Heparin is one of the oldest medicines in use; discovered in 1916 at John Hopkins University by McLean and Howell and subsequently developed into a drug for clinical trials in the 1930s. It is now by far the most commonly used anticoagulant medicine with an extensive range of clinical applications.
Heparin is a highly sulphated glycosaminoglycan that inhibits blood coagulation. Blood clots form in response to trauma via a cascade of enzymes where a newly activated enzyme converts the next inactive enzyme into its active form. The coagulation cascade enables a rapid and greatly amplified response to tissue damage.
Antithrombin (AT) is an enzyme inhibitor that interrupts the coagulation cascade and so halts clotting by deactivating the enzymes IIa and Xa converting them back to their inactive form.
Heparin works by binding to (via a specific pentasaccharide sequence) and changing the structure of antithrombin. This change in conformation of the AT protein accelerates the rate of enzyme inhibition by AT by about 1,000 fold.