Wednesday 21 June, 2006

How to use low molecular weight heparin

Posted in Emergency Dept., General Practice, Medicine, Michael Tam, Wards at 11:12 by Michael Tam

Index: Anticoagulation :: Printer friendly

Original article by: Michael Tam

The most commonly used low molecular weight heparin (LMWH) in Australia is enoxaparin sodium (Clexane). The other that is available is dalteparin sodium (Fragmin).

Personally, I like enoxaparin. It is easy to use, there is less monitoring required and for the most part, it can be used for most patients. There is good evidence that the low molecular weight heparins are better than unfractionated heparin in many settings where (full) therapeutic anticoagulation is required, e.g., in the acute treatment of venous thromboembolic (VTE) disease (1) and in acute coronary syndromes (2).

Some resources (e.g., ACCP recommendations (3) – see summary of guideslines) quote doses in terms of LMWH “units”. This is referring to units of anti-factor Xa (anti-Xa) activity. Enoxaparin sodium has approximately 100 units/mg of anti-Xa activity (4).

Like unfractionated heparin, LMWH are used for two purposes generally:

  1. Prophylaxis against venous thromboembolic disease (prophylactic dose);
  2. Full anticoagulation for treatment of thrombotic or thromboembolic disease (therapeutic dose).

Prophylactic dose

Many if not most inpatients in a teaching hospital with an acute medical or surgical condition are at increased risk of developing deep venous thrombosis (DVT) and VTE.

enoxaparin sodium 40 mg (4000 units) subcutaneously daily

See stratification of risk here (5).

  • For post-operative thromboprophylaxis on patients with moderate risk, enoxaparin sodium 20 mg subcutaneously daily, first dose 2 hours preoperatively (except for spinal/epidural anaesthesia).
  • For post-operative thromboprophylaxis on patients with high risk, enoxaparin sodium 40 mg subcutaneously daily, first dose 12 hours preoperatively (except for spinal/epidural anaesthesia).

Prior to commencement of enoxaparin, base line coagulation studies and platelet count should be performed. There is no need for monitoring of standard coagulation parameters as they are not affected by LMWH. The platelet count should be checked in 3-4 days and weekly if prolonged use for heparin induced thrombocytopaenia (HITS).

Therapeutic dose

enoxaparin sodium 1 mg/kg subcutaneously bd

or

enoxaparin sodium 1.5 mg/kg subcutaneously daily

Baseline coagulation studies and platelet count should be performed. Monitoring of coagulation parameters is not required. The platelet count should be monitored for HITS.

Dosage in renal impairment

When I graduated medical school, the “conventional wisdom” was not to use LMWH in renal failure as it was excreted by the kidneys and there was no way of “monitoring” the degree of anticoagulation or to reverse it. Well, both of these statements are false. Anticoagulation with LMWH can be monitored (with anti-Xa assays – which have become much more readily available) and LMWH can be reversed (with protamine sulfate – though reversal is not complete as LMWH does have some antithrombin activity as well) (6).

In severe renal failure (creatinine clearance < 30 mL/min):

Prophylactic dose:

  • enoxaparin sodium 20 mg (2000 units) subcutaneously daily;
  • reduced from 40 mg daily.

Therapeutic dose:

  • enoxaparin sodium 1 mg/kg subcutaneously daily;
  • reduced from 1 mg/kg bd or 1.5 mg/kg daily.

Monitoring is recommended

No dosage changes are required for initiation of enoxaparin for mild to moderate renal impairment (creatinine clearance 30-80 mL/min) though monitoring should be considered.

Normogram for adjusting LMWH dosage

The following normogram (7) can be used for monitoring anticoagulation and dosage changes for enoxaparin sodium. Monitoring should be considered where the “standard” dose of enoxaparin may be inappropriate (e.g., renal failure, low body weight, children). Anti-Xa levels are used for monitoring anticoagulation with LMWH. They need to be taken 4 hours after the most recent dose.

anti-Xa level (units/mL) ? Hold Next Dose ? Dose Change ? Repeat anti-Xa level
< 0.35 No Increase by 25% 4 hours post next a.m. dose.
0.35-0.49 No Increase by 10% 4 hours post next a.m. dose.
0.5-1.0 No No change Once/week 4 hours post an a.m. dose.
1.1-1.5 No Decrease by 20% 4 hours post next a.m. dose.
1.6-2.0 3 hours Decrease by 30% Trough level pre next dose, then 4 hours post next a.m.dose.
> 2.0 Until anti-Xa level <0.5 units/ml Decrease by 40% Trough level pre next dose and if not <0.5 units/ml repeat BD.

