Coumarin derivative used widely for prophylaxis of systemic thromboembolism in patients with AF, prosthetic heart valves and in the treatment of DVT/PE.


Warfarin inhibits the synthesis of vitamin K dependant clotting factors (II, VII, IX and X).



Clotting factor precursors are produced in the liver and are activated by the gamma carboxylation of their glutamic acid residues. This process is linked to the oxidation of reduced vitamin K. Warfarin inhibits to action of vitamin K epoxide reductase, preventing the return of vitamin K to it’s reduced active state.

Warfarin doesn’t effect circulating factors that are already active so onset can take 72 hours. It can also inhibit the effect of protein C and protein S first, creating a prothrombotic state initially. In some patients this period of time will need to be covered with LMWH or unfractionated heparin.

Side effects

Teratogenicity – in particular during organogenesis in the first trimester, however in the third trimester warfarin can cross the placenta and cause foetal haemorrhage in particular intraventricular haemorrhage.
Drug interactions – metabolised by hepatic cytochrome P450 system, therefore any enzyme inhibitors or inducers will effect circulating levels of warfarin.


Vitamin K can take time to work as it will not be effective until new clotting factors are activated. Also in high doses (e.g. 10mg) it can prevent anticoagulation for a number of days.

More rapid reversal can be achieved with FFP or clotting factor concentrates e.g. Octaplex.


Completed absorbed from the gut and 95% protein bound. Hepatic metabolism and renal excretion.


Prothrombin time (PT) is a measure of extrinsic system (factor VII) activity, as well as common factors like factor X. This is converted into the INR which standardises the result for laboratory variations in PT measurement across the world.



Unfractionated heparin

3-30 kilodaltons

An anionic mucopolysaccharide organic acid containing many sulphate residues.

Used as a continuous intravenous infusion to treat DVT, PE and in critical arterial occlusion. May have a role in DIC.


Heparin potentiates antithrombin III, increasing the rate of formation of the the antithrombin-thrombin complex by 1000 fold. Factors XIIa, XIa and IXa also inhibited as dose increases.

Side effects

Haemorrhage is the most common due to a relative overdose.

Heparin Induced Thrombocytopaenia (HIT)

Non-immune mediated (type 1): Onset around four days post heparin, mild and self-limiting – recovers when heparin stopped. Unusual to have severe complications from this.

Immune mediated (type 2): Onset around four to fourteen days after administration. Much more severe than type 1, incidence around 1-5% with unfractionated heparin but less than 1% with low molecular weight heparins. Heparin and platelet complexes bound by IgG causing aggregation and occlusive symptoms. 50% of patients will get serious thrombotic events e.g. pulmonary embolus.

A good review of heparin induced thrombocytopaenia is available on Life in the Fast Lane.


Ineffective orally therefore given SC or IV.
Low lipid solubility – doesn’t cross placenta or blood brain barrier.
Negatively charged and highly protein bound.

Hepatic metabolism by heparinases – desulphated and excreted in the urine.


A basic protein originally isolated from salmon sperm, though now synthesised through recombinant biotechnology.

Given intravenously to reverse effects of unfractionated heparin.

It is a positively charged molecule that forms an inactive complex with heparin that is cleared by the reticuloendothelial system.

1mg of protamine will reverse 100  units of heparin.

Side effects

Hypotension, dyspnoea and flushing (mediated by histamine release)
Anaphylaxis in particular in individuals with fish allergy

Low molecular weight heparin (LMWH)

e.g. Dalteparin, enoxaparin

6-8kDa, formed from depolymerisation of heparin. More effective at inhibiting factor Xa and less effective at potentiating antithrombin-thrombin complex formation.

Can be given as a single daily dose with less need for monitoring. Less risk of HIT (<1%).


APTT (activated partial thromboplastin time) measures activity of intrinsic pathway factors (XII, XI, IX, VIII).

LMWH inhibit Xa and therefore will not effect APTT, need to measure activated factor X levels.

Anti-platelet drugs


Cyclo-oxygenase 1 inhibitor

Used to reduce the risk of unstable angina progressing to MI and reduces mortality following acute MI. Reduces risk of stroke for patients suffering from TIAs. May potentially reduce cardiovascular risk when taking daily in a low dose, though the benefits vs risks of this remain controversial.

Mechanism: Irreversibly inibits cyclo-oxygenase isoenzyme 1 within the platelet, reduced the production of thromboxane A2. This reduces platelet activation and aggregation.


Platelet phosphodiesterase inhibitor

May reduce stroke risk when combined with aspirin.

Mechanism: Inhibits phosphodiesterase in the platelet which normally breaks down cyclic AMP. This counteracts the effects of calcium on the glycoprotein IIb/IIIa receptor by limiting vesicular release of thromboxane A2 and other activating substances. This potentiates the effects of prostacyclin which works in a similar way by increasing the concentration of cyclic AMP.


Inhibition of ADP binding

Used to reduce risk of stent thrombosis following coronary artery intervention. It also reduces stroke risk in peripheral vascular disease.

Mechanism: Irreversibly prevents ADP from binding to it’s platelet receptor, therefore preventing glycoprotein IIb/IIIa receptor from transforming into it’s active form.

Tirofiban and Abciximab

Glycoprotein IIb/IIIa antagonists

Used concurrently with heparin around the time of acute coronary events.

Mechanism: Antagonises the glycoprotein IIb/IIIa receptor, limiting platelet activation and aggregation. It doesn’t effect the final common pathway or coagulation cascade.