EFFECT OF HEPARIN AND RELATED GLYCOSAMINOGLYCANS (GAGS) ON THROMBIN-INDUCED PLATELET-AGGREGATION AND RELEASE

We studied in vitro human platelet aggregation by ADP, collagen and thrombin in the presence of various glycosaminoglycans (GAGs: heparin; Hep: heparan sulfate; HS: dermatan sulfate, DeS). Platelet aggregation by ADP and collagen was not significantly modified by GAGs, whereas platelet aggregation by thrombin was completely inhibited. There was no significant difference among the various GAGs in the inhibition of thrombin-induced platelet aggregation. The release of .beta.-TG, PF4 and TXB2 by thrombin was likewise completely blocked in the presence of GAGs. In order to examine the mechanism by which heparins neutralize the effect of thrombin on platelets, we studied the in vitro human washed platelet response to thrombin in the presence of GAGs and in the presence or absence of purified ATIII. In the absence of ATIII, platelet aggregation and release by thrombin was not modified by GAGs. With the addition of purified ATIII, platelet aggregation by thrombin was completely inhibited by Hep and HS, but only slightly by DeS. The release of TXB2, .beta.-TG and, partially, PF4 was likewise blocked in the presence of Hep and HS, but not with DeS. Our results suggest that the mechanism of inhibition of thrombin-induced platelet aggregation and release by Hep and HS is ATIII-dependent, whereas inhibition by DeS depends on inhibitors other than ATIII, probably heparin-cofactor II.