EXAMPLES  Dalteparin, enoxaparin, tinzaparin

MECHANISM OF ACTION 

• Activate antithrombinIII(serine protease inhibitor)thus inhibiting factors IIa (thrombin) and Xa in the common pathway of the clotting cascade.
• Secondary effects mediated by impairing adhesion and aggregation of platelets.

INDICATIONS

• Prevention of VTE.
• Treatment of VTE and acute coronary syndrome/MI.
• Prevention of clotting in extracorporeal circuits

CAUTIONS AND CONTRA-INDICATIONS

• Heparin sensitivity.
• Haemophilia and other bleeding disorders.
• Severe hypertension.
• Severe hepatic or renal disease.
• In patients undergoing surgery on brain, eye or spinal cord

SIDE-EFFECTS

• Bleeding.
• Heparin-induced thrombocytopenia.
• Hypersensitivity reaction.
• Osteoporosis (long-term use)

METABOLISM AND HALF-LIFE

• Metabolised by heparinase in the liver and reticuloendothelial cells.
• Metabolites are excreted in the urine. t½ is 2–4h (prolonged in renal or hepatic failure).

MONITORING 

• Monitoring is not routinely required.
• In LMWH toxicity there is no effective antidote.

DRUG INTERACTIONS

• Increased risk of bleeding with NSAIDs (including aspirin), warfarin, clopidogrel and dipyridamole.
• Nitrate infusion reduces efficacy of LMWH

IMPORTANT POINTS

• Maximum plasma levels after subcutaneous injection are achieved more rapidly and bioavailability is improved.
• Shorter half-life (approximately half that of unfractionated heparin).
• Predictable response reduces the need for monitoring (monitored by measurement of anti-factor Xa activity instead of APTT in patients at increased risk of bleeding). As effective as unfractionated heparin in the prevention and treatment of venous thromboembolism and associated with fewer bleeding complications.
• Osteoporosis may occur in long-term use (usually >6 months)