Pharm 101: Heparin

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

Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU Emergency Medicine Trainee with interests in medical education, ECG interpretation, and the use of point-of-care ultrasound in the undifferentiated patient. Co-author of the LITFL ECG Library | Twitter

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