History of heparin.

The history of heparin is described from its initial discovery in 1916 to recent developments in knowledge of its mechanism of action and clinical use. Commercial production started soon after its discovery, in the 1920s, and improved purification methods led to animal studies and the first clinical trials in the 1930s. Research into heparin's chemical structure proved difficult, with uncertainty about the uronic acid moiety and the N-acetyl content, but the structure of the basic disaccharide unit was established by the 1960s, though knowledge of the heterogeneity and fine structure of heparin chains continued to accumulate over the next 20 years. In 1976, it was found that only one third of heparin chains bound with high affinity to antithrombin, and subsequent studies identified a unique pentasaccharide sequence, which was essential for antithrombin binding and anticoagulant activity - this pentasaccharide was synthesised in 1983. Clinical usage of heparin continued to increase and two major developments were the use of low- dose heparin for prevention of deep vein thrombosis and pulmonary embolism, and the development of low-molecular-weight heparin as a separate drug.