Principal Developer: G. Pineo
Secondary Developers: C. Demers, M.F. Scully

What is Heparin?

Heparin is an anionic mucopolysaccharide.

Heparin acts as an anticoagulation by forming a complex with antithrombin, catalysing the inhibition of several activated blood coagulation factors: XIIa, XIa, IXa, Xa and thrombin.

Heparin is most commonly used for prevention and treatment of venous and arterial thromboembolism.

Heparin’s onset of action is immediate. It is most often uses in acute conditions, and must be given parenterally.

Apparent Uses of Heparin Therapy

Although low molecular weight heparin has become the treatment of choice for patients with venous thromboembolism, unfractionated heparin by continuous intravenous infusion is still commonly used in patients with massive pulmonary embolism, for patients who are unstable or may require interventional procedures or thrombolysis. Furthermore, intravenous heparin is commonly used for patients with cardiovascular disease, following angioplasty, coronary artery bypass surgery, thrombolysis or peripheral vascular surgery. Intravenous heparin is favoured in the above cases because the effect can be rapidly reversed by discontinuing the intravenous infusion or, where necessary, administering protamine sulfate.

Monitoring Heparin Therapy

The aPTT is used to monitor the effects of heparin treatment. APTT reagents vary considerably in their sensitivity to heparin, therefore your laboratory should establish a therapeutic range locally. However, a reasonable estimate of an adequate therapeutic effect would be achieved by an aPTT ratio of 1.5-2.5 times control corresponding to a Factor Xa level of 0.35-0.70 u/ml. Inadequate heparin therapy in the initial 24-48 hours of treatment predisposes to recurrent venous thromboembolism.

Practical Guidelines

• Do baseline CBC, PT, aPTT, plt count
• Give IV Bolus 5,000 U infusion or 80 U/kg,
• start infusion with initial rate of at least 1,300 U/hr or 32,000 U/24 hrs, or 18 U/kg/hour
• Monitor aPTT every 6 hours until therapeutic range is achieved (refer to Establishing Therapeutic Range of Heparin).
• Thereafter monitor aPTT and platelet counts daily

Dosage Adjustments

The use of a heparin dosing nomogram is encouraged because it helps achieve and maintain the aPTT in the therapeutic range efficiently. Two examples of heparin dosing nomograms which could be used in de novo patients are shown below.

BOLUS

5,000 U is given IV followed by IV infusion.

MAINTENANCE

IV infusion

Adapted from Hull et al. Arch Intern Med 1992; 152: 1589-1595.

MAINTENANCE

IV infusion – weight -based nomogram

Adapted from Raschke et al, Ann Intern Med 1993; 199: 874-881.

• These nomograms do not apply to patients following thrombolysis.
• The concentration of heparin used in these nomograms was 20,000 units per 500 ml sol.
• Local modification may be necessary depending on the local aPTT reagent used.
• APTT should be monitored every 4-6 hours during the first 24 hours, and daily thereafter unless it is subtherapeutic.

Overlap with Warfarin

In most cases, warfarin can be started on the same day as heparin. Warfarin and heparin should overlap for at least 5 days or until the INR value is within therapeutic range for two consecutive days before heparin is discontinued.

Pregnancy

Heparin is used for the management of thromboembolism during pregnancy although LMWH has become the drug of choice in most centres in Canada. Depending on the indication, prophylactic or therapeutic heparin can be achieved by subcutaneous injections twice daily. Heparin should be stopped at the first sign of labour. For therapeutic doses, most centres electively induce these patients and stop heparin 24 hours before induction. Secondary prevention in the post-partum period can be achieved with warfarin or SC LMWH and is recommended for at least 6 weeks after delivery. Women can breast feed while being treated with warfarin therapy.

The management of pregnant women who have previously had a DVT or PE is controversial. Heparin 5,000 q12h subcutaneously or heparin adjusted to produce a heparin level of 0.1-0.2 U/ml throughout pregnancy are recommended for high risk patients. The more common approach is to use LMWH. This will be discussed in the guideline on pregnancy.

Adverse Effects

Bleeding is the most common adverse effect of heparin.

If major bleeding occurs, discontinue heparin. The administration of 10-20 mg of Protamine Sulfate IV (over at least 5 minutes) may be used to neutralize heparin’s effects.

With less critical bleeding, doses should be adjusted and underlying causes investigated.

Osteoporosis is a serious, but less common side-effect associated with prolonged use of high doses of heparin. Three months of heparin treatment with moderate dose (20,000 U/ 24 hrs) will most likely not be associated with clinically significant osteoporosis.

Thrombocytopenia – platelet count reduction is, in most cases, asymptomatic but may be associated with life-threatening or fatal arterial or venous thrombosis.

A small percentage of patients treated with heparin will develop heparin induced thrombocytopenia (HIT). For this reason it is very important to check platelet counts regularly in all patients receiving heparin even in prophylactic doses. HIT usually begins between 4 and 7 days after commencing therapy. Should it occur, stop all sources of heparin and, if necessary, alternative treatment with Danaparoid or Lipirudin followed by warfarin may be used. Argatroban will also become available in 2002. Platelet counts usually return to baseline within 4 days of stopping therapy.

References:

1. Ginsberg et al. Chest 2001; 119(1): 122S-131S.
2. Hirsh et al. Chest 2001; 119(1): 8S-21S.
3. Hyers et al. Chest 2001; 119(1): 176S-193S.
4. Hull et al. Arch Intern Med, 1992; 152: 1589-1595.
5. Raschke et al. Ann Intern Med 1993; 119: 874-881.
6. Warkentin et al. Thromb Haemost 1998; 79: 1-7.