 1mg/kg TWICE daily. (Table 2)
  
  
• For patients who weigh ≥130kg, the dose is based on 0.85mg/kg TWICE daily. (Table 2)

Doses have been calculated and rounded to a fixed-dose pre-filled syringe.

Patients with eGFR <30ml/min/1.73m² and/or weigh ≥130kg should have Anti-Xa levels monitored (*) - please see section below for monitoring details.

For acute DVT/ PE, patients should be initiated on total of 7 days of treatment dose enoxaparin or apixaban 10mg TWICE daily. Where enoxaparin has been started, this can either be switched to apixaban 10mg TWICE daily to complete the 7 days or remain on enoxaparin for 7 days before reducing to apixaban 5mg TWICE daily. Treatment duration is usually around 3-6 months as guided by the clinician. For more information on apixaban, please see Section 5: DOACs for more information.

Patients being initiated on warfarin for their VTE should concurrently receive enoxaparin until INR is >2.0 for 2 consecutive days. For more information on warfarin, please see SECTION 6: Vitamin K antagonists  (Section 6 is currently being updated and will be available as soon as possible.)

Twice daily enoxaparin should be used for patients with eGFR >30ml/min/1.73m² who meet any of the following criteria:

• High risk VTE
  • Iliac vein DVT
  • Symptomatic PE- those not suitable for a DOAC
  • Initial treatment of cancer-associated VTE requiring LMWH for 5-10 days, then to revert to the treatment table above
  • Weight over 130kg
    
    
• Short term anticoagulation of arterial thrombosis
  
  
• Short term anticoagulation of atrial fibrillation
  
  
• Short-term anticoagulation of mechanical valves

Table 1 - Enoxaparin dosing for acute VTE (excluding active cancer or high-risk features)

Table 2 - Enoxaparin dosing for high-risk VTE

Enoxaparin monitoring

LMWH, such as enoxaparin, does not require routine monitoring since weight-adjusted dosing for treatment or prophylaxis usually provides a predictable clinical response.

Dosing may be unreliable in certain cohorts of patients due to limited published evidence. These include patients who:

• Are at extremes of body weight, i.e. <50kg, or >130kg
• Have severe renal impairment, e.g. eGFR < 30ml/min
• Are pregnant
• Have unexpected bleeding

In these situations, it might be prudent to check LMWH activity via Anti-Xa levels.

How to arrange a LMWH assay (Anti-Xa levels)

LMWH assays (Anti-Xa levels) are ordered on TrakCare as “Anti-Xa assay” (this will also appear if searching “LMWH assay”); samples are sent in a green citrated tube filled adequately to the level marked on the tube. There is no facility in NHS Borders for this, so Anti-Xa bloods are sent to NHS Lothian laboratories for processing. It may take 1-2 days for results to be returned on TrakCare, continue current dose until results return.

When to take a peak LMWH (Anti-Xa) assay

A peak Anti-Xa level should be taken after the third dose of LMWH has been administered, 3-4 hours following the administration of the drug.

Interpretation

For patients on once daily dosing, the expected peak plasma concentration is about 1.0 anti-Xa unit per mL (U/ml) with an acceptable range of 0.5 to 1.5 U/ml (and 0.5 to 1.0 U/ml for twice daily dosing). The duty/on-call haematologist can assist with dose adjustment if the level is out with acceptable range.

Platelet counts

All patients receiving LMWH should have a baseline platelet count. Most patients will not require routine monitoring – see Section 4 Unfractionated Heparin (UFH) and heparin-induced thrombocytopenia (HIT): Platelet count monitoring in patients receiving heparins for information on patient groups requiring further platelet monitoring.

Stockings are not required to be prescribed routinely but only used selectively in patients to treat symptoms.

Absolute contra-indications are:

• Advanced peripheral arterial occlusive disease
• Decompensated heart failure
• Septic phlebitis
• Phlegmasia caerulea dolens (DVT leading to severe swelling of the whole leg)

Relative contra-indications are:

• Suppurative dermatoses
• Intolerance of compression stocking fabric
• Advanced neuropathy
• Chronic arthritis