#MedicalHistoryMondays
Today we’ll talk about Warfarin!
The year is 1920.
Farmers across North America & Canada notice that their cattle 🐮 are haemorrhaging after minor procedures & sometimes spontaneously, causing them to bleed to death. (cont’d)
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Today we’ll talk about Warfarin!
The year is 1920.
Farmers across North America & Canada notice that their cattle 🐮 are haemorrhaging after minor procedures & sometimes spontaneously, causing them to bleed to death. (cont’d)
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1921: Frank Schofield, a Canadian veterinary pathologist, determines that the cattle were ingesting moldy hay made from sweet clover. Only spoiled hay made from sweet clover (grown exclusively in North America) produced the disease . (cont’d)
Schofield separated good clover stalks and moldy clover stalks from the same hay mow, and fed each to a different rabbit 🐰.
The rabbits that ingested the bad stalks died from hemorrhagic illness. The other rabbits remained well . (cont’d)
The rabbits that ingested the bad stalks died from hemorrhagic illness. The other rabbits remained well . (cont’d)
In 1929, North Dakota veterinarian Lee M Roderick demonstrated that the condition was due to a lack of functioning prothrombin.
The identity of the anticoagulant substance in spoiled sweet clover running a mystery until 1940.
(cont’d)
The identity of the anticoagulant substance in spoiled sweet clover running a mystery until 1940.
(cont’d)
In 1933, Karl Paul Link working at the University of Wisconsin set out to isolate and characterized the hemorrhagic agent from the spoiled hay.
It took five years before Link’s student Harold A. Campbell recovered 6 mg of crystalline anticoagulant.
(cont’d)
It took five years before Link’s student Harold A. Campbell recovered 6 mg of crystalline anticoagulant.
(cont’d)
Next, Mark A. Stahmann took over the project and initiated a large-scale extraction and through degradation experiments established that the anticoagulant was 3, 3’-methylenebis-(4-hydroxycoumarin)...
... which they later named Dicoumarol.
... which they later named Dicoumarol.
Dicoumarol was a product of the plant molecule coumarin ( not to be confused with Coumadin, warfarin’s tradename).
Coumarin is now known to be present in many plants, and produces the notably sweet smell of freshly cut grass or hay.
Coumarin is now known to be present in many plants, and produces the notably sweet smell of freshly cut grass or hay.
The 1st drug to be commercialized was dicoumarol, patented in 1941.
Karl Link continued working on 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.
Karl Link continued working on 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 in Army inductee attempted suicide with multiple doses of warfarin but recovered fully after presenting to Naval hospital and being treated with vitamin K, studies began in the use of warfarin as a therapeutic anticoagulant.
In 1954, warfarin was approved for medical use in humans.
An early recipient of warfarin was US President Dwight Eisenhower, who was prescribed the drug after having a heart attack in 1955.
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 1978, when it was shown that warfarin inhibits the enzyme epoxide reductase and hence interferes with vitamin K metabolism.
The rest is history!
This wraps up our #first Medical History Monday!
Thank you for reading!
The rest is history!
This wraps up our #first Medical History Monday!
Thank you for reading!
