Heparin

Summary

Heparin is an anticoagulant drug used to prevent blood clotting in a variety of different clinical contexts. Heparin works by activating antithrombin, which then goes on to inhibit several clotting factors. Namely, the activated forms of factors 2 and 10 are inhibited. This leads to anticoagulation, which is measured or monitored by an elevation of PTT.  In contrast to other anticoagulants, Heparin is considered to be safe to use during pregnancy. Potential side effects of heparin include excessive bleeding, and Heparin Induced Thrombocytopenia, or HIT. In HIT, antibodies are produced against a heparin-platelet-factor four complex. This activates platelets, causing a pro-thrombotic state that consumes or uses up platelets while reducing platelet counts. Importantly, heparin’s effects can be reversed by administering protamine sulfate.

Key Points

• Heparin
  • Also known as unfractionated heparin or UFH
  • Mechanism
    • Activates antithrombin III
      • Antithrombin III then works to inactivate both factors IIa (thrombin) and Xa
    • Usually administered subcutaneous or IV
      • Rapid onset; immediate if given IV
      • Short half-life (1-2 hours)
  • Clinical Use
    • Anticoagulation
      • Often used in hospital setting due to its rapid onset
      • Part of immediate management plan for ACS along with dual antiplatelet therapy (aspirin, ADP receptor blocker)
      • Safe for pregnancy
        • Does not cross placenta
        • Note: LMWH are preferred here due to ease of use
    • Used as a “heparin bridge” when initiating treatment with warfarin
      • Due to risk of warfarin-induced skin necrosis during initial prothrombotic window
  • Laboratory Findings
    • Increased PTT
      • Activated partial thromboplastin time (aPTT or PTT) is used to monitor the therapeutic effect of unfractionated heparin
        • Measures inhibition of intrinsic coagulation cascade, by adding an intrinsic activator (silica, celite, kaolin, ellagic acid) and seeing how long it takes for blood to clot.
    • Also prolongs the thrombin time (TT)
      • Due to antithrombin’s role in directly inactivating thrombin
      • Thrombin time is measured by mixing fibrinogen with blood and measuring how long it takes to turn into fibrin
      • Note: not the same as prothrombin time
  • Adverse Effects
    • Bleeding
      • Dose-limiting side effect of all anticoagulants
    • Heparin-induced thrombocytopenia (HIT)
      •   IgG develops against platelet factor-4/heparin complex
        • Activates platelets causing mixed picture of thrombocytopenia with thrombosis
        • Treat with DTIs (argatroban, -rudins)
    • Osteoporosis (rare)
    • Type 4 RTA
      • Suppresses aldosterone production
  • Reversal
    • Protamine sulfate
      • Protamine sulfate binds to heparin, causing chemical inactivation
    • In contrast to warfarin, Fresh frozen plasma (FFP) is not useful for heparin reversal as it contains antithrombin III, which can further increase the effects of heparin.