Oral Anticoagulants

HISTORY OF ORAL ANTICOAGULATION The discovery of oral medications to control thrombotic disorders in humans probably started with a report in 1922 by U.S. veterinarian Frank W Schofield. Dr Schofield reported a bleeding diathesis in cattle that simulated hemorrhagic septicemia and “black leg syndrome”. He hypothesized that this disorder was due to feeding spoiled sweet clover to the cattle.¹

In 1935, while studying the sterol metabolism of chicks in Copenhagen, 1943 Nobel Prize winner Henrik Dam discovered a bleeding tendency in the chicks fed a diet deficient in lipids. These results suggested the chicks lacked a substance necessary for normal coagulation; “Koagulations-Vitamin” or vitamin K. He studied this vitamin further with respect to its occurrence and biological function in animals and plants as well as its application in human medicine.²

In 1933 a Wisconsin farmer arrived at Karl Paul Link's laboratory at the University of Wisconsin-Madison with a pail of blood that would not coagulate. He also brought a small heap of spoiled sweet clover and a dead heifer in the back of his truck. Isolation and purification of the hemorrhagic compound led to the discovery of dicumarol (3,3-methylene-bis- {4-hyroxycoumarin}).³ Clinical studies were immediately started on this compound, establishing the basis for rodenticides and the first oral anticoagulant. The compound greatly diminished prothrombin activity and delayed the clotting mechanism in blood. The first prophylactic and therapeutic effects and the drug's mechanism in influencing deep vein thrombosis were described in 1942.^4-6 Link, in 1948, went to the director of the Wisconsin…

ABBREVIATIONS: AMS = anticoagulation management service; DVT = deep vein thrombosis; GLA = gamma-carboxyl glutamic acid; GLU = glutamic acid; INR = international normalized ratio; IRP = international reference plasma; ISI = international sensitivity index; OAT = oral anticoagulant therapy; POC = point-of-care device; PT = prothrombin time; VTE = venous thromboembolism; WHO = World Health Organization.