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Class

Anticoagulant

Pharmacodynamics
  • Indirect thrombin inhibitor that acts as a co-factor for the antithrombin-protease reaction:
    • Antithrombin III (ATIII) normally inhibits clotting factor proteases, especially IIa (thrombin), IXa, and Xa, by forming equimolar stable complexes with them
    • Heparin binds to and causes a conformational change of ATIII, exposing its active site for more rapid interaction with proteases and accelerating inhibition reactions 1000-fold
  • Requires the presence of ATIII
  • Acts as a co-factor without being consumed
Pharmacokinetics
  • Hepatic metabolism
  • Half-life 1.5 hours
  • Renal clearance
Clinical uses
  • Different methods of administration:
    • IV or SC
    • Continuous (following bolus) or intermittent
    • Therapeutic or prophylactic
    • Close monitoring of aPTT is necessary in patients receiving UFH infusions
  • Reversal:
    • Cease drug
    • Administration of antagonist protamine sulfate
    • For every 100 units of heparin remaining in patient, administer 1mg protamine IV
    • Excess protamine must be avoided as it also has an anticoagulant effect
Adverse effects
  • Heparin Induced Thrombocytopenia (see below)
  • Bleeding (risk increased in elderly women and renal failure)
  • Alopecia
  • Release of lipoprotein lipase from tissues, accelerating clearing of post-prandial lipaemia
  • Drug interactions:
    • Warfarin: increased INR due to changes in pharmacodynamics of warfarin
  • Long-term:
    • Osteoporosis
    • Mineralocorticoid deficiency
Precautions/contraindications
  • Severe hypertension
  • Advanced hepatic or renal disease
Heparin Induced Thrombocytopenia
  • 1-5% of patients receiving heparin
  • Can still occur with LMWH use
  • Type I:
    • Rapidly after drug administration
    • Due to direct platelet-aggregating effect of heparin
    • Little clinical significance, self-resolves
  • Type II:
    • Less common
    • 5-14 days after treatment
    • Due to auto-antibodies against complex of heparin and platelet factor 4. This activates platelets and causes thrombi, even in the setting of thrombocytopaenia
Further Reading

Pharmacology 101

Top 200 drugs

Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Co-creator of the LITFL ECG Library. Twitter: @rob_buttner

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