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 thrombocytopenia by investigations of how glycosaminoglycan-related agents interact with the heparin-induced thrombocytopenia antibodies. The low molecular weight heparins, originally thought to be useful alternatives to heparin because of their smaller size, show platelet activation and aggregation responses in platelet heparin-induced thrombocytopenia serum systems (P-selectin expression, 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-induced 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 heparin-induced thrombocytopenia are reactive to highly sulfated glycosaminoglycans and nonglycosaminoglycan agents and less dependent on the molecular mass of these agents; whether the agent is a heparin or nonheparin compound was not critical. A combination of a moderate sulfation but low molecular mass in a heparin-like molecule was sufficient to prevent interaction with the heparin-induced thrombocytopenia antibodies. However, a chemical structure that is different from heparin (e.g., a heparinoid or a thrombin inhibitor) will also be nonreactive to platelet activation by heparin-induced thrombocytopenia antibodies.
Jeske
W P
WP
Cardiovascular Institute, Loyola University Medical Center, Maywood, IL 60153, USA.
Jay
A M
AM
Haas
S
S
Walenga
J M
JM
D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D006025:Glycosaminoglycans / Q000097:blood / Q000276:immunology*; D006493:Heparin / Q000009:adverse effects* / Q000097:blood / Q000276:immunology*; D006801:Humans; D013921:Thrombocytopenia / Q000097:blood* / Q000139:chemically induced*
D000906:Antibodies; D006025:Glycosaminoglycans; D006493:Heparin