Inhibition of bovine factor viii‐induced guinea pig platelet aggregation by simple sugars and derivatives

Abstract

Working with the hypothesis that the binding of carbohydrate groups is important in the induction of platelet aggregation by bovine factor VIII, we studied 36 different sugars and sugar derivatives for their ability t o inhibit the aggregation of guinea pig platelets. Concentrations that produced 5 0% inhibition of the aggregation response ranged from 232 mM (galactose) t o 12 mM (glucosamine and galactosamine).Using these values, we found that several factors affected the ability of sugar structures t o inhibit bovine factor VIII-induced aggregation of guinea pig platelets. In general, galactose and its derivatives were not as effective as glucose and its derivatives. Sugars possessing a-glycosidic linkages tended to be stronger inhibitors than those having &linkages. Polyols were better inhibitors than their corresponding aldoses. D-fucose (129 mM) was a weaker inhibitor than L-fucose (66 mM), but Dand L-arabinitol were not significantly different. N-acetylation of glucosamine reduced its ability t o inhibit aggregation. The number of free hydroxyl groups in a molecule did not appear t o be a significant determinant of its ability t o inhibit aggregation.The results support the hypothesis that a binding site for carbohydrate groups exists either on the platelet membrane or on the bovine factor VIII molecule. The binding of the carbohydrate t o this site is an important step in the induction of aggregation, and this binding site is relatively specific for the carbohydrate structures that it will accept.