Heparin
| 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. |
Warfarin
| 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. |
Fondaparinux
| 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. |
"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.
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