Low molecular weight heparin use in primary care

Contraindications to enoxaparin

Enoxaparin is contraindicated for people with an allergy to enoxaparin or other LMWHs as well as for people with active bleeding and conditions with a high risk of haemorrhage such as recent haemorrhagic stroke.¹

It is also contraindicated if platelet count is less than, or equal to 50×10⁹/L, in bacterial endocarditis, uncontrolled or severe hypertension, severe hepatic or renal disease, angiodysplasia or following recent eye or CNS surgery (less than one month prior).

Prior to commencing enoxaparin

Prior to commencing therapy with enoxaparin it is recommended that all patients:²

1. Are weighed
2. Have their creatinine clearance calculated using the Cockcroft- Gault formula. The eGFR calculated by the laboratory can be used as an indicator of renal impairment but the creatinine clearance equation should be used to guide dosage adjustment
3. Have blood tests to make sure they have a normal coagulation profile (INR, APTT), platelet count and normal liver function

Table 1: Volumes of Clexane required for each prescribed dose

Patients without renal impairment:¹

Prophylaxis of venous thromboembolism: 40 mg daily

Treatment of venous thromboembolism:* 1.5 mg/kg once daily or 1 mg/kg twice daily

Patients with renal impairment:

Prophylaxis of venous thromboembolism: 20 mg daily

Treatment of venous thromboembolism: An initial standard dose of enoxaparin based on the patient’s actual body weight is used so that an effective concentration is achieved rapidly. However, for patients with reduced renal function (i.e. creatinine clearance less than 30 mL/min), subsequent doses require adjustment because of the risk of over-coagulation and bleeding.

Patients who are at extremes of weight

Dosing based on body weight is acceptable up to 150 kg, however there is evidence that a dose based on lean body weight may be more appropriate.⁴ Once daily treatment is not recommended in patients over 100 kg (maximum syringe size is 150 mg).

Monitoring of enoxaparin may be appropriate for those who are underweight or overweight and for those with impaired renal function

Anti-factor Xa may be used to monitor the anticoagulant effect of enoxaparin in patients with significant renal impairment or those at extremes of weight (e.g. below 45 kg or above 150 kg).¹ However anti-factor Xa monitoring is best managed by a specialist because it is not routinely available and results can be difficult to interpret.²

Haemorrhage

The risk of a significant bleed when using low molecular weight heparins is increased with:⁵

• Reduced creatinine clearance
• Number of enoxaparin doses received
• Increasing age
• Female gender
• Low body weight (< 45kg)
• Concurrent use of other drugs that affect haemostasis including aspirin, clopidogrel, warfarin or NSAIDs
• Previous peptic ulcer disease

Impaired renal function and prolonged use of enoxaparin were found to be significant predictors of bleeding in one New Zealand study. The authors suggested that current guidelines for dosing adjustment in renal impairment may be inadequate to minimise bleeding risk.⁶ Consider discussing treatment with a specialist for patients who have impaired renal function or require prolonged treatment with enoxaparin.

A patient who has received LMWH and is clinically bleeding, may be administered protamine in hospital. While protamine reverses approximately 70% of the activity of LMWH, it does reduce clinical bleeding. If enoxaparin was given within eight hours, then a dose of 1 mg of protamine per 1 mg of enoxaparin is given. Smaller doses are recommended if it is greater than eight hours since enoxaparin was administered (0.5 mg protamine for 1 mg enoxaparin).³

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is diagnosed when HIT antibodies are detected in conjunction with any of the following events: a decrease in platelet count of greater than or equal to 50%, venous or arterial thrombosis, skin reactions occurring at heparin injection sites or acute systemic (anaphylactoid) reactions that occur after IV heparin bolus administration.⁷

HIT occurs rarely with the use of LMWH, occurring three fold less frequently than with heparin.³ The frequency of HIT is highly variable and is influenced by: the reason the patient is receiving heparin (the risk is greatest post-surgery followed by use for medical patients, and lowest when used during pregnancy), duration of heparin exposure and gender (the risk is greater for females than males).

For people who are at higher risk of HIT (e.g. post-surgery, prolonged exposure, female) platelet count should be checked before initiation of enoxaparin, then regularly (every three to five days) during the initial stage of treatment. If HIT has not developed within the first month of treatment it is unlikely to occur.

For people at low risk of HIT, less frequent (or no) platelet count monitoring may be appropriate. All patients receiving enoxaparin should be instructed to contact their GP promptly if signs or symptoms of venous thromboembolism (the most common complication of HIT) occur or painful skin lesions develop at the injection sites.⁷