Heparin is a lipid substance isolated from the liver by Howell in 1918. He named it ‘heparin’. However, in 1922, he applied this name to a newly discovered substance; since then, ‘heparin’ has referred to a water-soluble complex carbohydrate that requires a plasma cofactor to exert its activity. The substance now bearing this name first appeared around 1922. In 1928, Howell analysed it as a sulphur-containing polysaccharide. Charles and Best further characterised it as a highly sulphated complex of glucuronic acid and glucosamine. The main early chemical research came from Jorpes, who discovered that heparin consists of glucuronic acid and hexosamine in a 1:1 ratio, with a sulphur content of 40 per cent by weight in the ash. He later discovered that the hexosamine was glucosamine. In 1976, research by Rosenberg showed that, in a mixture of heparin and antithrombin, approximately one-third of the heparin molecules were bound to protein and could be separated from the unbound molecules using a sucrose gradient. In the same year, in the laboratories of Lindahl and Barrowcliffe, it was discovered that on a chromatography column immobilised with antithrombin, heparin could be separated into two fractions: high-affinity and low-affinity. These three studies all indicated that in unfractionated heparin (UFH), only one in every three molecules binds tightly to antithrombin.