Low Molecular Weight (LMW) Heparins

LOW MOLECULAR WEIGHT (LMW) HEPARINS

Heparin has been fractionated into LMW forms (MW 3000–7000) by different techniques. LMW heparins have a different anticoagulant profile; selectively inhibit factor Xa with little effect on IIa. They act only by inducing conformational change in AT III and not by bringing together AT III and thrombin. As a result, LMW heparins have smaller effect on aPTT and whole blood clotting time than unfractionated heparin (UFH) relative to antifactor Xa activity. Also, they appear to have lesser antiplatelet action—less interference with haemostasis. Thrombocytopenia is less frequent. A lower incidence of haemorrhagic complications compared to UFH has been reported in some studies, but not in others. However, major bleeding may be less frequent. The more important advantages of LMW heparins are pharmacokinetic:

• Better subcutaneous bioavailability (70–90%) compared to UFH (20–30%): Variability in response is minimized.

• Longer and more consistent monoexponential t½: once daily s.c. administration.

• Since aPTT/clotting times are not prolonged, laboratory monitoring is not needed; dose is calculated on body weight basis.

Most studies have found LMW heparins to be equally efficacious to UFH. Indications of LMW heparins are:

1. Prophylaxis of deep vein thrombosis and pulmonary embolism in highrisk patients undergoing surgery; stroke or other immobilized patients.

2. Treatment of established deep vein thrombosis.

3.  Unstable angina.

4. To maintain patency of cannulae and shunts in dialysis patients, and in extracorporeal circulation.

A number of LMW heparins have been marketed. They differ in composition, pharmacokinetics and dosage.

Enoxaparin: CLEXANE 20 mg (0.2 ml) and 40 mg (0.4 ml) prefilled syringes; 20–40 mg OD, s.c. (start 2 hour before surgery).

Reviparin: CLIVARINE 13.8 mg (eq. to 1432 anti Xa IU) in 0.25 ml prefilled syringe; 0.25 ml s.c. once daily for 510 days.

Nadroparin: FRAXIPARINE 3075 IU (0.3 ml) and 4100 IU (0.4 ml) inj., CARDIOPARIN 4000 anti Xa IU/0.4 ml, 6000 anti Xa IU/0.6 ml, 100, 000 anti Xa IU/10 ml inj.

Dalteparin: 2500 IU OD for prophylaxis; 100 U/Kg 12 hourly or 200 U/Kg 24 hourly for treatment of deep vein thrombosis. FRAGMIN 2500, 5000 IU prefilled syringes.

Pamparin: 0.6 ml s.c. OD for unstable angina and prophylaxis of DVT; FLUXUM 3200 IU (0.3 ml), 6400 IU (0.6 ml) inj.

Ardeparin: 25005000 IU OD; INDEPARIN 2500 IU, 5000 IU prefilled syringes.

Fondaparinux: The pentasaccharide with specific sequence that binds to AT III with high affinity to selectively inactivate factor Xa has been recently produced synthetically and given the name fondaparinux. It has been marketed in USA and some other countries.