Effects of glycosaminoglycans and protamine chloridrate on platelet aggregation induced by collagen and thrombin

The effects of heparin (HE), dermatan sulfate (DS), heparan sulfate (HS) and protamine chloridrate (PC) on platelet aggregation were studied. Both PC and the three glycosaminoglycans (GAGs) did not influence collagen-induced platelet aggregation. In contrast, all the tested GAGs blocked thrombin-induced platelet aggregation. HE and HS were equivalent and very effective, while DS was also but to a lesser extent. This could be because HE and HS act via both antithrombin III and heparin-cofactor II, whereas DS exerts its action on the latter only. PC, too, inhibited, in a dose-dependent fashion, thrombin-induced platelet aggregation, probably by competing with the thrombin affinity binding sites on the platelet surface. When the GAGs were tested together with PC, HE was shown to be the most effective: on a weight-for-weight basis, an identical amount of PC was unable to counteract the inhibitory effect of HE, while it partially reversed those of DS and HS. A full reversal of the inhibitory effect of DS and HS was never observed, in spite of adding increasing amounts of PC. It seems likely that plasma components may preserve the bindings of such GAGs with their cofactors.