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Milestones in Anticoagulant Drugs

An article on antithrombotic therapy by Jack Hirsh, MD, and these accompanying milestones were published in December 2008 as part of the special ASH anniversary brochure, 50 Years in Hematology: Research That Revolutionized Patient Care.


1916 Heparin is discovered in dog liver by a team from The Johns Hopkins University in Baltimore, MD.
1930s Scientists purify heparin and produce enough pure material for clinical use.
1932 A U.S. clinical scientist shows that heparin requires a plasma factor (now known as antithrombin or AT) for its anticoagulant action.
1970s The mechanism of the interaction between heparin and AT is explained by scientists from Harvard University and from the University of Uppsala.


1920s Cattle in the northern U.S. and Canada are dying from a bleeding disease caused by a substance in moldy sweet clover.
1930s A Danish scientist discovers that dietary vitamin K is necessary to prevent bleeding.
1939 Researchers at the University of Wisconsin identify the substance in moldy clover as dicumarol. Over the next several years, warfarin, a related compound, is made in this laboratory.
1941 Dicumarol is first given to patients at the Mayo Clinic.
1950s Clinical studies with warfarin begin in the U.S., and the drug is approved for clinical use in 1954.
1970s The mechanism of action of vitamin K is explained by scientists who discover that warfarin's anticoagulant effect is caused by interference with the action of vitamin K.

Low-Molecular-Weight Heparin (LMWH)

1970s Researchers begin work on LMWH.
1980s The first clinical studies of LMWH are performed in the mid-1980s and show that LMWH is effective for preventing venous thrombosis in high-risk patients.
1990s LMWH can now be administered safely in an out-of-hospital setting.


1979 Scientists determine the structure of the high-affinity binding site on heparin and soon after demonstrate that this high-affinity site is a pentasaccharide (five-sugar unit) with a unique structure.
1980s The pentasaccharide is synthesized, and, over the ensuing two decades, the synthetic compound is developed into a drug for clinical use.
2000s Multicenter clinical trials show that fondaparinux is an effective antithrombotic drug.