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
- Nickson C. Heparin Induced Thrombotic Thrombocytopaenia Syndrome
- Nickson C. Protamine
- Nickson C. VTE Prophylaxis
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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