|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.|
- Vitamin K
|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)
- 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
- 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.
When given in excess.
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
- Smith S, Scarth E, Sasada M. Drugs in Anaesthesia and Intensive Care. 4th Ed. Oxford University Press. 2011.
- ANZCA August/September 2011
- Petkov V. Essential Pharmacology For The ANZCA Primary Examination. Vesselin Petkov. 2012.