ABSTRACT
Heparin Beginning with the first angioplasty procedure reported in humans, intravenously administered unfractionated heparin has been the mainstay of anti-thrombotic therapy during PCI. Heparin is a glycosaminoglycan composed of chains of alternating residues of D-glucosamine and uronic acid. Its major effect as an anticoagulant is provided by a unique pentasaccharide, found on only one-third of heparin molecules, with a highaffinity binding sequence to antithrombin (AT). The anticoagulant properties of heparin are mediated largely through its interaction with AT. heparin binding to AT causes a conformational change in the molecule, markedly accelerating its ability to inactivate the coagulation enzymes thrombin (factor IIa), factor Xa, and factor IXa. Of these enzymes, thrombin is the most sensitive to inhibition by heparin/AT. Heparin molecules containing fewer than 18 saccharides are unable to bind thrombin and AT simultaneously and hence are unable to accelerate the inactivation of thrombin by AT. These smaller heparin molecules do, however, retain their ability to catalyze the inhibition of factor Xa by AT. Heparin also possesses the ability to inactivate thrombin via a second plasma cofactor, heparin cofactor II. Inhibition of thrombin via this mechanism does not require the unique AT-binding pentasaccharide, but it does require much higher doses of heparin than those required to catalyze the activity of AT.
