Low Molecular Weight Heparins (LMWH)

Summary

Low molecular weight heparins are anticoagulant drugs that share many similarities to regular or unfractionated heparin. Like regular heparin, low-molecular weight heparins work by activating antithrombin III, which causes it to selectively inhibit the clotting actions of factor 10-A. This drug class includes enoxaparin and dalteparin, although fondaparinux is chemically and functionally related by directly acting on factor 10-A. These drugs do not require routine laboratory monitoring, so they are used both in the outpatient setting and inside the hospital to treat and prevent blood clots. Importantly, low molecular weight heparins are preferred for anticoagulation in pregnant women.

Key Points

• Low Molecular Weight Heparins (LMWH)
  • Drug Names
    • Enoxaparin
    • Dalteparin
    • Fondaparinux
      • not technically part of the LMWH class, its mechanism of action is the same
  • Mechanism
    • Binds to and activates antithrombin III
      • Primarily inhibits factor Xa
      • Chemical structure of the complex causes LMWH to act selectively on factor Xa, not thrombin (in contrast to unfractionated heparin)
    • Does not require routine lab monitoring
      • Less monitoring makes LMWH preferred as an outpatient medication
      • Administered subcutaneously with longer half-life (2-4 hours) than unfractionated heparin (1-2 hours)
      • Better bioavailability than unfractionated heparin; renally excreted
  • Clinical Use
    • Anticoagulation
      • Pregnancy
        • First-line drug for anticoagulation in pregnancy due to ease of use
        • Heparins do not cross the placenta (low risk of teratogenicity and fetal hemorrhage)
      • Clot prevention
        • e.g. DVT/PE prophylaxis in hospitalized patients, cancer patients, outpatients at risk of DVT/PE
      • Less commonly used for acute coronary syndrome (ACS)
        • Less commonly used here than IV unfractionated heparin due to slower onset
      • In general:
        • IV unfractionated heparin is acute, rapid-acting anticoagulant for hospital use only (needs monitoring)
        • In contrast, subcutaneous LMWH is slower-acting, easier to use in outpatient setting (no monitoring needed)
  • Adverse Effects
    • Bleeding
      • Obvious side effect seen with all anticoagulants
    • Lower risk of heparin-induced-thrombocytopenia
  • Reversal
    • More difficult to reverse than unfractionated heparin, as protamine sulfate has less effect