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.
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.