In contrast, to catalyze factor Xa inhibition by AT, heparin needs only to bind to AT.14 In both cases binding occurs at the unique pentasaccharide sequence found within some heparin molecules. Heparin chains consisting of ,18 saccharide units are too short to bridge AT to thrombin. Consequently, these chains are unable to catalyze thrombin inhibition. However, short heparin chains can catalyze inhibition of factor Xa by AT.15-18 By inactivating thrombin or attenuating its genera- tion, heparin not only prevents brin formation but also inhibits thrombin-induced activation of platelets and factors V, VIII, and XI.19-21 The interaction of heparin with HCII is charge dependent, but pentasaccharide independent. Catalysis In 1968, Abildgaard identi ed this cofactor as anti- thrombin III,3 which is now referred to as anti- thrombin. The major anticoagulant action of heparin is mediated by the heparin/AT interaction. The mech- anism of this interaction was demonstrated in the 1970s.4-6 Heparin binds to positively charged residues on AT, producing a conformational change at the AT arginine reactive center that converts AT from a slow to a rapid inhibitor of serine proteases. The arginine reactive center on AT binds covalently to the active center serine of thrombin and other coagulation enzymes, thereby irreversibly inhibiting their proco- agulant activity.5 Heparin then dissociates from AT and is reused (Fig 1).7 1.1.1 Structure and Mechanism of Action: Heparin is a highly sulfated mucopolysaccharide. It is hetero- geneous with respect to molecular size, anticoagulant activity, and pharmacokinetic properties (Table 1). 