Property Warfarin Heparin Enoxaparin
Uses AF, DVT/PE, Prosthetic Valves AF, DVT/PE, Extra-corporeal Circuit Anticoagulation DVT Prophylaxis
Pharmaceutics Marevan and coumadin may potentially have different bioavailabilities (it has not been assessed) and so should not be substituted Mucopolysaccharide organic acid which occurs naturally in the liver and in mast cells, with a highly variable molecular weight (between 5,000 and 25,000 Da) Smaller fragments of heparin (prepared from UFH), with a mean molecular weight of 5,000 Da
Mechanism of Action Prevents the return of vitamin K to its reduced form, and therefore the gamma-carboxylation of vitamin-K dependent clotting factors (II, VII, IX, X), as well as Protein C and Protein S). Potentiates the effect of ATIII, rapidly increasing its anti-IIa and anti-Xa effect (1:1 effect).

In higher concentrations also inhibits IXa, XIa, XIIa, and platelet aggregation.
Potentiates the action of ATIII, increasing inhibition of Xa and IIa, but (unlike UFH) in a 4:1 ratio.

More predictable effect on Xa standardises dosing and justifies lack of monitoring requirement.
Onset 8-12 hours. Peak at 72 hours due to the half-life of existing clotting factors, and the total body stores of vitamin K Immediate IV onset
Absorption 100% bioavailability IV, SC SC only
Distribution 99% protein bound Low lipid solubility, highly protein bound Does not bind to heparin-binding proteins
Metabolism Complete hepatic metabolism. Significant pharmacokinetic interaction with enzyme inducers and inhibitors. Hepatic interactions due to enzymatic induction (ETOH, amiodarone, salicylates, NSAIDs) and inhibition (OCP, barbiturates, carbamazepine) Renal elimination of metabolites
Elimination Faecal and renal elimination of metabolites, t1/2β of 40 hours Renal of inactive metabolites Renal of active drug and inactive metabolites
CVS Microthrombi Hypotension with rapid IV administration
Metabolic Less osteoporosis due to less protein (and therefore tissue) binding Osteoporosis
Renal Inhibits aldosterone secretion
Haeme Haemorrhage Haemorrhage, HITTs Haemorrhage, lower risk of HITTs than UFH. Less thrombocytopaenia.
Immune Hypersensitivity reactions
Reversal - Waiting
- Vitamin K
- Prothrombinex
Reversed with protamine (1mg per 100U). Incomplete reversal with protamine as only the anti-IIa effect is inhibited.
Other Teratogenic. Complicated pharmacokinetics requiring monitoring using INR. Requires monitoring with APTT or ATIII levels. Large interpatient variability due to variable amounts of ATIII.

1 unit is the amount of heparin required to prvent 1ml of blood clotting for 24 hours at 0°C
No monitoring required.


Heparin-Induced Thrombotic Thrombocytopenia comes in two flavours:

  • Type I:
    • Is non-immune mediated
    • Occurs within 4 days of anticoagulant doses
    • Is an isolated thrombocytopenia without clinical significance
  • Type II:
    • Is immune mediated
    • Occurs within 4-14 days
    • Is associated with serious thrombosis and high mortality (typically from PE) and morbidity (from CVA and limb ischaemia)


Protamine is:

  • A basic cationic protein derived from salmon sperm which combines with the acidic anionic heparin to form a stable, inactive salt in solution
  • Cleared more rapidly than heparin
    Rebound anticoagulation may occur.

Adverse effects from protamine include:

  • Histamine release
    • Bronchospasm
    • Hypotension
  • Pulmonary hypertension
    This can be profound and result in a dramatic increase in RV afterload and EDV, with a corresponding fall in LV preload (interventricular interdependence), leading to dramatic hypotension and arrest.
    • Mediated by thromboxanes
    • Due to protamine-heparin complexes, rather than protamine alone
      Administration of protamine in absence of heparin does not lead to pulmonary hypertension.
  • Anticoagulation
    When given in excess.


  1. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
  2. Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
  3. ANZCA August/September 2011
  4. Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.
Last updated 2019-07-18

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