Effect of dermatan sulfate and heparan sulfate on platelet activity compared to heparin

Three different assay systems were studied to determine the effect of dermatan sulfate and heparan sulfate on the activation of platelets. These studies were conducted on an equigravimetric basis for the three glycosaminoglycans. Concentrations were chosen at which differential effects of the three agents could be discerned (10 to 25 micrograms/ml for the HIPA and HIT systems). In the AIPA system where only minimal effects were observed, a higher concentration of 100 micrograms/ml was used. This higher level corresponded to the circulating levels of dermatan sulfate and heparan sulfate required for antithrombotic activity in an animal model (Fareed et al, data not shown). Heparin and saline systems were used as positive and negative controls. Human platelets were studied in a CPDA-1 anticoagulated PRP system. A PRP system was used because it is more physiologic than a washed platelet system. PRP contains all the plasma components and platelet-associated proteins that are present in vivo. One disadvantage, however, is the removal of calcium by the anticoagulant CPDA-1, which may induce a nonphysiologic aberration in the aggregation effect. Overall, these three platelet system studies revealed little to no platelet aggregation response in the presence of dermatan or heparan. Heparin, on the other hand, produced variable but measurable increases, particularly in the heparin-induced thrombocytopenia platelet aggregation system. In the HIPA system (no agonist), only a slight increase was found with heparin, whereas no increase in platelet response was noted with either dermatan or heparan.(ABSTRACT TRUNCATED AT 250 WORDS)