It is hetero- geneous with respect to molecular size, anticoagulant activity, and pharmacokinetic properties (Table 1). Heparin molecules range in molecular weight from 3,000 to 30,000 kDa with a mean of 15,000, which corresponds to approximately 45 saccharide units (Fig 2).8-10 Only about one-third of the heparin mole- cules possess the unique pentasaccharide sequence and it is this fraction that is responsible for most of the anticoagulant effect of heparin.8,11 Heparin chains that lack the pentasaccharide sequence have minimal anticoagulant activity when heparin is given in thera- peutic concentrations. However, at concentrations higher than those usually administered clinically, heparin chains with or without the pentasaccharide sequence can catalyze thrombin inhibition by hep- arin cofactor II (HCII), a second plasma cofactor.12 Figure 1. Inactivation of clotting enzymes by heparin. Top, ATIII is a slow inhibitor without heparin. Middle, Heparin binds to ATIII through a high-af nity pentasaccharide and induces a con- formational change in ATIII, thereby converting ATIII from a slow inhibitor to a very rapid inhibitor. Bottom, ATIII binds cova- lently to the clotting enzyme, and the heparin dissociates from the complex and can be reused. AT5antithrombin. (Reprinted with permission from Hirsh et al.7) Table 1 Molecular Size, Anticoagulant Activity, and Pharmacokinetic Properties of Heparin Attribute Characteristics Molecular size Mean molecular weight, 15,000 kDa Anticoagulant activity Only one-third of heparin molecules contain the high-af nity pentasaccharide required for anticoagulant activity Clearance High-molecular-weight moieties are cleared more rapidly than lower-molecular-weight moieties Revision accepted August 31, 2011. Af liations: From the University of New Mexico (Dr Garcia), Albuquerque, NM; the Cambridge University Hospitals NHS Trust (Dr Baglin), Addenbrooke s Hospital, Cambridge, England; the Thrombosis and Atherosclerosis Research Institute and McMaster University (Dr Weitz), Hamilton, ON, Canada; and the Hotel Dieu University Hospital (Dr Samama), Place du Parvis Notre Dame, Paris, France. 