title: Heparin to pentasaccharide and beyond: the end is not in sight.
abstract: The 87-year history of heparin began in 1916 when a 26-year-old medical student named Jay McLean startled his mentor William Howell, Professor of Physiology at Johns Hopkins University, by proclaiming that he had discovered "antithrombin." This discovery was so surprising to Howell because he had expected McLean to isolate thromboplastin, a clot-promoting substance from animal tissue. In 1928, Charles Best, M.D., in Toronto, Canada, organized a team of chemists, physiologists, and surgeons to focus on the development of heparin. This group determined which animal tissues were the best source, had performed purification and identification, and had determined pharmacologic properties in vitro. By 1935, they were ready for human trials. By 1941, the group reported a series of 700 patients treated with the glycosaminoglycan called heparin. Meanwhile a critical cofactor, antithrombin, had been discovered at the University of Iowa (Brinkhous, et al). Introduction of newer tests for laboratory monitoring enabled refinement of dosages during the 1960s and 1970s. Its use permitted the development of hemodialysis and cardiopulmonary bypass surgery, and the prophylaxis of deep vein thrombosis in surgical patients. The concept of low-molecular-weight heparin occurred to Dr. Choay and others in France in the late 1970s. During the 1980s and 1990s, the development of low-molecular-weight heparins evolved for both prophylaxis and therapy. The first synthetic product was called the pentasaccharide, named for the five critical sugar units in heparin that bind to antithrombin (1983). Since then, this drug has been studied extensively to prove its clinical efficacy and safety.
authors.affiliation: Loyola University Medical Center, Maywood, Illinois 60153, USA. hlmehd64@aol.com
authors.forename: Harry L
authors.initials: HL
authors.lastname: Messmore
authors.forename: William H
authors.initials: WH
authors.lastname: Wehrmacher
authors.forename: Erwin
authors.initials: E
authors.lastname: Coyne
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D006493:Heparin / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009844:Oligosaccharides / Q000266:history / Q000627:therapeutic use*; D013923:Thromboembolism / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D006495:Heparin, Low-Molecular-Weight; D009844:Oligosaccharides; C049714:IC 831423; D006493:Heparin