Reference articles

(1) van Dongen CJJ, van den Belt AGM, Prins MH, Lensing AWA. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. The Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001100. [download PDF :: 437 Kb]

(2) Magee KD, Sevcik W, Moher D, Rowe BH. Low molecular weight heparins versus unfractionated heparin for acute coronary syndromes. The Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002132. [download PDF :: 259 Kb]

(3) Geerts WH., Pineo GF., Heit JA., et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 126(3 Suppl):338S-400S, 2004 Sep.

(4) Clexane and Clexane Forte [data sheet]. Medsafe; New Zealand Medicines and Medical Devices Safety Authority. Last updated 27 June 2005. [download PDF :: 40 Kb]

(5) Tang WH. Perioperative DVT Prophylaxis. EMedicine [electronic article]. Last updated October 13, 2004. http://www.emedicine.com/med/topic3164.htm

(6) Tam M. How to reverse low molecular weight heparin [electronic article]. The Medicine Box. Last updated 30 June 2006. [Link]

(7) Newall F., Monagle P., Titchen T. Anticoagulation Therapy Guidelines [electronic article]. Royal Children’s Hospital Melbourne Clinical Practice Guidelines. Last updated September 2001. http://www.rch.org.au/clinicalguide/cpg.cfm?doc_id=5151

Updated: Michael Tam (21 July 2006)

Please read the disclaimer

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4 Comments »

  1. David Harris said,

    Hi Michael,

    I am a bladder cancer patient who has completed a radical combined chemo/radiation protocol . I developed symptoms for DVT’S and PE’S soon after treatment for cancer stopped. I was hospitalised and started on Clexane 100mg 2 x daily. I have been told by my medical oncologist that I will be required to continue the clexane for a min of 6 months and may have to continue this medication for life. I am concerned that I cant find any trial information relating to the long term usage of this drug. In fact the manufactures websites seem to infer that for the treatment of DVT/PE clexane is used for 7 – 10 days in conjunction with Warfrin. Once the suitable anticoagulation level has been achieved the warfrin is then used exclusively. As you seem to be an advocate for the drug perhaps you may know if the long term usage is safe and perhaps point me at relevent trial data.

    Regards David

  2. Michael Tam said,

    Firstly: Please read the disclaimer

    I am not a general physician, a haematologist or a trainee in either of those specialties. The following is from my experience and what I understand of the treatment of this condition.

    I am definitely not an advocate for enoxaparin or low-molecular weight heparins in general. They, nevertheless, have their uses and advantages to other forms of anticoagulation.

    Now you are entirely correct that in the treatment of venous thromboembolic disease (e.g., DVTs or pulmonary emboli) that low-molecular heparins like enoxaparin (Clexane) are typically used as a stop-gap measure while longer term anti-coagulation is achieved with warfarin. The main advantage with warfarin is that it is taken orally in tablet form rather than subcutaneous injections.

    Nevertheless, low molecular weight heparins can be used for long term anticoagulation, especially in the context of cancer. See the article here for more information (1).

    References

    (1) Zacharski L., Prandoni P., Monreal M. Warfarin versus low-molecular weight heparin therapy in cancer patients. The Oncologist, Vol. 10, No. 1, 72-79, January 2005; doi:10.1634/theoncologist.10-1-72

  3. Dr. Silvia Baciu said,

    I would like to know – in the abscence of the possiblity of monitoring anti-Xa activity – if there is a renal threshold to change from enoxaparin to IV heparin in order to be safe and also therapeutic

  4. Michael Tam said,

    Firstly: Please read the disclaimer

    In the absence of being able to do monitoring, LMWH is contraindicated in acute renal failure/disease, and chronic kidney disease stages 4 and 5 (eGFR < 30 mL/min/1.73m2).


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