Warfarin

Warfarin is an anticoagulant medication that can be given orally. It works by decreasing levels of activity vitamin K in the blood. Vitamin K is necessary for the synthesis of many coagulation factors, and by blocking their production, coagulation slows down.

Warfarin is a derivative of coumarin, a plant chemical found in low levels in licorice, lavender and various other species. As well as its use as an anticoagulant, warfarin-like compounds are used as rat poison.

Warfarin is slower acting than another common anticoagulant heparin, though it has a number of advantages. Heparin must be given by injection, so this cannot be done by the patient. Warfarin has a long half-life and needs only be given once a day. As well as these problems, heparin can also cause thrombocytopenia (a decrease in platelets), which may cause bleeding. For these main reasons, hospitalised patients are usually given heparin initially, and are then moved on to warfarin.

Warfarin, too, does have side effects. It has a very narrow therapeutic range, which means the levels in the blood that are effective are close to the levels that cause bleeding. This means it is easy to over- or under-coagulate the patient. Warfarin's effects must be closely monitored, this is done by using the INR.

There are many drug-drug interactions with warfarin, and its metabolism varies greatly between patients. This makes finding the correct dosage difficult.

Warfarin cannot be given to pregnant women, especially in the first trimester, as it is a teratogen.

If an overdose of warfarin is made, the effects can be reverse by giving a vitamin K injection, or if necessary fresh frozen plasma infusion to replace coagulation proteins.

Warfarin is given to people with a thrombosis tendency. This can prevent growth or embolism of a thrombus.

The early 1920's saw the outbreak of a previously unrecognized disease of cattle in the northern United States and Canada. Cattle would die of uncontrollable bleeding from very minor injuries, or sometimes drop dead of internal hemorrhage with no external signs of injury. In 1922, Frank Schofield, a Canadian veternarian, determined that the cattle were ingesting a toxin from moldy silage made from sweet clover that functioned as a potent anticoagulant.

The identity of the anticoagulant substance in moldy sweet clover remained a mystery until 1940 when Karl Link and Harold Campbell, chemists working at the University of Wisconsin, determined that it was the coumarin derivative 4-hydroxycoumarin. Over the next few years, numerous similar chemicals were found to have the same anticoagulant properties. The first of these to be widely commericialized was dicoumarol, patented in 1941. Link continued working on developing more potent coumarin-based anticoagulants for use as rodent poisons, resulting in warfarin in 1948. (The name warfarin stems from the acronym WARF, for Wisconsin Alumni Research Foundation.)

After an incident in 1951 where a naval enlisted man unsuccessfully attempted suicide with warfarin and recovered fully, studies began in the use of warfarin as a therapeutic anticoagulant. It was found to be generally superior to dicoumarol, and in 1954 was approved for medical use in humans.