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Heparin

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Summary

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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.