An early recipient of warfarin was US President Dwight Eisenhower, who was prescribed the drug after having a heart attack in 1955.The exact mechanism of action remained unknown until it was demonstrated, in 1978, that warfarin inhibits the enzyme vitamin K epoxide reductase, and hence interferes with vitamin K metabolism.Lavrenty Beria and I. V. Khrustalyov are thought to have conspired to use warfarin to poison Soviet leader Joseph Stalin. Warfarin is tasteless and colourless, and produces symptoms similar to those that Stalin exhibited. Pest control
Rodents
Coumarins (4-hydroxycoumarin derivatives) are used as rodenticides for controlling rats and mice in residential, industrial, and agricultural areas. Warfarin is both odorless and tasteless, and is effective when mixed with food bait, because the rodents will return to the bait and continue to feed over a period of days until a lethal dose is accumulated (considered to be 1 mg/kg/day over about six days). It may also be mixed with talc and used as a tracking powder, which accumulates on the animals skin and fur, and is subsequently consumed during grooming. The LD50 for warfarin is 50–100 mg/kg for a single dose, after 5–7 days. LD50 1 mg/kg for repeated daily doses for 5 days, after 5–8 days. The IDLH value is 100 mg/m3 (warfarin; various species).The use of warfarin itself as a rat poison is now declining, because many rat populations have developed resistance to it, and poisons of considerably greater potency are now available. Resistance is due to an autosomal dominant on chromosome 1 in Norway rats.
Embolization
A thrombus may become detached and enter circulation as an embolus, finally lodging in and completely obstructing a blood vessel, which unless treated very quickly will lead to tissue necrosis (an infarction) in the area past the occlusion. Venous thrombosis can lead to pulmonary embolism when the migrated embolus becomes lodged in the lung. In people with a "shunt" (a connection between the pulmonary and systemic circulation), either in the heart or in the lung, a venous clot can also end up in the arteries and cause arterial embolism.Arterial embolism can lead to obstruction of blood flow through the blood vessel that is obstructed by it, and a lack of oxygen and nutrients (ischemia) of the downstream tissue. The tissue can become irreversibly damaged, a process known as necrosis. This can affect any organ; for instance, arterial embolism of the brain is one of the causes of stroke. Prevention
The use of heparin following surgery is common if there are no issues with bleeding. Generally, a risk-benefit analysis is required, as all anticoagulants lead to an increased risk of bleeding. In people admitted to hospital, thrombosis is a major cause for complications and occasionally death. In the UK, for instance, the Parliamentary Health Select Committee heard in 2005 that the annual rate of death due to thrombosis was 25,000, with at least 50% of these being hospital-acquired. Hence thromboprophylaxis (prevention of thrombosis) is increasingly emphasized.