Warfarin: From Moldy Sweet Clover Cattle Deaths to Eisenhower's Heart

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In the early 1920s, cattle across the northern United States and Canada began bleeding to death after minor procedures, with 21 of 22 cows dying after dehorning on one farm. This episode follows the chemical behind it. In 1921 Canadian veterinary pathologist Frank Schofield traced the deaths to moldy sweet clover silage, and in 1929 Lee M. Roderick showed it destroyed prothrombin. Between 1933 and 1940 Karl Paul Link's team at the University of Wisconsin isolated dicoumarol, formed when fungi metabolize the sweet smelling plant compound coumarin, and by 1948 they had developed warfarin, named for the Wisconsin Alumni Research Foundation, as a rat poison.

In 1951 a US Navy inductee survived several days of warfarin doses after treatment with vitamin K, opening the door to human trials. The FDA approved it in 1954, and in 1955 it treated President Dwight D. Eisenhower after his heart attack. The episode explains why it is not a true blood thinner but a blocker of the VKORC1 enzyme that recycles vitamin K, and why diet, antibiotics and genetics make dosing a narrow balancing act.

An unverified rumor that Lavrentiy Beria used warfarin against Joseph Stalin
INR monitoring and eating the same amount of leafy greens every day
Warfarin necrosis, protein C, and bridging with heparin in the first days
Purple toe syndrome and fetal warfarin syndrome
Resistant rats, bioaccumulating superwarfarins, and poison gel spread through vampire bat grooming

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