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  • 1920

    Discovery of vitamin K10,11

    Dam and co-workers observed an acquired bleeding syndrome in chicken fed with a fat-free diet. They postulated the existence of a nutritional factor needed for normal hemostasis & called it vitamin K (K for Koagulation).

  • 1921

    Discovery of Coumarin Anticoagulants10,12

    An epidemic of a serious hemorrhagic diathesis of cattle was reported in North Dakota, USA.

  • 1924

    Discovery of Coumarin Anticoagulants10,12

    Frank Schofield found that cattle bled only when they were fed mouldy sweet clover. The hemorrhagic disease 'sweet clover disease', became manifested within 15 days of ingestion and killed the animal within 30–50 days. The disease could be reversed if the mouldy hay was removed or if fresh blood was transfused.

  • 1930

    Discovery of Coumarin Anticoagulants10,12

    Within 10 years, Edward Doisy elucidated the chemical structure of vitamin K and its method of synthesis was reported.

  • 1940

    Discovery of Coumarin Anticoagulants10,12

    Karl Link identified the active principle that caused the sweet clover disease –coumarins (3,3’-methylene-bis[4-hydroxycoumarin]).

    The natural coumarin was found to get oxidized in mouldy hay, to form the substance that later became better known as dicoumarol.

  • 1941

    Discovery of Coumarin Anticoagulants10,12

    The Mayo Clinic, reported the success of the use of dicoumarol in the prophylaxis of deep vein thrombosis after surgery.

  • 1943

    Discovery of Coumarin Anticoagulants10,12

    Henrik Dam & Edward Doisy won the Nobel Prize for their contributions to the understanding of blood clotting, especially the role of vitamin K.

  • 1945

    From Test Tube to Rat Poison12,4

    Karl Link proposed the use of dicoumarol as a rodenticide as the rodents would die from internal hemorrhage.

  • 1948

    From Test Tube to Rat Poison12,4

    Further research led to the development of warfarin, which was promoted as a rat Poison.

  • 1953

    From Rat Poison to Clinical Use12,4

    The development of “Nicoumalone” (acenocoumarol) by Stoll and Litvan (Ciba Geigy).

  • 1955

    From Rat Poison to Clinical Use12,4

    President of the U.S.A., Eisenhower received warfarin following a myocardial infarction.

  • 1956

    Towards the Development of a Perfect Anticoagulant–Acenocoumarol13,3

    Acenocoumarol came into clinical use in Europe and U.S.A.

    Acenocoumarol is reported to be a nearly ideal anticoagulant than any other commonly used coumarin or indanedione derivatives.