Heparin-induced thrombocytopenic potential of GAG and non-GAG-based antithrombotic agents

We have undertaken these studies of the heparin-like, or glycosaminoglycan, and nonglycosaminoglycan-based antithrombotics in an effort to add to the understanding of the pathophysiologic mechanism of heparin-induced thromboc ytopenia by investigations of how glycosaminoglycan-related agents interact with the heparin-induced thrombocytopenia antibodies. The low molecular we ight heparins, originally thought to be useful alternatives to heparin beca use of their smaller size, show platelet activation and aggregation respons es in platelet heparin-induced thrombocytopenia serum systems (P-selectin e xpression. microparticle formation, serotonin release, platelet aggregation ). Although the molecular mass and sulfation of the heparinoid Lomoparan is similar to that of heparin and low molecular weight heparins, its chemical structure is different and probably is not recognized by the heparin-induc ed thrombocytopenia antibodies. The heparin-related pentasaccharide did not show a positive reaction in any system of platelet activation/aggregation. These studies have shown that the antibodies produced in patients with hep arin-induced thrombocytopenia are reactive to highly sulfated glycosaminogl ycans and nonglycosaminoglycan agents and less dependent on the molecular m ass of these agents; whether the agent is a heparin or nonheparin compound was nut critical. A combination of a moderate sulfation but low molecular m ass in a heparin-like molecule was sufficient to prevent interaction with t he heparin-induced thrombocytopenia antibodies. However, a chemical structu re that is different from heparin (e.g., a heparinoid or a thrombin inhibit or) will also be nonreactive to platelet activation by heparin-induced thro mbocytopenia antibodies.