Products
Low-molecular-weight heparins are commercially available as injectable solutions, in the form of prefilled syringes, ampoules, and lancing ampoules. The active ingredients now commonly used in many countries were first approved in the late 1980s. Biosimilars are available in some countries. The active ingredients are abbreviated in English with the acronym LMWH (low molecular weight heparins).
Structure and properties
Low molecular weight heparins are salts of sulfated glycosaminoglycans, which are obtained by chemical or enzymatic depolymerization or fractionation of heparin. Heparin is an animal product derived from the intestinal mucosa of pigs. The average molecular weight of low molecular weight heparins is less than 8000 Da. For unfractionated heparin, it is about 15,000 Da. Heparins consist of alternating units of D-glucosamine and a uronic acid (D-glucuronic acid or L-iduronic acid). For the interaction with the drug target antithrombin, a pentasaccharide sequence is of importance, which is randomly distributed in the macromolecule. Low-molecular-weight heparins exist as white, hygroscopic powders and are readily soluble in water.
Effects
The low-molecular-weight heparins (ATC B01AB) have antithrombotic properties. The effects are due to binding and activation of antithrombin (synonym: antithrombin III). Antithrombin in turn inactivates clotting factor Xa in the blood clotting cascade. In contrast to standard heparin (unfractionated heparin), the low-molecular-weight heparins hardly interact with thrombin (factor IIa) and cause less bleeding. They have better pharmacokinetic and pharmacodynamic properties. These include higher bioavailability, longer half-life, predictable efficacy (no monitoring), and fewer adverse effects. Direct factor Xa inhibitors that can be administered perorally are also commercially available today.
Indications
Low-molecular-weight heparins are used for the prevention and treatment of thromboembolic diseases of venous origin (deep vein thrombosis, pulmonary embolism). They are used, for example, after surgical interventions, during dialysis, in bedridden (immobilized) patients, in heart disease and in cancer. Other indications include unstable angina and myocardial infarction (non-Q-wave myocardial infarction, STEMI).
Dosage
According to the SmPC. Drugs are usually injected subcutaneously and, less commonly, intravenously (IV bolus). Subcutaneous injection is also self-administered by patients after appropriate instruction. The dosage depends on the patient’s body weight.
Agents
- Dalteparin (Fragmin)
- Enoxaparin (Clexane)
- Nadroparin (Fraxiparine, Fraxiforte)
Not or no longer commercially available in many countries:
- Ardeparin
- Bemiparin
- Certoparin (Sandoparin, out of trade)
- Parnaparin
- Reviparin
- Tinzaparin
Contraindications
Contraindications include (selection):
- Hypersensitivity
- Severe coagulation disorders
- Acute, clinically significant bleeding
For complete precautions, see the drug label.
Interactions
Caution should be exercised when using other agents that affect blood clotting (antithrombotics, anticoagulants, NSAIDs).
Adverse effects
The most common possible adverse effects include bleeding, thrombocytopenia, a transient increase in liver enzymes, and local reactions at the injection site such as pain and a bruise (hematoma).
