Effect of low molecular weight heparin preparations on the inhibition of thrombin by heparin cofactor II.

1. Heparin molecules approximately 24 to 30 residues in length are required to catalyze the thrombin-HC II reaction. The requirement for heparin molecules of this length is consistent with a model for catalysis in which heparin binds HC II and thrombin simultaneously to form a ternary complex in a manner similar to that proposed for the thrombin-AT III reaction. Smaller molecules (18 or more monosaccharide units in length) are required to catalyze the thrombin-AT III reaction. 2. The specific AT III-binding pentasaccharide containing 3-O-sulfated glucosamine is not required for activity with HC II. 3. Some low molecular weight heparin preparations have significant activity with HC II (approximately 10 to 20% that of standard heparin). This is probably related to the presence of species with molecular weights greater than 6000 to 7500 (24 to 30 monosaccharide units) in these preparations.