Blood Coagulation
Mechanism of Action
Side Effects
The Future


The discovery of warfarin was centered in Canada and the United States1. In the early part of the 20th century, farmers in the northern prairie states of Canada and the USA began planting sweet clover plants imported from Europe. Although the sweet clover proved to be nutritious when used as fodder, it also brought a fatal disease which decimated cattle herds and horrified farmers: sweet clover disease, in which affected cattle developed relentless, spontaneous bleeding. Schofield, a veterinary pathologist in Alberta, reported in 1921 that the disease was caused by consumption of spoilt sweet clover hay. The fresh plant was known to contain the compound coumarin, which was not pathogenic. The mystery of why spoilt hay caused the disease was solved by Karl Paul Link and his co-workers in 1940 : in mouldy hay, coumarin is oxidised to 4-hydroxycoumarin and then coupled with formaldehyde and another coumarin moiety to form dicoumarol, an anticoagulant. This was responsible for the disease. Dicoumarol was patented in 1941 and was therapeutically used as an anticoagulant.


Renewed impetus to the development of oral anticoagulants came again from Link in 1946. Working on the problem of rodent control, he found that dicumarol was too weak and unreliable as a rodenticide. The most potent compound Link and co-workers discovered was 3-(2-acetyl-1-phenylethyl)-4-hydroxycoumarin. Patent rights were assigned to Link's research benefactors, the Wisconsin Alumni Research Foundation, from which the name warfarin was derived. In 1948, warfarin was launched as the ideal rat poison.


In 1951, a  navy recruit unsuccessfully attempted suicide with 567 mg of warfarin. His surprising full recovery induced research into the anticoagulant potency of warfarin in humans. It was found to be far superior to dicoumarol. Clinicians quickly discarded dicoumarol in favour of "rat poison" warfarin : it was introduced commercially in 1954. In that same year, President Eisenhower was treated with warfarin following a heart attack.

Today, warfarin is the standard treatment  for long term oral anticoagulant therapy.

karl link

Karl Paul Gerhardt Link (1901-1978)